CN103070862A

CN103070862A - Application of Harmine derivative to preparation of antibacterial medicine

Info

Publication number: CN103070862A
Application number: CN2012104258850A
Authority: CN
Inventors: 王子厚; 武嘉林; 张淑华; 曹日晖; 马芹; 莫非; 张姝; 范文玺; 孙洁; 胡伏莲; 周凡; 慕春海
Original assignee: HUASHIDAN PHARMACEUTICAL RESEARCH Co Ltd XINJIANG
Current assignee: HUASHIDAN PHARMACEUTICAL RESEARCH Co Ltd XINJIANG; Xinjiang Huashidan Pharmaceutical Res Co Ltd
Priority date: 2011-10-25
Filing date: 2012-10-25
Publication date: 2013-05-01
Also published as: CN111012779A; WO2014063477A1

Abstract

The invention discloses application of a Harmine derivative to preparation of antibacterial medicines. The bacteria is selected from Acinetobacter, Bacillus, Campylobacter, Chlamydia, Chlamydia trachomatis, Clostridium, Citrobacter, Escherichia, enterohemorrhagic escherichia coli, enteric bacteria, Enterococcus, Francisella, Haemophilus, helicobacter, Klebsiella Bacillus, Lester monocytogenes, Moraxella, Mycobacterium, Neisseria, proteus, Pseudomonas, Salmonella, shewanella oneidensis, Shigella, Stenotrophomonas, Staphylococcus, Streptococcus and Yersinia.

Description

The application of Yageine derivates in the preparation antibacterials

Technical field

The present invention relates to the application of Yageine derivates in the preparation antibacterials; Belong to medical technical field.

Background technology

Yageine (Harmine) is that (molecular formula is C to B-carboline for a member of Alkaloid family of β-carboline), its chemistry 7-methoxyl group by name-1-methyl-9H-pyrroles [3,4-b] indole ₁₃H ₁₂N ₂O, molecular weight 212.25,261 ℃ of fusing points, chemical structural formula is as follows:

Yageine and analog thereof are distributed widely in nature.Since being separated to first the harmine alkaloid compound, people have carried out the study on the synthesis of a large amount of harmine alkaloid compounds, according to incompletely statistics, up to the present, people have reported about harmine alkaloid compound more than 300, and new harmine alkaloid compound is still in continuous increase.

The harmine alkaloid compound has significant anti-tumor activity, but obvious central nervous system toxicity is also arranged.Its anti tumor activity in vitro result of the test shows that the banisterine compounds has obvious inhibitory action to the tumor cell of the multiple In vitro culture such as cervical cancer Hela cells, S-180 cultured cell in vitro, hepatocarcinoma BEL-7402, Gastric Cancer MGC-803, nasopharyngeal carcinoma CNE2, breast carcinoma MA782 ' 5S, leukemia K 562; Anti-tumor in vivo activity test result shows that the mixed biologic alkali that extracts in total alkaloid of harmaline, the Herba pegani harmalae plant has significant curative effect to mice S-180, reticulum cell sarcoma L2, rat liver cancer, with cisplatin, amycin coupling obvious synergism is arranged; Yet the toxicity main manifestations of banisterine and derivant thereof is nervous system toxicity.Acute toxicity shows as nervous system first excited (trembling, erect tail, convulsions), rear inhibition, and last dead, dead animal can not recover normal in administration next day.Subacute toxicity test prompting total alkaloid of harmaline there is no overt toxicity to hemopoietic system, immune system, reproductive system, and long-term toxic and side effects is not remarkable yet, and its toxicity target organ is kidney.

Although present yageine and analog thereof have clear and definite anti-tumor activity, but clear and definite nervous system side effect is arranged also, also do not have a kind of existing high anti-tumor activity, nervous system toxicity again low chemical compound can be used for clinically as cancer therapy drug.Do not report the antibacterial activity of Yageine derivates in the prior art.

Summary of the invention

The technical problem to be solved in the present invention provides the new antibacterials of a class, i.e. Yageine derivates.

Described Yageine derivates is as follows:

Among the present invention, as be not particularly limited, described substituent group is one or more.

9 replace I

1、

R ⁹Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl-CO-(CH) _j-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH) of O or S _K-and i be selected from the integer of 1-6;

Replace or non-substituted five-hexa-atomic aryl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Replace or non-substituted contain 1-4 and be selected from N, the substituent group on heteroatomic five-six membered heteroaryl of O or S is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Replace or non-substituted C1-10 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group.

Preferred R ⁹Be selected from hydrogen; replace or non-substituted C1-8 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-6 straight or branched alkylthio group; C1-6 alcoxyl C1-6 alkyl; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-6; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-4, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-4;

Replace or non-substituted five-hexa-atomic aryl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

Replace or non-substituted contain 1-4 and be selected from N, the substituent group on heteroatomic five-six membered heteroaryl of O or S is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

Replace or non-substituted C1-4 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group.Preferred R ⁹Be selected from hydrogen, replacement or non-substituted C1-8 straight or branched alkyl, replacement or non-substituted phenyl, replacement or non-substituted phenyl (CH ₂) _f-and f be selected from the integer of 1-4; Replace or non-substituted phenyl-CO-CH ₂-and f be selected from the integer of 1-4;

Replace or non-substituted phenyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

Replace or non-substituted C1-8 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group.

Most preferred R ₉Be selected from CH ₃, C ₂H ₅, n-C ₃H ₇, CH (CH ₃) ₂, n-C ₄H ₉, CH ₂CH (CH ₃) ₂, C ₆H ₁₃,

C ₈H ₁₇、CH ₂CH ₂OH、

C ₆H ₅、C ₆H ₄(p-OCH ₃)、C ₆H ₄(p-OH)、C ₆H ₄(p-F)

CH ₂C ₆H ₅、(CH ₂) ₃C ₆H ₅、CH ₂C ₆F ₅、CH ₂CO?C ₆H ₅

2, preferred formula I chemical compound is including but not limited to the chemical compound (9 is alkyl) of formula IA

R ⁹Be selected from hydrogen, replacement or non-substituted C1-8 straight or branched alkyl;

3, preferred formula I chemical compound is including but not limited to the chemical compound (the 9-position is phenyl) of formula IB

R ₉₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

N is selected from the integer of 1-6;

M is selected from the integer of 1-6,

4, most preferred formula I chemical compound is selected from following group:

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ₉
			10	H-0-1	H
11	H-0-2	CH ₃
			12	H-0-3	C ₂H ₅
13	H-0-4	n-C ₄H ₉
			14	H-0-5	CH ₂C ₆H ₅

5,1,3 replaces II

R ¹Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; amido; replace or non-substituted C1-10 straight or branched alkylamino radical; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; replace or non-substituted C1-10 straight or branched alkyl amide base; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; CH=N-O-C1-10 straight or branched alkyl; CH=N-NHC (S) NH ₂, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 2-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 2-6, replace or five non-substituted or hexa-atomic aryl-CO-(CH) _J-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH) of O or S _K-and i be selected from the integer of 1-6;

Preferred R ¹Be selected from hydrogen; replace or non-substituted C1-6 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-6 straight or branched alkylthio group; amido; replace or non-substituted C1-6 straight or branched alkylamino radical; C1-6 alcoxyl C1-6 alkyl; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; replace or non-substituted C1-6 straight or branched alkyl amide; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; CH=N-O-C1-6 straight or branched alkyl; CH=N-NHC (S) NH ₂, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 2-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 2-6, replace or five non-substituted or hexa-atomic aryl-CO-(CH ₂) _j-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH of O or S ₂) _K-and i be selected from the integer of 1-6;

Replace or non-substituted C1-6 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group.

Preferred R ¹Be selected from hydrogen; replace or non-substituted C1-6 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; amido; replace or non-substituted C1-6 straight or branched alkylamino radical; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; replace or non-substituted C1-6 straight or branched alkyl amide; carbamoyl; the alkene of C2-6; halogen; nitro; cyano group; CH=N-O-C1-6 straight or branched alkyl; CH=N-NHC (S) NH ₂, replacement or non-substituted phenyl, replacement or non-substituted pyridine radicals, replacement or non-substituted phenyl-CH ₂-and f be selected from integer, replacement or the non-substituted phenyl-(CH) of containing of 1-6 ₂-and g be selected from the integer of 2-6;

Replacement or non-substituted phenyl, the substituent group on the pyridine radicals are selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Most preferred R ¹Be selected from CH ₃, C ₂H ₅, n-C ₃H ₇, CH (CH ₃) ₂, n-C ₄H ₉, CH ₂CH (CH ₃) ₂,

CH ₂CH ₂OH、

NHCH ₂CH ₂NH ₂、CHO、COOH、COOCH ₂CH ₃、CONH-CH ₂CH ₂NH ₂；

CH=N-OCH ₃、CH=N-NHC(S)NH ₂；

C ₆H ₅、C ₆H ₄(p-OCH ₃)、C ₆H ₄(p-OH)、C ₆H ₄(m-Cl)、3-C ₅H ₅N

CH ₂C ₆H ₅、CH=CH-C ₆H ₄(p-OCH ₃)、CH=CH-C ₆H ₄(p-NO ₂)、

R ³Be selected from hydrogen, aldehyde radical, replacement or non-substituted C1-10 straight or branched alkanoyl, carboxyl, replacement or non-substituted C1-10 straight or branched alkyl-ester group, replacement or non-substituted C1-10 straight or branched alkanoyloxy, replacement or non-substituted C1-10 straight or branched alkyl-amide groups, replacement or non-substituted C1-10 straight or branched alkyl-amine acyl group, carbamoyl, CH=NNHC (S) NH2

Replace or five non-substituted or hexa-atomic aryl--ester group, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-ester group of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6,

Preferred R ³Be selected from hydrogen, aldehyde radical, replacement or non-substituted C1-6 straight or branched alkanoyl, carboxyl, replacement or non-substituted C1-6 straight or branched alkyl-ester group, replacement or non-substituted C1-6 straight or branched alkanoyloxy, replacement or non-substituted C1-6 straight or branched alkyl-amide groups, replacement or non-substituted C1-6 straight or branched alkyl-amine acyl group, carbamoyl, CH=NNHC (S) NH ₂

Most preferred R ³¹Be selected from

CH ₃、C ₂H ₅、n-C ₄H ₉、NH ₂、CH ₂OH、CH ₂OOCCH ₃

COOH、

COOCH ₃、COOC ₂H ₅、COOn-C ₄H ₉、COONH ₂、COOC ₆H ₅；

NHCOCH ₃、NHCOC ₂H ₅、NHCOn-C ₄H ₉、NHCOCH ₂CH ₂NH ₂；

CONHCH ₃、CONHC ₂H ₅、CONHn-C ₄H ₉、CONHOCH ₃、CONHOC ₂H5 _、CONHNH ₂、

CONHCH ₂CH ₂NH ₂、CONHCH ₂CH ₂OH；

NHCOOCH ₃、NHCOOC ₂H ₅、

CHO、CH=NNHC(S)NH ₂、

6, preferred formula II chemical compound is including but not limited to the chemical compound of formula IIA, (the 3-position is acid)

7, preferred formula IIA chemical compound is including but not limited to the chemical compound of formula IIAa,

Preferred R ¹Be selected from hydrogen, replacement or non-substituted C1-6 straight or branched alkyl;

8, preferred formula IIA chemical compound is including but not limited to the chemical compound of formula IIAb,

R ₁₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl.

N is selected from the integer of 1-6;

9, the 3-position is ester (IIB) (3-position Arrcostab, benzyl ester)

Preferred R ₃₁Be selected from and replace or non-substituted C1-6 straight or branched alkyl, replacement or non-substituted five or six membered heteroaryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6,

10

Preferred R ¹Be selected from hydrogen; replace or non-substituted C1-6 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; amido; replace or non-substituted C1-6 straight or branched alkylamino radical; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; replace or non-substituted C1-6 straight or branched alkyl amide; carbamoyl; the alkene of C2-6; halogen; nitro; cyano group; CH=N-O-C1-6 straight or branched alkyl; CH=N-NHC (S) NH ₂,

11

R ₃₁Be selected from and replace or non-substituted C1-6 straight or branched alkyl;

With further

12

R ₃₁₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

13

The 143-position is alcohol (IIC)

15

16

R ₁₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

N is selected from the integer of 1-6;

17, the 3-position is aldehyde (IID)

18、

19、

N is selected from the integer of 1-6;

20, the 3-position is thiourea (IIE)

21

22

N is selected from the integer of 1-6;

23

The 3-position is amide (IIF)

Preferred R ₃₁Be selected from and replace or non-substituted C1-6 straight or branched alkyl, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6,

24

Preferred R ₃₁Be selected from and replace or non-substituted C1-6 straight or branched alkyl, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S-, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6,

25

N is selected from the integer of 1-6;

The chemical compound of 1,3 replacement of most preferred chemical compound is selected from

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ¹	R ³¹
				59	H-1-5	CH ₃	C ₂H ₅
60	H-1-6	C ₂H ₅	C ₂H ₅
				61	H-1-7	n-C ₃H ₇	C ₂H ₅
62	H-1-1	C ₆H ₅	CH ₃
				63	H-1-3	C ₆H ₄(p-OCH ₃)	CH ₃
64	H-1-2	C ₆H ₄(p-OH)	CH ₃

The compound III of 1,9 replacement

Chemical compound shown in the preferred formula III is shown in IIIA

Preferred R ¹Be selected from hydrogen, replacement or non-substituted C1-6 straight or branched alkyl, preferred R ⁹Be selected from hydrogen; replace or non-substituted C1-8 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-6 straight or branched alkylthio group; C1-6 alcoxyl C1-6 alkyl; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-6; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-4, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-4;

Replace or non-substituted C1-4 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group.

Chemical compound shown in the preferred formula III is shown in IIIB

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III is shown in IIIC

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III is shown in IIID

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III A is shown in IIIAa

Preferred R ¹Be selected from hydrogen, replacement or non-substituted C1-8 straight or branched alkyl.

Preferred R ⁹Be selected from hydrogen, replacement or non-substituted C1-8 straight or branched alkyl.

Chemical compound shown in the preferred formula III A is shown in IIIAb

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula III B is shown in IIIBa

R ₁₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula III B is shown in IIIBb

M is selected from the integer of 1-6,

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III C is shown in IIICa

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III C is shown in IIICb

M is selected from the integer of 1-6,

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III D is shown in IIIDa

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula III D is shown in IIIDb

M is selected from the integer of 1-6,

N is selected from the integer of 1-6; Most preferred chemical compound is selected from following group: the preparation of following chemical compound is open in WO2004/106335

No	Code name	R ₉
			15	H-3-83	H
16	H-3-85	CH ₃

[0284]?

17	H-3-86	C ₂H ₅
			18	H-2-31	CH(CH ₃) ₂
19	H-3-87	n-C ₄H ₉
			?	?	?
20	H-3-82	CH ₂C ₆H ₅
			21	H-3-81	CH ₂C ₆F ₅
22	H-3-89	(CH ₂) ₃C ₆H ₅

3,9 replace IV

R ³Be selected from hydrogen, aldehyde radical, replacement or non-substituted C1-10 straight or branched alkanoyl, carboxyl, replacement or non-substituted C1-10 straight or branched alkyl-ester group, replacement or non-substituted C1-10 straight or branched alkanoyloxy, replacement or non-substituted C1-10 straight or branched alkyl-amide groups, replacement or non-substituted C1-10 straight or branched alkyl-amine acyl group, carbamoyl, CH=NNHC (S) NH ₂

Chemical compound shown in the preferred formula IV is shown in IVA

Chemical compound shown in the preferred formula IVA is shown in IVAa

R ⁹Be selected from hydrogen, replacement or non-substituted C1-10 straight or branched alkyl,

Chemical compound shown in the preferred formula IVA is shown in IVAb

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula IV is shown in IVB

Chemical compound shown in the preferred formula IVB is shown in IVBa

Preferred R ₃₁Be selected from replace or non-substituted C1-6 straight or branched alkyl, replacement or non-substituted phenyl,

Replace or non-substituted phenyl is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Chemical compound shown in the preferred formula IVB is shown in IVBb

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula IVBa is shown in IVBa1

R ₃₁₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

Chemical compound shown in the preferred formula IVBb is shown in IVBb1

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula IV is shown in IVC

Chemical compound shown in the preferred formula IVC is shown in IVCa

Chemical compound shown in the preferred formula IVC is shown in IVCb

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula IV is shown in IVD

Chemical compound shown in the preferred formula IVD is shown in IVDa

Chemical compound shown in the preferred formula IVD is shown in IVDb

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula IV is shown in IVE

Chemical compound shown in the preferred formula IVE is shown in IVEa

Chemical compound shown in the preferred formula IVE is shown in IVEb

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula IV is shown in IVF

Chemical compound shown in the preferred formula IVF is shown in IVFa

R ₃₁Be selected from replace or non-substituted C1-6 straight or branched alkyl, replacement or non-substituted phenyl,

Chemical compound shown in the preferred formula IVF is shown in IVFb

M is selected from the integer of 1-6,

The chemical compound of most preferred 3,9 replacements preferably is selected from following group:

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ³	R ⁹
				91	H-3-37	COOC ₆H ₅	CH ₂C ₆H ₅
92	H-3-26	CH ₂OH	CH ₂C ₆H ₅
				93	H-3-27	CH ₂OOCCH ₃	CH ₂C ₆H ₅

Open in WO2004/106335 by the sort preparation of following chemical compound of structure

No	Code name	R ³	R ⁹
				23	H-3-23	NH ₂	H
24	H-3-67	NHCO-OCH ₃	H
				25	H-3-29	NHCO-OC ₂H ₅	H
32	H-3-34	NHCO-OCH ₃	C ₂H ₅
				33	H-3-35	NHCO-OC ₂H ₅	C ₂H ₅
34	H-3-30	NHCO-OC ₂H ₅	CH ₂C ₆H ₅
				?	?	?	?
26	H-3-22	CONH-NH ₂	H
				27	H-3-11	CONH-CH ₂CH ₂NH ₂	H
30	H-3-36	CONH-NH ₂	C ₂H ₅
				31	H-3-28	CONH-NH ₂	CH ₂C ₆H ₅
?	?	?	?
				28	H-3-24	CH ₂OH	H
29	H-3-25	CH ₂OOCCH3	H

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ³¹	R ⁹
				35	H-3-3	CH ₃	H
36	H-3-8	C ₂H ₅	H
				37	H-3-17	n-C ₄H ₉	H
38	H-3-5	CH ₃	CH ₃
				39	H-3-6	CH ₃	C ₂H ₅
40	H-3-14	CH ₃	n-C ₄H ₉
				41	H-3-12	CH ₃	CH ₂C ₆H ₅
42	H-3-13	C ₂H ₅	CH ₃
				43	H-3-9	C ₂H ₅	C ₂H ₅
44	H-3-16	C ₂H ₅	n-C ₄H ₉
				45	H-3-7	C ₂H ₅	CH ₂C ₆H ₅
46	H-3-41	C ₂H ₅	CH ₂C ₆F ₅
				47	H-3-38	C ₂H ₅	(CH ₂) ₃C ₆H ₅
48	H-3-18	n-C ₄H ₉	CH ₃
				49	H-3-19	n-C ₄H ₉	C ₂H ₅

[0414]?

50	H-3-20	n-C ₄H ₉	n-C ₄H ₉
				51	H-3-21	n-C ₄H ₉	CH ₂C ₆H ₅

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ₉
			52	H-3-4	H
53	H-3-31	CH ₃
			54	H-3-32	C ₂H ₅
55	H-3-33	n-C ₄H ₉
			56	H-3-15	CH ₂C ₆H ₅
57	H-3-42	CH ₂C ₆F ₅
			58	H-3-39	(CH ₂) ₃C ₆H ₅

The chemical compound (V) of 1,3,9 replacements

R ¹Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; amido; replace or non-substituted C1-10 straight or branched alkylamino radical; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; replace or non-substituted C1-10 straight or branched alkyl amide base; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; CH=N-O-C1-10 straight or branched alkyl; CH=N-NHC (S) NH2; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 2-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 2-6, replace or five non-substituted or hexa-atomic aryl-CO-(CH) _j-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH) of O or S _K-and i be selected from the integer of 1-6;

R ⁹Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-6, replace or integer that non-substituted five or hexa-atomic aryl-CO-(CH) j-and j are selected from 1-6, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH) of O or S _K-and i be selected from the integer of 1-6;

Chemical compound shown in the preferred formula V is shown in VA

Chemical compound shown in the preferred formula V is shown in VB

Chemical compound shown in the preferred formula V is shown in VC

Chemical compound shown in the preferred formula V is shown in VD

Chemical compound shown in the preferred formula V is shown in VE

Chemical compound shown in the preferred formula V is shown in VF

R ₃₁Be selected from and replace or non-substituted C1-6 straight or branched alkyl, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S-, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6,

Most preferred 1,3,9 chemical compounds that replace (V) are selected from following group:

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ¹	R ⁹
				78	H-3-45	CH ₃	CH ₃
79	H-3-47	CH ₃	C ₂H ₅
				80	H-3-80	CH ₃	n-C ₄H ₉
81	H-3-49	CH ₃	CH ₂C ₆H ₅
				82	H-3-50	CH ₃	(CH ₂) ₃C ₆H ₅
83	H-3-52	CH ₃	CH ₂C ₆F ₅
				84	H-3-69	CH ₃	CH ₂CO?C ₆H ₅

[0475]?

85	H-3-54	n-C ₃H ₇	CH ₃
				86	H-3-56	n-C ₃H ₇	C ₂H ₅
87	H-3-58	n-C ₃H ₇	CH ₂C ₆H ₅
				88	H-3-59	n-C ₃H ₇	(CH ₂) ₃C ₆H ₅
89	H-3-61	C ₆H ₅	CH ₃
				90	H-3-63	C ₆H ₅	C ₂H ₅

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ¹	R ³¹	R ⁹
					65	H-3-44	CH ₃	C ₂H ₅	CH ₃
66	H-3-46	CH ₃	C ₂H ₅	C ₂H ₅
					67	H-3-88	CH ₃	C ₂H ₅	n-C ₄H ₉
68	H-3-48	CH ₃	C ₂H ₅	CH ₂C ₆H ₅
					69	H-3-64	CH ₃	C ₂H ₅	(CH ₂) ₃C ₆H ₅
70	H-3-51	CH ₃	C ₂H ₅	CH ₂C ₆F ₅
					71	H-3-68	CH ₃	C ₂H ₅	CH ₂COC ₆H ₅
72	H-3-53	n-C ₃H ₇	C ₂H ₅	CH ₃
					73	H-3-55	n-C ₃H ₇	C ₂H ₅	C ₂H ₅
74	H-3-57	n-C ₃H ₇	C ₂H ₅	CH ₂C ₆H ₅
					75	H-3-65	n-C ₃H ₇	C ₂H ₅	(CH ₂) ₃C ₆H ₅
76	H-3-60	C ₆H ₅	C ₂H ₅	CH ₃
					77	H-3-62	C ₆H ₅	C ₂H ₅	C ₂H ₅

The preparation of stating chemical compound is open in CN101139347A

Numbering	Code name	R ³¹	R ⁹
				29	H-2-83	C ₂H ₅	H
30	H-2-50	C ₂H ₅	(CH ₂) ₃C ₆H ₅

[0482]The preparation of following chemical compound is open in CN101429198A

No	Code name	R ¹	R3	R9
					49	H-2-123	CH ₃	CH ₂OH	n-C ₄H ₉
50	H-2-121	CH ₃	CH ₂OH	CH ₂C ₆H ₄(p-F)
					51	H-3-26	H	CH ₂OH	CH ₂C ₆H ₅
52	H-2-131	H	CH ₂OH	(CH ₂) ₃C ₆H ₅
					54	H-2-138	CH ₃	CHO	n-C ₄H ₉
55	H-2-133	CH ₃	CHO	CH ₂C ₆H ₄(p-F)
					56	H-2-118	H	CHO	CH ₂C ₆H ₅
57	H-2-141	H	CHO	(CH ₂) ₃C ₆H ₅
					59	S-9	CH ₃	CH＝NNHC(S)NH ₂	n-C ₄H ₉
60	S-11	CH ₃	CH＝NNHC(S)NH ₂	CH ₂C ₆H ₄(p-F)
					61	S-2	H	CH＝NNHC(S)NH ₂	CH ₂C ₆H ₅
62	S-6	H	CH＝NNHC(S)NH ₂	(CH ₂) ₃C ₆H ₅

The preparation of following chemical compound is open in CN101429198A

No	Code name	R ¹	R ³	R ⁹
					42	H-2-82	C ₆H ₃(3，4，5-trimethoxy)	H	H
43	H-2-98	C ₆H ₃(3，4，5-trimethoxy)	H	n-C ₄H ₉
					44	H-2-83	C ₆H ₃(3，4，5-trimethoxy)	COOC ₂H ₅	H
45	H-2-92	C ₆H ₃(3，4，5-trimethoxy)	COOC ₂H ₅	n-C ₄H ₉
					46	H-2-95	C ₆H ₃(3，4，5-trimethoxy)	COOH	n-C ₄H ₉
47	H-2-103	C ₆H ₃(3，4，5-trimethoxy)	CONHCH ₂CH ₂OH	n-C ₄H ₉
					48	H-2-148	C ₆H ₃(3，4，5-trimethoxy)	CH ₂OH	n-C ₄H ₉
53	H-2-144	C6H3(3，4，5-trimethoxy)	CHO	n-C4H9
					58	S-15	C ₆H ₃(3，4，5-trimethoxy)	CH＝NNHC(S)NH ₂	n-C ₄H ₉

1,7,9 replace (VI)

R ⁷Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-6;

Chemical compound shown in the preferred formula VI is shown in VIA

Preferred R ⁷Be selected from hydrogen; replace or non-substituted C1-6 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-6 straight or branched alkylthio group; C1-6 alcoxyl C1-6 alkyl; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-6; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-4, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer of 1-4, replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-4;

Chemical compound shown in the preferred formula VI is shown in VIB

Preferred R ⁷¹Hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Chemical compound shown in the preferred formula VIA is shown in VIAa

R ¹Being selected from replacement or non-substituted C1-8 straight or branched alkyl, substituent group is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

R ₇₁Being selected from replacement or non-substituted C1-8 straight or branched alkoxyl base, substituent group is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

R ⁹Be selected from hydrogen, replacement or non-substituted C1-8 straight or branched alkyl, replacement or non-substituted phenyl, replacement or non-substituted phenyl (CH ₂) _f-and f be selected from the integer of 1-4; Replace or non-substituted phenyl-CO-(CH) _K-and K be selected from the integer of 1-4; Replace or non-substituted phenyl, replacement or non-substituted phenyl (CH) _i-and i be selected from the integer of 1-4;

Replace or non-substituted C1-8 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group;

Chemical compound shown in the preferred formula VIA is shown in VIAb

R ₇₁Be selected from and replace or non-substituted C1-8 straight or branched alkoxyl, substituent group is selected from, hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIA is shown in VIAc

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIAa is shown in VIAa1

R ₇₁Be selected from: replace or non-substituted C1-6 alkoxyl; Substituent group is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

R ⁹Being selected from replacement or non-substituted C1-8 straight or branched alkyl, substituent group is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

K is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIAa is shown in VIAa2

M is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIAb is shown in VIAb1

R ₉Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIAb is shown in VIAb2

M is selected from the integer of 1-6,

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIAc is shown in VIAc1

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIAc is shown in VIAc2

R ₉₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

M is selected from the integer of 1-6,

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIB is shown in VIBa

R ₇₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

K is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIB is shown in VIBb

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIB is shown in VIBc

K is selected from the integer of 1-6,

N is selected from the integer of 1-6,

Chemical compound shown in the preferred formula VIBa is shown in VIBa1

R ₇₁Be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

K is selected from the integer of 1-6;

Chemical compound shown in the preferred formula VIBa is shown in VIBa2

K is selected from the integer of 1-6,

M is selected from the integer of 1-6;

Chemical compound shown in the preferred formula VIBb is shown in VIBb1

K is selected from the integer of 1-6,

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula VIBb is shown in VIBb2

K is selected from the integer of 1-6,

M is selected from the integer of 1-6,

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula VIC is shown in VIBc1

K is selected from the integer of 1-6,

N is selected from the integer of 1-6;

Chemical compound shown in the preferred formula VIC is shown in VIBc2

K is selected from the integer of 1-6,

M is selected from the integer of 1-6,

N is selected from the integer of 1-6.

Most preferred 1,7,9 substituted compounds (VI) are selected from following group:

The preparation of following chemical compound is open in WO2004/106335

No	Code name	R ¹	R ⁷	R ⁹
					1	H-9-6	CH ₃	OCH ₃	H
2	H-9-5	CH ₃	OCH ₃	CH ₃
					3	H-9-1	CH ₃	OCH ₃	C ₂H ₅
4	H-9-2	CH ₃	OCH ₃	CH ₂CH ₂OH
					5	H-2-29	CH ₃	OCH ₃	CH ₂CH(CH ₃) ₂
6	H-9-4	CH ₃	OCH ₃	n-C ₄H ₉
					7	H-9-3	CH ₃	OCH ₃	CH ₂C ₆H ₅
8	H-3-43	CH ₃	OCH ₃	CH ₂C ₆F ₅
					9	H-3-66	CH ₃	OCH ₃	(CH ₂) ₃C ₆H ₅

The preparation of following chemical compound is open in CN101139347A

No	Code name	R ¹	R ⁷	R ⁹
					10	H-2-33	CH ₃	OH	(CH ₂) ₃C ₆H ₅
11	H-2-38	CH ₃	OCH(CH ₃) ₂	(CH ₂) ₃C ₆H ₅
					12	H-2-34	CH ₃	OC ₄H ₉	(CH ₂) ₃C ₆H ₅
13	H-2-42	CH ₃	OCH ₂CH(CH ₃) ₂	(CH ₂) ₃C ₆H ₅
					14	H-2-39	CH ₃	OCH(CH ₂CH ₃) ₂	(CH ₂) ₃C ₆H ₅
15	H-2-41	CH ₃	OCH ₂CH＝C(CH ₃) ₂	(CH ₂) ₃C ₆H ₅
					16	H-2-35	CH ₃	OC ₈H ₁₇	(CH ₂) ₃C ₆H ₅
17	H-2-36	CH ₃	OCH ₂C ₆H ₅	(CH ₂) ₃C ₆H ₅
					18	H-2-40	CH ₃	OCH ₂C ₆F ₅	(CH ₂) ₃C ₆H ₅
19	DH-278	CH ₃	OCH ₂C ₆H ₄(m-Cl)	(CH ₂) ₃C ₆H ₅
					20	DH-279	CH ₃	OCH ₂C ₆H ₄(p-F)	(CH ₂) ₃C ₆H ₅
21	H-2-37	CH ₃	O(CH ₂) ₃C ₆H ₅	(CH ₂) ₃C ₆H ₅
					28	DH-176	C ₆H ₄(m-Cl)	H	(CH ₂) ₃C ₆H ₅

[0644]The preparation of following chemical compound is open in CN101429198A

No	Code name	R ¹	R ⁷	R ⁹
					1	H-2-17	CH ₃	OH	C ₂H ₅
2	H-2-18	CH ₃	OH	n-C ₄H ₉
					3	H-2-62	CH ₃	OH	CH ₂CH(CH ₃) ₂
4	H-2-48	CH ₃	OCH ₂CH(CH ₃) ₂	C ₂H ₅
					5	H-2-52	CH ₃	OCH ₂C ₆H ₅	C ₂H ₅
6	H-2-50	CH ₃	O(CH ₂) ₃C ₆H ₅	C ₂H ₅
					7	H-2-43	CH ₃	OCH ₂CH(CH ₃) ₂	n-C ₄H ₉
8	H-2-26	CH ₃	OCH ₂CHOHCF ₃	n-C ₄H ₉
					9	H-2-25	CH ₃	OCH ₂C ₆H ₅	n-C ₄H ₉
10	H-2-63	CH ₃	OC ₄H ₉	CH ₂CH(CH ₃) ₂
					11	H-2-67	CH ₃	OC ₁₀H ₂₁	CH ₂CH(CH ₃) ₂
12	H-2-68	CH ₃	O(CH ₂) ₃C ₆H ₅	CH ₂CH(CH ₃) ₂
					21	H-2-84	CO-OCH ₂CH ₃	H	H
22	H-2-164	CO-OCH ₂CH ₃	H	n-C ₄H ₉
					23	H-2-88	CO-OH	H	n-C ₄H ₉
24	Y-17	CHO	H	(CH ₂) ₃C ₆H ₅
					25	Y-13	CH＝N-NHC(S)NH ₂	H	(CH ₂) ₃C ₆H ₅
26	Y-12	CH＝N-OCH ₃	H	(CH ₂) ₃C ₆H ₅
					27	D-5	CH＝CH-C ₆H ₄(p-OCH ₃)	H	n-C ₄H ₉
28	D-7	CH＝CH-C ₆H ₄(p-OCH ₃)	H	(CH ₂) ₃C ₆H ₅
					29	D-9	CH＝CH-C ₆H ₄(p-OCH ₃)	OC ₄H ₉	(CH ₂) ₃C ₆H ₅
30	D-17	CH＝CH-C ₆H4 ₍p-NO ₂)	OC ₄H ₉	(CH ₂) ₃C ₆H ₅
					35	DH-326	3-C ₅H ₅N (3-pyridine radicals)	H	n-C ₄H ₉
36	DH-320	3-C ₅H ₅N (3-pyridine radicals)	H	CH ₂C ₆H ₅
					37	M3	CONH-CH ₂CH ₂NH ₂	H	(CH ₂) ₃C ₆H ₅
38	N3	NHCH ₂CH ₂NH ₂	H	n-C ₄H ₉
					39	N4	NHCH ₂CH ₂NH ₂	H	(CH ₂) ₃C ₆H ₅

Among the present invention, if substituent position is unqualified, described substituent group can be connected with parent nucleus in the position of any appropriate, if substituent number is unqualified, described substituent group can be one or more.

Compound quaternary ammonium salt class of the present invention also shows good antibacterial activity, and this class quaternary ammonium salt can have by the easily preparation on the basis of aforesaid compound of present technology, and preferred quaternary ammonium salt is as follows:

9 replace I

X is selected from any ion of energy quaternary ammonium ion salify;

R ²Be selected from and replace or non-substituted C1-10 straight or branched alkyl, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6;

1 is alkyl, IA

X is selected from acid radical anion, organic acid anion, the halogen anion of mineral acid;

R ₂Be selected from and replace or non-substituted C1-6 straight or branched alkyl, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-4;

R11 is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

The 1-position is phenyl, IB

R ₉₁Substituent group is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Preferred chemical compound is selected from

1,3 replaces II

X is selected from any ion of energy quaternary ammonium ion salify;

The 3-position is ester (IIA)

Preferred chemical compound is selected from

1,9 replaces III

R ¹Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; amido; replace or non-substituted C1-10 straight or branched alkylamino radical; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; replace or non-substituted C1-10 straight or branched alkyl amide base; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; CH=N-O-C1-10 straight or branched alkyl; CH=N-NHC (S) NH ₂, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 2-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _iAnd i is selected from the integer of 2-6, replaces or five non-substituted or hexa-atomic aryl-CO-(CH) _j-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH) of O or S _K-and i be selected from the integer of 1-6;

X is selected from any ion of energy quaternary ammonium ion salify;

The 1-position is alkyl, IIIA

The 1-position is phenyl, IIIB

1-position thiophene, IIIC

1-position pyrroles, IIID

The chemical compound salt of most preferred 3,9 replacements is selected from following group:

The salt that 1,3,9-position replaces

X is selected from any ion of energy quaternary ammonium ion salify;

The salt (S-V) of most preferred 1,3,9 replacements is selected from following chemical compound

The preparation of following chemical compound is open in WO2004/106335

No

Code name

R ¹

R ²

R ³

R ⁹

X

94

H-2-1

H

CH ₂C ₆H ₅

COOC ₂H ₅

CH ₂C ₆H ₅

Br

95

H-2-5

H

CH ₃

H

CH ₃

I

96

H-2-4

H

CH ₂CH ₃

H

CH ₂CH ₃

I

97

H-2-3

H

CH ₂C ₆H ₅

H

CH ₂C ₆H ₅

Br

98

H-3-84

CH ₃

CH ₂C ₆H ₅

H

CH ₂C ₆H ₅

Br

The salt (S-VI) of 1,7,9 replacements

X is selected from any ion of energy quaternary ammonium ion salify;

Chemical compound shown in the preferred formula S-VI is shown in S-VIA

Preferred R ₁Be selected from hydrogen; replace or non-substituted C1-6 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-6 straight or branched alkylthio group; amido; replace or non-substituted C1-6 straight or branched alkylamino radical; C1-6 alcoxyl C1-6 alkyl; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; replace or non-substituted C1-6 straight or branched alkyl amide; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; CH=N-O-C1-6 straight or branched alkyl; CH=N-NHC (S) NH ₂, replacement or non-substituted five or hexa-atomic aryl, replacement or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 2-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 2-6, replace or five non-substituted or hexa-atomic aryl-CO-(CH ₂) _j-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH of O or S ₂) _K-and i be selected from the integer of 1-6;

R ²Be selected from and replace or non-substituted C1-6 straight or branched alkyl, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-4 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-4;

Chemical compound shown in the preferred formula S-VI is shown in S-VIB

Chemical compound shown in the preferred formula S-VIA is shown in S-VIAa

K is selected from the integer of 1-6,

R ₂Be selected from alkyl, replacement or non-substituted phenyl, replacement or the non-substituted phenyl (CH of C1-6 ₂) _f-and f be selected from the integer of 1-4; Replace or non-substituted phenyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

X is selected from acid radical anion, organic acid anion, the halogen anion of mineral acid

Described mineral acid is selected from sulphuric acid, phosphoric acid, hydrochloric acid, hydrobromic acid, nitric acid, sulfurous acid, valeric acid, methanesulfonic acid, ethyl sulfonic acid, toluenesulfonic acid, salicylic acid, benzoic acid; Described organic acid is selected from formic acid, acetic acid, malonic acid, lactic acid, cinnamic acid, succinic acid, oxalic acid, citric acid, maleic acid, fumaric acid, malic acid, mandelic acid, tartaric acid, sulfonic acid.Chemical compound shown in the preferred formula S-VIA is shown in S-VIAb

N is selected from the integer of 1-6,

Described mineral acid is selected from sulphuric acid, phosphoric acid, hydrochloric acid, hydrobromic acid, nitric acid, sulfurous acid, valeric acid, methanesulfonic acid, ethyl sulfonic acid, toluenesulfonic acid, salicylic acid, benzoic acid; Described organic acid is selected from formic acid, acetic acid, malonic acid, lactic acid, cinnamic acid, succinic acid, oxalic acid, citric acid, maleic acid, fumaric acid, malic acid, mandelic acid, tartaric acid, sulfonic acid.

Chemical compound shown in the preferred formula S-VIAa is shown in S-VIAa1

K is selected from the integer of 1-6,

R ₂Be selected from alkyl, replacement or the non-substituted benzyl of C1-6, the substituent group on the benzyl is selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-4 alkyl, C1-4 alkoxyl, C1-4 alkylamino, C1-4 alcoxyl C1-4 alkyl;

X is chloride ion, bromide ion or iodide ion.

Chemical compound shown in the preferred formula S-VIAa is shown in S-VIAa2

M is selected from the integer of 1-6,

X is chloride ion, bromide ion or iodide ion.

Chemical compound shown in the preferred formula S-VIAb is shown in S-VIAb1

N is selected from the integer of 1-6,

X is chloride ion, bromide ion or iodide ion.Chemical compound shown in the preferred formula S-VIAb is shown in S-VIAb2

M is selected from the integer of 1-6,

N is selected from the integer of 1-6,

X is chloride ion, bromide ion or iodide ion.

Chemical compound shown in the preferred formula S-VIB is shown in S-VIBa

K is selected from the integer of 1-6,

Chemical compound shown in the preferred formula S-VIB is shown in S-VIBb

Be selected from the integer of 1-6,

Chemical compound shown in the preferred formula S-VIBa is shown in S-VIBa1

K is selected from the integer of 1-6;

X is chloride ion, bromide ion or iodide ion.

Chemical compound shown in the preferred formula S-VIBa is shown in S-VIBa2

X is chloride ion, bromide ion or iodide ion.

Chemical compound shown in the preferred formula S-VIBb is shown in S-VIBb1

K is selected from the integer of 1-6,

N is selected from the integer of 1-6;

X is chloride ion, bromide ion or iodide ion.

Chemical compound shown in the preferred formula S-VIBb is shown in S-VIBb2

K is selected from the integer of 1-4,

M is selected from the integer of 1-4,

N is selected from the integer of 1-4;

X is chloride ion, bromide ion or iodide ion.

The quaternary ammonium salt (S-VI) of most preferred 1,7,9 substituted compounds is selected from following group: the preparation of following chemical compound is open in CN101139347A

No

Code name

R ¹

R ²

R ⁷

R ⁹

X

1

DH-214

H

(CH ₂) ₃C ₆H ₅

H

(CH ₂) ₃C ₆H ₅

Br

[0916]?

2

DH-272

H

CH ₂C ₆H ₅

H

(CH ₂) ₃C ₆H ₅

Br

3

DH-273

H

CH ₂C ₆H ₄(m-Cl)

H

(CH ₂) ₃C ₆H ₅

Br

4

DH-274

H

CH ₂C ₆H ₄(p-F)

H

(CH ₂) ₃C ₆H ₅

Br

5

DH-146

CH3

C ₂H ₅

OCH ₃

(CH ₂) ₃C ₆H ₅

I

6

DH-090

CH3

n-C ₄H ₉

OCH ₃

(CH ₂) ₃C ₆H ₅

I

7

DH-091

CH3

CH ₂C ₆H ₅

OCH ₃

(CH ₂) ₃C ₆H ₅

Br

8

DH-147

CH3

CH ₂C ₆H ₄(p-F)

OCH ₃

(CH ₂) ₃C ₆H ₅

Br

9

DH-148

CH3

(CH ₂) ₃C ₆H ₅

OCH ₃

(CH ₂) ₃C ₆H ₅

Br

22

H-2-54

CH3

CH ₂C ₆H ₅

OC ₄H ₉

(CH ₂) ₃C ₆H ₅

Br

23

H-2-81

CH3

CH ₂C ₆H ₅

OCH(CH ₂CH ₃) ₂

(CH ₂) ₃C ₆H ₅

Br

24

H-2-59

CH3

CH ₂C ₆H ₅

OC ₈H ₁₇

(CH ₂) ₃C ₆H ₅

Br

25

DH-280

CH3

CH ₂C ₆H ₅

OCH ₂C ₆H ₄(m-Cl)

(CH ₂) ₃C ₆H ₅

Br

26

DH-281

CH3

CH ₂C ₆H ₅

OCH ₂C ₆H ₄(p-F)

(CH ₂) ₃C ₆H ₅

Br

27

H-2-58

CH3

CH ₂C ₆H ₅

O(CH ₂) ₃C ₆H ₅

(CH ₂) ₃C ₆H ₅

Br

The preparation of following chemical compound is open in CN101429198A

No

Code name

R ¹

R ²

R ⁷

R ⁹

X

13

H-2-57

CH ₃

CH ₂C ₆H ₅

OCH ₂CH(CH ₃) ₂

C ₂H ₅

Br

14

H-2-56

CH ₃

CH ₂C ₆H ₅

OCH ₂C ₆H ₅

C ₂H ₅

Br

15

H-2-77

CH ₃

CH ₂C ₆H ₅

O(CH ₂) ₃C ₆H ₅

C ₂H ₅

Br

16

H-2-24

CH ₃

CH ₂C ₆H ₅

OCH ₂C ₆H ₅

n-C ₄H ₉

Br

17

H-2-53

CH ₃

CH ₂C ₆H ₅

OCH ₂CH(CH ₃) ₂

n-C ₄H ₉

Br

18

H-2-65

CH ₃

CH ₂C ₆H ₅

OC ₄H ₉

CH ₂CH(CH ₃) ₂

Br

19

H-2-69

CH ₃

CH ₂C ₆H ₅

OC ₁₀H ₂₁

CH ₂CH(CH ₃) ₂

Br

20

H-2-70

CH ₃

CH ₂C ₆H ₅

(CH ₂) ₃C ₆H ₅

CH ₂CH(CH ₃) ₂

Br

31

D-6

CH＝CHC ₆H ₄(p-OCH ₃)

CH ₂C ₆H ₅

H

n-C ₄H ₉

Br

32

D-8

CH＝CHC ₆H ₄(p-OCH ₃)

CH ₂C ₆H ₅

H

(CH ₂) ₃C ₆H ₅

Br

33

D-10

CH＝CHC ₆H ₄(p-OCH ₃)

CH ₂C ₆H ₅

OC ₄H ₉

(CH ₂) ₃C ₆H ₅

Br

34

D-18

CH＝CHC ₆H ₄(p-NO ₂)

CH ₂C ₆H ₅

OC ₄H ₉

(CH ₂) ₃C ₆H ₅

Br

[0919]?

1 replacement

7 replacements

R ⁹Be selected from hydrogen; replace or non-substituted C1-6 straight or branched alkyl; hydroxyl; replace or non-substituted C1-6 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-6 straight or branched alkylthio group; C1-6 alcoxyl C1-6 alkyl; aldehyde radical; replace or non-substituted C1-6 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-6 straight or branched alkyl-ester group; replace or non-substituted C1-6 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-6; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6;

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

Preferred R ⁹Be selected from H, CH ₃, n-C ₄H ₉, i-butyl, (CH ₂) ₃C ₆H ₅, (CH ₂) ₃C ₆H ₅Y,

Preferred m is selected from the arbitrary integer of 0-4;

Preferred n is selected from the arbitrary integer of 0-4;

Most preferred R ⁹Be selected from n-C ₄H ₉, i-butyl, CH ₂C ₆H ₅Y, (CH ₂) ₃C ₆H ₅,

Most preferred m=0,1,2

Most preferred n=0,1

The preparation of following chemical compound is open in CN102146080A

Numbering	Code name	R ⁹	m	n
					1	CZY-1-11	n-C ₄H ₉	0	1
2	CZY-1-13	n-C ₄H ₉	1	0
					3	CZY-1-12	n-C ₄H ₉	1	1
4	CZY-1-14	n-C ₄H ₉	2	1

[0937]?

5	CZY-1-15	i-butyl	0	1
					6	CZY-1-18	i-butyl	1	0
7	CZY-1-16	i-butyl	1	1
					8	CZY-1-17	i-butyl	2	1
9	CZY-1-5	CH ₂C ₆H ₅	0	1
					10	CZY-1-7	CH ₂C ₆H ₅	1	0
11	CZY-1-6	CH ₂C ₆H ₅	1	1
					12	CZY-1-21	CH ₂C ₆H ₅	2	1
13	CZY-1-8	CH ₂C ₆H ₄(p-F)	0	1
					14	CZY-1-10	CH ₂C ₆H ₄(p-F)	1	0
15	CZY-1-9	CH ₂C ₆H ₄(p-F)	1	1
					16	CZY-1-19	CH ₂C ₆H ₄(p-F)	2	1
17	CZY-1-24	CH ₂C ₆H ₄(m-Cl)	0	1
					18	CZY-1-25	CH ₂C ₆H ₄(m-Cl)	1	0
19	CZY-1-22	CH ₂C ₆H ₄(m-Cl)	1	1
					20	CZY-1-23	CH ₂C ₆H ₄(m-Cl)	2	1
21	CZY-1-1	(CH ₂) ₃C ₆H ₅	0	1
					22	CZY-1-4	(CH ₂) ₃C ₆H ₅	1	0
23	CZY-1-3	(CH ₂) ₃C ₆H ₅	1	1
					24	CZY-1-20	(CH ₂) ₃C ₆H ₅	2	1

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

Preferred R ⁹Be selected from H, replacement or non-substituted C1-6 straight or branched alkyl, (CH ₂) ₃C ₆H ₅,

(CH ₂) ₃C ₆H ₅Y；

Preferred m is selected from the arbitrary integer of 0-4;

Preferred n is selected from the arbitrary integer of 0-4;

Most preferred R ⁹Be selected from H, CH ₃, n-C ₄H ₉, (CH ₂) ₃C ₆H ₅, (CH ₂) ₃C ₆H ₅Y,

Most preferred m=0,1,2

Most preferred n=0,1

The preparation of following chemical compound is open in CN102146080A

Numbering	Code name	R ⁹	m	n
					25	CZY-3-45	H	1	0
26	CZY-3-47	H	1	1
					27	CZY-3-63	CH ₃	0	1
28	CZY-3-65	CH ₃	1	0
					29	CZY-3-64	CH ₃	1	1
30	CZY-3-66	CH ₃	2	1
					31	CZY-3-14	n-C ₄H ₉	0	1
32	CZY-3-15	n-C ₄H ₉	1	0
					33	CZY-3-13	n-C ₄H ₉	1	1
34	CZY-3-37	n-C ₄H ₉	2	1

[0951]?

35	CZY-3-7	CH ₂C ₆H ₅	0	1
					36	CZY-3-9	CH ₂C ₆H ₅	1	0
37	CZY-3-8	CH ₂C ₆H ₅	1	1
					38	CZY-3-36	CH ₂C ₆H ₅	2	1
39	CZY-3-19	CH ₂C ₆H ₄(p-F)	0	1
					40	CZY-3-21	CH ₂C ₆H ₄(p-F)	1	0
41	CZY-3-20	CH ₂C ₆H ₄(p-F)	1	1
					42	CZY-3-42	CH ₂C ₆H ₄(p-F)	2	1
43	CZY-3-52	CH ₂C ₆H ₄(m-Cl)	0	1
					44	CZY-3-53	CH ₂C ₆H ₄(m-Cl)	1	0
45	CZY-3-50	CH ₂C ₆H ₄(m-Cl)	1	1
					46	CZY-3-51	CH ₂C ₆H ₄(m-Cl)	2	1
47	CZY-3-5	(CH ₂) ₃C ₆H ₅	0	1
					48	CZY-3-4	(CH ₂) ₃C ₆H ₅	1	0
49	CZY-3-3	(CH ₂) ₃C ₆H ₅	1	1
					50	CZY-3-34	(CH ₂) ₃C ₆H ₅	2	1

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

(CH ₂) ₃C ₆H ₅Y；

Preferred m is selected from the arbitrary integer of 0-4;

Preferred n is selected from the arbitrary integer of 0-4;

Most preferred m=0,1,2

Most preferred n=0,1

The preparation of following chemical compound is open in CN102146080A

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

Preferred R ⁹Be selected from H, replacement or non-substituted C1-6 straight or branched alkyl, (CH ₂) ₃C ₆H ₅, (CH ₂) ₃C ₆H ₅Y;

Preferred m is selected from the arbitrary integer of 0-4;

Preferred n is selected from the arbitrary integer of 0-4;

Most preferred R ⁹Be selected from H, CH ₃, n-C ₄H ₉, (CH ₂) ₃C ₆H ₅

Most preferred m=0,1,2

Most preferred n=0,1

The preparation of following chemical compound is open in CN102146080A

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

Preferred m is selected from the arbitrary integer of 0-4;

Preferred n is selected from the arbitrary integer of 0-4;

Most preferred m=0,1,2

Most preferred n=0,1

The preparation of following chemical compound is open in CN102146080A

Numbering	Code name	R ⁹	m	n
					86	CZY-3-57	H	0	1
87	CZY-3-58	H	1	0
					88	CZY-3-48	H	1	1
89	CZY-3-49	H	2	1

Replace or non-substituted C1-6 straight or branched alkyl on substituent group be selected from: hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group;

Y independently is selected from hydroxyl, sulfydryl, amino, aldehyde radical, carboxyl, carbamoyl, halogen, nitro, cyano group, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkylamino, C1-6 alcoxyl C1-6 alkyl;

Preferred five member aromatic is selected from

Preferred hexa-atomic aryl is selected from

Preferably contain 1-4 and be selected from N, the heteroatomic quinary heterocyclic radical of O or S is selected from:

Preferably contain 1-4 and be selected from N, the heteroatomic hexa-member heterocycle base of O or S is selected from:

The applicant has found the antibacterial activity of Yageine derivates by systematic study, and namely Yageine derivates can be used for the anti-infective treatment.Described infection can be caused by gram negative bacteria, Gram-positive bacterium.Described antibacterial is selected from acinetobacter, Bacillus, campylobacter, chlamydia, the coating Pseudomonas, fusobacterium, the citric acid Pseudomonas, Escherichia, the intestinal Pseudomonas, Enterococcus, Francisella, haemophilus, Helicobacter, the white stone Bacillus of Cray, listeria, do not draw all and belong to, Mycobacterium, Neisser is Pseudomonas, proteus, Rhodopseudomonas, Salmonella, Serratia, Shigella, Stenotrophomonas belongs to, staphylococcus, chain shape Coccus or Nie Ersen Pseudomonas.Further described antibacterial is selected from staphylococcus aureus, staphylococcus epidermidis, enterococcus faecalis, enterococcus faecalis, escherichia coli, Klebsiella Pneumoniae, bacillus pyocyaneus, clostridium perfringen, motionless clostridium perfringen, moraxelle catarrhalis or escherichia coli.

The specific embodiment

Embodiment A-1

2-replaces the general synthesis technique (201-206) of beta-carboline alkaloid derivant:

B-carboline (2mmol), add an amount of ethyl acetate it is dissolved fully, add corresponding bromine/alkane iodide (10-20mmol), reflux 8 hours, be cooled to room temperature, the solid that filtration is separated out, the ethyl acetate washing is dissolved in solid in the dehydrated alcohol subsequently, reflux is to clarification, filtered while hot is placed the refrigerator recrystallization, gets white or pale yellow crystals.

2-benzyl-1-methyl-B-carboline bromine salt (201): take 1-methyl-B-carboline and cylite as raw material, get light yellow crystal (0.46g, 65%), mp〉270 ℃; FAB-MS m/e 273; IR (KBr) 3420,1750-3250,1634,1575,1525,1500,1452,1331,1299,1258,1229,1146,740; 1H-NMR (500MHz, DMSO-d6) δ 12.94 (1H, s, NH); (8.80-8.82 1H, d, J=7.0Hz, H-3); (8.73-8.75 1H, d, J=6.5Hz, H-4); (8.48-8.50 1H, d, J=7.5Hz, H-5); (7.79-7.80 2H, m, H-8, H-7); (7.25-7.47 6H, m, H-6, PhH); 6.06 (2H, s, NCH ₂Ph); 3.06 (3H, s, CH ₃).

2-benzyl-B-carboline bromine salt (202): take B-carboline and cylite as raw material, get light yellow crystal (0.52g, 77%), mp〉270 ℃; FAB-MS m/e 259; IR (KBr) 3395,1750-3250,1642,1520,1498,1337,1258,120,757,732; ¹H-NMR (500MHz, DMSO-d ₆) δ 12.86 (1H, s, NH); (9.62 1H, d, J=7.0Hz, H-1); (8.83-8.87 2H, m, H-3, H-4); (8.50-8.52 1H, d, J=5.5Hz, H-5); (7.79-7.84 2H, m, H-8, H-7); (7.43-7.56 6H, m, H-6, PhH); 6.00 (2H, s, NCH ₂Ph).

7-methoxyl group-2-benzyl-1-methyl-B-carboline bromine salt (203): take 7-methoxyl group-1-methyl-B-carboline and cylite as raw material, get light yellow crystal (0.64g, 84%), mp〉270 ℃; FAB-MS m/e 303; IR (KBr) 1750-3250,1632,1505,1457,1336,1286,1225,1022,830,803,733; ¹H-NMR (500MHz, DMSO-d ₆) δ 12.79 (1H, s, NH); (8.73-8.75 1H, d, J=6.5Hz, H-3); (8.57-8.59 1H, d, J=8.0Hz, H-4); (8.32-8.37 1H, m, H-5); (7.37-7.44 3H, m, H-8, H-6, PhH); (7.22-7.24 2H, m, PhH); (7.12-7.13 1H, m, PhH); (7.06-7.09 1H, m, PhH); 5.99 (2H, s, NCH ₂Ph).

3-ethoxy carbonyl-2-benzyl-1-methyl-B-carboline bromine salt (204): take 3-ethoxy carbonyl-1-methyl-B-carboline and cylite as raw material, get light yellow crystal (0.42g, 49%), mp〉270 ℃; FAB-MS m/e425; IR (KBr) 3421,2250-3250,1721,1627,1579,1514,1452,1367,1334,1261,1136,1105,1020,735; ¹H-NMR (500MHz, DMSO-d ₆) δ 13.37 (1H, s, NH); (9.26 1H, s, H-4); (8.61-8.63 1H, d, J=8.0Hz, H-8); (7.87-7.88 2H, m, H-5, H-7); (7.52-7.55 1H, m, H-6); (7.33-7.39 3H, m, PhH); (7.10-7.12 2H, m, PhH); 6.21 (2H, s, NCH ₂Ph); 4.33-4.38 (2H, m, CO ₂CH ₂CH ₃); 3.14 (3H, s, CH ₃); 1.20-1.22 (3H, m, CO ₂CH ₂CH ₃).

2-phenylpropyl-1-methyl-B-carboline bromine salt (205): take 1-methyl-B-carboline and 1-bromo-3-phenyl-propane as raw material, get light yellow crystal (0.58g, 76%), mp〉270 ℃; FAB-MS m/e 301; IR (KBr) 3250-3600,2250-3250,1634,1574,1522,1499,1453,1330,1229,821,754; ¹H-NMR (500MHz, DMSO-d ₆) δ 12.87 (1H, s, NH); (8.68-8.69 1H, d, J=6.5Hz, H-3); (8.64-8.65 1H, d, J=6.5Hz, H-5); (8.45-8.47 1H, d, J=8.0Hz, H-8); (7.76-7.81 2H, m, H-4, H-6); (7.42-7.46 2H, m, H-7); (7.17-7.31 5H, m, PhH); 4.71-4.75 (2H, m, NCH ₂CH ₂CH ₂Ph); 3.10 (3H, s, CH ₃); 2.75-2.78 (2H, m, NCH ₂CH ₂CH ₂Ph); 2.22-2.28 (2H, m, N CH ₂CH ₂CH ₂Ph).

2-phenylpropyl-B-carboline bromine salt (206): take B-carboline and 1-bromo-3-phenyl-propane as raw material, get light yellow crystal 0.61g, yield 83%, mp〉270 ℃; FAB-MS m/e 287; IR (KBr) 3499,3431,1750-3250,1643,1517,1496,1339,1260,1137,826,754; ¹H-NMR (500MHz, DMSO-d ₆) δ 12.85 (1H, s, NH); (9.51 1H, s, H-1); (8.82-8.83 1H, d, J=6.5Hz, H-3); (8.77-8.79 1H, d, J=6.5Hz, H-4); (8.50-8.51 1H, d, J=8.0Hz, H-5); (7.77-7.83 2H, m, H-8, H-6); (7.43-7.46 1H, m, H-7); (7.12-7.26 5H, m, PhH); 4.81-4.84 (2H, m, NCH ₂CH ₂CH ₂Ph); 2.67-2.70 (2H, m, NCH ₂CH ₂CH ₂Ph); 2.31-2.37 (2H, m, NCH ₂CH ₂CH ₂Ph).

2-normal-butyl-B-carboline iodine salt (207): take B-carboline and iodo-n-butane as raw material, get light yellow crystal 0.46g, yield 75%, mp〉270 ℃; FAB-MS m/e 225; IR (KBr) 3404,1750-3250,1643,1573,1518,1457,1334,1255,1148,1118,869; ¹H-NMR (500MHz, DMSO-d ₆) δ 12.86 (1H, s, NH); (9.52 1H, s, H-3); (8.85-8.86 1H, d, J=6.5Hz, H-1); (8.77-8.79 1H, d, J=6.5Hz, H-4); (8.51-8.53 1H, d, J=8.0Hz, H-5); (7.79-7.84 2H, m, H-8, H-7); (7.45-7.48 1H, m, H-6); 4.77-4.80 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.97-2.03 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.32-1.39 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.93-0.96 (2H, m, NCH ₂CH ₂CH ₂CH ₃).

Embodiment A-2

The general synthesis technique (208-215) of 7 alkylated reactions:

With 9-ethyl-1-methyl-B-carboline-7-alcohol (2.0mmol), DMF (30ml), 60% sodium hydride (0.2g, 5mmol) mix, stir 5min under room temperature or the ice bath, add subsequently corresponding halogenated alkane (3-5mmol), stirring reaction 0.5-2 hour, TLC tracking detection (developing solvent: acetone/petroleum ether=1:1), react complete, reactant mixture is poured into water, adds the 10M sodium hydroxide, the stirring at room reaction is spent the night, filter, massive laundering is dissolved in dehydrated alcohol with solid, transfers pH to 3-4 with concentrated hydrochloric acid, concentrating under reduced pressure, dehydrated alcohol band water number, acetone or acetone/diethyl ether recrystallization get white or light yellow solid.Solid is dissolved in the mixed solution of ethyl acetate/water, and with saturated solution of sodium bicarbonate alkalization, ethyl acetate extraction, washing, saturated salt washing, drying, activated carbon decolorizing filters, concentrating under reduced pressure, and ether or ether/petroleum ether mixed solution recrystallization gets white crystal.

7-ethyoxyl-9-ethyl-1-methyl-B-carboline (208): take iodoethane as raw material, get white crystal 0.38g, yield 76%, mp 117-118 ℃; FAB-MS m/e (M+1) 255; IR (KBr) 2978,2931,1620,1560,1446,1407,1342,1208,1139,1048,972,817; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.28 (1H, d, J=5.5Hz, H-3); (7.96-7.98 1H, d, J=8.5Hz, H-4); (7.74-7.75 1H, d, J=5.5Hz, H-5); (6.87-6.90 2H, m, H-6, H-8); 4.52-4.56 (2H, m, NCH ₂CH ₃); 4.16-4.20 (2H, m, OCH ₂CH ₃); 3.05 (3H, s, CH ₃); 1.43-1.51 (6H, m, NCH ₂CH ₃, OCH ₂CH ₃).

7-isopropoxy-9-ethyl-1-methyl-B-carboline (209): take the 2-N-Propyl Bromide as raw material, get white crystal 0.42g, yield 79%, mp 114-115 ℃; FAB-MS m/e (M+1) 269; IR (KBr) 2973,2926,1620,1565,1446,1373,1209,1108,1038,978,813; ¹H-NMR (500MHz, CDCl ₃) δ 8.25-8.27 (1H, d, J=5.5Hz, H-3); (7.94-7.95 1H, d, J=9.0Hz, H-4); (7.70-7.71 1H, d, J=5.0Hz, H-5); (6.85-6.87 2H, m, H-6, H-8); 4.68-4.73 (1H, m, OC _H[CH ₃] ₂); 4.49-4.54 (2H, m, NCH2CH ₃); (3.01 3H, s, CH3); 1.40-1.45 (9H, m, NCH2CH3, OCH[CH3] 2).

7-n-butoxy-9-ethyl-1-methyl-B-carboline (210): take iodo-n-butane as raw material, get white crystal 0.48g, yield 85%, mp 109-110 ℃; FAB-MS m/e (M+1) 283; IR (KBr) 2973,2938,2875,1623,1560,1453,1409,1343,1260,1215,1140,1047,1007,810; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=6.0Hz, H-3); (7.95-7.97 1H, d, J=8.5Hz, H-4); (7.73-7.74 1H, d, J=5.0Hz, H-5); (6.86-6.90 2H, m, H-6, H-8); 4.52-4.56 (2H, m, NCH ₂CH ₃); 4.09-4.11 (2H, m, NCH ₂CH ₃); 3.05 (3H, s, CH ₃); 1.82-1.87 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 1.54-1.58 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 1.43-1.46 (3H, m, NCH ₂CH ₃); 1.00-1.03 (3H, m, OCH2CH2CH ₂CH ₃).

7-decane oxygen base-9-ethyl-1-methyl-B-carboline (211): take 1-iodo decane as raw material, get white crystal 0.61g, yield 83%, mp 76-77 ℃; FAB-MS m/e (M+1) 367; IR (KBr) 3047,2923,2850,1628,1561,1443,1345,1296,1207,1147,1027,859,821,786; ¹H-NMR (500MHz, CDCl ₃) δ 8.28-8.29 (1H, d, J=5.0Hz, H-3); (7.97-7.99 1H, d, J=9.0Hz, H-4); (7.74-7.75 1H, d, J=4.5Hz, H-5); (6.88-6.91 2H, m, H-6, H-8); 4.54-4.59 (2H, m, NCH ₂CH ₃); 4.10-4.12 (2H, m, OCH ₂[CH ₂] ₈CH ₃); 3.05 (3H, s, CH ₃); 1.85-1.89 (3H, m, NCH ₂CH ₃), 1.30-1.56 (16H, m, OCH ₂[CH ₂] ₈CH ₃); 0.90-0.93 (3H, m, O[CH ₂] ₉CH ₃).

7-five fluorine benzyloxy-9-ethyl-1-methyl-B-carboline (212): be raw material with 2,3,4,5,6-, five fluorine cylites, get white crystal 0.64g, yield 78%, mp 205-206 ℃; FAB-MS m/e (M+1) 407; IR (KBr) 3063,2977,1620,1565,1507,1442,1408,1350,1208,1139,1060,938,815; ¹H-NMR (500MHz, CDCl ₃) δ 8.30-8.31 (1H, d, J=5.5Hz, H-3); (8.01-8.02 1H, d, J=8.5Hz, H-4); (7.55-7.65 1H, d, J=5.0Hz, H-5); (6.93-6.99 2H, m, H-6, H-8); 5.29 (2H, s, OCH ₂Ph); 4.55-4.59 (2H, m, NCH ₂CH ₃); 3.05 (3H, s, CH ₃); 1.45-1.48 (3H, m, NCH ₂CH ₃).

The general synthesis technique (213-215) of the B-carboline bromine salt derivative of 2 replacements:

7-replacement-9-ethyl-1-methyl-B-carboline (1mmol), ethyl acetate (30ml), corresponding halogenated alkane (10mmol) are mixed, reflux 5h, TLC follows the tracks of detection, the most of reaction of question response raw material is complete, stops to reflux, and reaction mixture is cooled off, filter, an amount of ethyl acetate washing, solid matter dehydrated alcohol recrystallization 1-2 time with obtaining gets light yellow graininess crystal.

7-ethyoxyl-2-benzyl-9-ethyl-1-methyl-B-carboline bromine salt (213): take 7-ethyoxyl-9-ethyl-1-methyl-B-carboline and cylite as raw material, get light yellow crystal 0.36g, yield 85%, mp 260-261 ℃; FAB-MS m/e 345; IR (KBr) 3401,2976,2874,1623,1451,1376,1341,1259,1223,1134,1041,826,735; ¹H-NMR (500MHz, DMSO-d ₆) δ 8.78-8.79 (1H, d, J=6.5Hz, H-3); (8.60-8.62 1H, d, J=6.5Hz, H-4); (8.37-8.39 1H, d, J 9.0Hz, H-5); (7.36-7.43 4H, m, H-6, H-8, PhH); (7.19-7.20 2H, d, J=7.0Hz, PhH); (7.08-7.10 1H, m, PhH); 6.04 (2H, s, NCH ₂Ph); 4.69-4.74 (2H, m, NCH ₂CH ₃); 4.26-4.30 (2H, m, OCH ₂CH ₃); 3.10 (3H, s, CH ₃); 1.37-1.45 (6H, m, NCH ₂CH ₃, OCH ₂CH ₃).

7-n-butoxy-2-benzyl-9-ethyl-1-methyl-B-carboline bromine salt (214): take 7-n-butoxy-9-ethyl-1-methyl-B-carboline and cylite as raw material, get light yellow crystal 0.39g, yield 86%, mp215-216 ℃; FAB-MS m/e 373; IR (KBr) 3386,3045,2958,2931,2869,1622,1577,1454,1374,1256,1221,1132,1032,809,735; ¹H-NMR (500MHz, DMSO-d ₆) δ 8.80-8.81 (1H, d, J=6.5Hz, H-3); (8.62-8.63 1H, d, J=6.5Hz, H-4); (8.37-8.39 1H, d, J=8.5Hz, H-5); (7.35-7.43 5H, m, H-6, H-8, PhH); (7.20-7.21 2H, d, J=7.0Hz, PhH); (7.08-7.10 1H, m, PhH); 6.06 (2H, s, NCH ₂Ph); 4.70-4.75 (2H, m, NCH ₂CH ₃); 4.21-4.24 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 3.11 (3H, s, CH ₃); 1.78-1.83 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 1.48-1.55 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 1.38-1.41 (3H, m, NCH ₂CH ₃); 0.97-1.00 (3H, m, OCH ₂CH ₂CH ₂CH ₃).

7-five fluorine benzyloxy-2-benzyl-9-ethyl-1-methyl-B-carboline bromine salt (215): take 7-five fluorine benzyloxy-9-ethyl-1-methyl-B-carboline and cylite as raw material, get light yellow crystal 0.50g, yield 87%, mp196-197 ℃; FAB-MS m/e 497; IR (KBr) 3411,2988,1624,1579,1504,1454,1217,1136,1057,973,942,828,732; ¹H-NMR (500MHz, DMSO-d ₆) δ 8.82-8.83 (1H, d, J=6.5Hz, H-3); (8.66-8.67 1H, d, J=6.5Hz, H-4); (8.43-8.45 1H, d, J=9.0Hz, H-5); (7.63 1H, m, H-6); (7.36-7.44 3H, m, H-8, PhH); (7.14-7.22 3H, m, PhH); 6.07 (2H, s, NCH ₂Ph); 5.48 (2H, s, OCH ₂Ph); 4.75-4.76 (2H, m, NCH ₂CH ₃); 3.13 (3H, s, CH ₃); 1.42-1.44 (3H, m, NCH ₂CH ₃).

Embodiment A-3

The general synthesis technique (216-223) of 7-alkoxyl-9-normal-butyl-1-methyl-beta-carboline derivatives:

With 9-normal-butyl-1-methyl-B-carboline-7 alcohol (2.0mmol), DMF (30ml), 60% sodium hydride (0.2g, 5mmol) mix, stir 5min under room temperature or the ice bath, add subsequently corresponding halogenated alkane (3.5-5mmol), stirring reaction 1-2 hour, TLC tracking detection (developing solvent: acetone/petroleum ether=1:1), react complete, reactant mixture is poured into water, adds the 10M sodium hydroxide, the stirring at room reaction is spent the night, filter, massive laundering is dissolved in dehydrated alcohol with solid, transfers pH to 3-4 with concentrated hydrochloric acid, concentrating under reduced pressure, dehydrated alcohol band water number, acetone or acetone/diethyl ether recrystallization get white or light yellow solid.Solid is dissolved in the mixed solution of ethyl acetate/water, and with sodium bicarbonate alkalization, ethyl acetate extraction, washing, saturated salt washing, drying, activated carbon decolorizing filters, concentrating under reduced pressure, and ether or ether/petroleum ether mixed solution recrystallization gets white crystal.

7-ethyoxyl-9-normal-butyl-1-methyl-B-carboline (216): take iodoethane as raw material, get white crystal 0.42g, yield 75%, mp 93-94 ℃; FAB-MS m/e (M+1) 283; IR (KBr) 3052,2961,2928,2869,1622,1562,1450,1410,1360,1255,1193,1139,1048,948,809; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=5.0Hz, H-3); (7.96-7.98 1H, d, J 8.5Hz, H-4); (7.75-7.77 1H, d, J=5.0Hz, H-5); (6.86-6.91 2H, m, H-6, H-8); 4.44-4.47 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 4.16-4.20 (2H, m, OCH ₂CH ₃); 3.05 (3H, s, CH ₃); 1.78-1.84 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.42-1.51 (5H, m, NCH ₂CH ₂CH ₂CH ₃, OCH ₂CH ₃); 0.97-1.00 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

7-isopropoxy-9-normal-butyl-1-methyl-B-carboline (217): take the 2-N-Propyl Bromide as raw material, get yellow oil 0.41g, yield 72%; FAB-MS m/e (M+1) 297; IR (KBr) 3422,2970,2930,1626,1267,1447,1409,1376,1243,1191,1135,1113,986,816; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=5.5Hz, H-3); (7.95-7.97 1H, d, J=9.0Hz, H-4); (7.73-7.74 1H, d, J=5.5Hz, H-5); (6.87-6.88 2H, m, H-6, H-8); 4.68-4.73 (1H, m, OCH[CH ₃] ₂); 4.43-4.46 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 3.04 (3H, s, CH ₃); 1.78-1.84 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.37-1.47 (8H, m, NCH ₂CH ₂CH ₂CH ₃, OCH[CH ₃] ₂); 0.97-1.00 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

7-n-butoxy-9-normal-butyl-1-methyl-B-carboline (218): take iodo-n-butane as raw material, get white crystal 0.52g, yield 84%, mp 67-68 ℃; FAB-MS m/e (M+1) 311; IR (KBr) 3054,2958,2871,1622,1563,1451,1410,1246,198,1141,1044,1004,802; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=5.5Hz, H-3); (7.96-7.98 1H, d, J=8.5Hz, H-4); (7.76-7.77 1H, d, J=5.0Hz, H-5); (6.86-6.91 2H, m, H-6, H-8); 4.44-4.47 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 4.09-4.12 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 3.06 (3H, s, CH ₃); 1.79-1.88 (4H, m, NCH ₂CH ₂CH ₂CH ₃, OCH ₂CH ₂CH ₂CH ₃); 1.52-1.60 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.41-1.47 (2H, m, OCH ₂CH ₂CH ₂CH ₃); 0.97-1.03 (6H, m, NCH ₂CH ₂CH ₂CH ₃, OCH ₂CH ₂CH ₂CH ₃).

7-isobutoxy-9-normal-butyl-1-methyl-B-carboline (219): take isobutyl bromide as raw material, get yellow oil 0.47g, yield 73%; FAB-MS m/e (M+1) 325; IR (KBr) 3412,2959,2873,2529,1620,1570,1462,1336,1242,1197,1140,1111,1035,980,954,822; ¹H-NMR (500MHz, CDCl ₃) δ 8.25-8.26 (1H, d, J=5.0Hz, H-3); (7.93-7.95 1H, d, J=9.0Hz, H-4); (7.70-7.71 1H, d, J=5.0Hz, H-5); (6.86-6.88 2H, m, H-6, H-8); 4.41-4.45 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 4.24-4.29 (1H, m, OCH[CH ₂CH ₃] ₂); 3.01 (3H, s, CH ₃); 1.73-1.82 (6H, m, NCH ₂CH ₂CH ₂CH ₃, OCH[CH ₂CH ₃] ₂); 1.42-1.47 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.97-1.03 (9H, m, NCH ₂CH ₂CH ₂CH ₃, OCH[CH ₂CH ₃] ₂).

7-normal octane oxygen base-9-normal-butyl-1-methyl-B-carboline (220): take 1-iodo octane as raw material, get white crystal 0.62g, yield 85%, mp 75-76 ℃; FAB-MS m/e (M+1) 367; IR (KBr) 2927,2855,1622,1563,1446,1410,1373,1244,1198,1140,1042,806; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=5.0Hz, H-3); (7.95-7.97 1H, d, J=8.5Hz, H-4); (7.74-7.75 1H, d, J=5.5Hz, H-5); (6.85-6.90 2H, m, H-6, H-8); 4.43-4.47 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 4.08-4.10 (2H, m, OCH ₂[CH ₂] ₆CH ₃); 3.05 (3H, s, CH ₃); 1.80-1.89 (4H, m, NCH ₂CH ₂CH ₂CH ₃, OCH ₂CH ₂[CH ₂] ₅CH ₃); 1.29-1.53 (12H, m, O[CH ₂] ₂[CH ₂] ₅CH ₃, NCH ₂CH ₂CH ₂CH ₃); 0.97-1.00 (3H, m, NCH ₂CH ₂CH ₂CH ₃); 0.88-0.91 (3H, m, O[CH ₂] ₇CH ₃).

7-decane oxygen base-9-normal-butyl-1-methyl-B-carboline (221): take 1-iodo decane as raw material, get white crystal 0.65g, yield 81%, mp 67-68 ℃; FAB-MS m/e (M+1) 395; IR (KBr) 3427,2925,2852,1620,1462,1338,1231,1194,1138,1039,820; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=5.0Hz, H-3); (7.97-7.98 1H, d, J=8.5Hz, H-4); (7.78-7.79 1H, d, J=5.5Hz, H-5); (6.86-6.92 2H, m, H-6, H-8); 4.45-4.48 (2H, m, OCH ₂[CH ₂] ₈CH ₃); 4.08-4.11 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 3.09 (3H, s, CH ₃); 1.78-1.89 (4H, m, OCH ₂CH ₂[CH ₂] ₇CH ₃, NCH ₂CH ₂CH ₂CH ₃); 1.25-1.55 (16H, m, O[CH ₂] ₂[CH ₂] ₇CH ₃, NCH ₂CH ₂CH ₂CH ₃); 0.97-1.00 (3H, m, NCH ₂CH ₂CH ₂CH ₃); 0.83-0.84 (3H, m, O[CH ₂] ₉CH ₃).

7-phenylpropyl alcohol alkoxyl-9-normal-butyl-1-methyl-B-carboline (222): take 1-bromo-2-phenyl-propane as raw material, get white crystal 0.56g, yield 75%, mp 89-90 ℃; FAB-MS m/e (M+1) 373; IR (KBr) 2954,2926,2869,1622,1561,1494,1445,1410,1366,1355,1244,1190,1139,1040,809,758; ¹H-NMR (500MHz, CDCl ₃) δ 8.26-8.27 (1H, d, J=5.5Hz, H-3); (7.94-7.96 1H, d, J=8.5Hz, H-4); (7.72-7.73 1H, d, J=5.5Hz, H-5); (7.21-7.31 5H, m, PhH); (6.83-6.89 2H, m, H-6, H-8); 4.41-4.44 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 4.09-4.11 (2H, m, OCH ₂CH ₂CH ₂Ph); 3.02 (3H, s, CH ₃); 2.86-2.89 (2H, m, OCH ₂CH ₂CH ₂Ph); 2.17-2.20 (OCH ₂CH ₂CH ₂Ph); 1.78-1.84 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.42-1.51 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.96-0.99 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

7-n-octyloxy-2-benzyl-9-normal-butyl-1-methyl-B-carboline bromine salt (223):

7-n-octyl-9-normal-butyl-1-methyl-B-carboline (1mmol), ethyl acetate (30ml), cylite (10mmol) are mixed, reflux 5 hours, TLC follows the tracks of detection, and the most of reaction of question response raw material is complete, stop to reflux, with the reaction mixture cooling, filter an amount of ethyl acetate washing, with solid matter dehydrated alcohol recrystallization three times that obtain, get light yellow graininess crystal 0.46g, yield 86%, mp196-198 ℃; FAB-MS m/e 457; IR (KBr) 2926,2857,1621,1560,1458,1374,1349,1247,1136,1034,819,727; ¹H-NMR (500MHz, DMSO-d ₆) δ 8.80-8.81 (1H, d, J=6.5Hz, H-3); (8.62-8.64 1H, d, J=6.5Hz, H-4); (8.37-8.40 1H, m, H-5); (7.35-7.43 4H, m, PhH); (7.19-7.20 2H, m, PhH, H-6); (7.08-7.10 1H, m, H-8); 6.05 (2H, s, NCH ₂Ph); 4.64-4.67 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 4.20-4.22 (2H, m, OCH ₂[CH ₂] ₆CH ₃); 3.09 (3H, s, CH ₃); 1.71-1.82 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.46-1.49 (2H, m, OCH ₂CH ₂[CH ₂] ₅CH ₃); 1.26-1.37 (12H, m, NCH ₂CH ₂CH ₂CH ₃, O[CH ₂] ₂[CH ₂] ₅CH ₃); 0.85-0.94 (6H, m, N[CH ₂] ₃CH ₃, O[CH ₂] ₇CH ₃).

Embodiment A-4

The general synthesis technique (224-225) of 7-alkoxyl-9-isobutyl group-1-methyl-beta-carboline derivatives:

With chemical compound 9-isobutyl group-1-methyl-B-carboline-7 alcohol (2.0mmol), DMF (30ml), 60% sodium hydride (0.2g, 5mmol) mix, stir 5min under room temperature or the ice bath, add subsequently corresponding halogenated alkane (3.5-5mmol), stirring reaction 1-2 hour, TLC tracking detection (developing solvent: acetone/petroleum ether=1:1), react complete, reactant mixture is poured into water, adds the 10M sodium hydroxide, the stirring at room reaction is spent the night, filter, massive laundering is dissolved in dehydrated alcohol with solid, transfers pH to 3-4 with concentrated hydrochloric acid, concentrating under reduced pressure, dehydrated alcohol band water number, acetone or acetone/diethyl ether recrystallization get white or light yellow solid.Solid is dissolved in the mixed solution of ethyl acetate/water, and with sodium bicarbonate alkalization, ethyl acetate extraction, washing, saturated salt washing, drying, activated carbon decolorizing filters, concentrating under reduced pressure, and ether or ether/petroleum ether mixed solution recrystallization gets white crystal.

7-isobutoxy-9-isobutyl group-1-methyl-B-carboline (224): take isobutyl bromide as raw material, get faint yellow oily thing 0.51g, yield 82%; FAB-MS m/e (M+1) 311; IR (KBr) 2956,2869,2480,1624,1575,1470,1432,1337,1256,1204,1138,1043,806; ¹H-NMR (500MHz, CDCl ₃) δ 8.27-8.28 (1H, d, J=5.0Hz, H-3); (7.97-7.98 1H, d, J=8.5Hz, H-4); (7.80-7.81 1H, d, J 5.5Hz, H-5); (6.86-6.92 2H, m, H-6, H-8); 4.28-4.30 (2H, m, OCH ₂CH[CH ₃] ₂); 3.85-3.86 (2H, m, NCH ₂CH[CH ₃] ₂); (3.08 3H, s, CH3); 2.13-2.29 (2H, m, NCH ₂CH[CH ₃] ₂, OCH ₂CH[CH ₃] ₂); 1.08-1.11 (6H, d, J=7.0Hz, OCH ₂CH[CH ₃] ₂); 0.94-0.95 (6H, d, J=6.5Hz, NCH ₂CH[CH ₃] ₂).

7-benzyloxy-9-isobutyl group-1-methyl-B-carboline (225): take cylite as raw material, get white crystal 0.59g, yield 86%, mp 110-112 ℃; FAB-MS m/e (M+1) 345; IR (KBr) 3432,2959,2928,2871,1618,1568,1448,1254,1196,1136,1004,813,731; ¹H-NMR (500MHz, CDCl ₃) δ 8.27-8.28 (1H, d, J=5.5Hz, H-3); (7.96-7.98 1H, d, J=8.5Hz, H-4); (7.74-7.75 1H, d, J=5.5Hz, H-5); (7.25-7.49 5H, m, PhH); (6.95-6.97 1H, m, H-6); (6.92-6.95 1H, m, H-8); 5.20 (2H, s, OCH ₂Ph); 4.23-4.24 (2H, d, J=7.0Hz, NCH ₂CH[CH ₃] ₂); 3.01 (3H, s, CH ₃); 2.18-2.21 (1H, m, NCH ₂CH[CH ₃] ₂), 0.87-0.89 (6H, d, J=6.5Hz, NCH ₂CH[CH ₃] ₂).

The general synthesis technique (226-227) of 7-alkoxyl-9-isobutyl group-1-methyl-B-carboline bromine salt:

7-alkoxyl-9-isobutyl group-1-methyl-B-carboline (1mmol), ethyl acetate (30ml), cylite (10mmol) are mixed, reflux, TLC follows the tracks of detection, the most of reaction of question response raw material is complete, stops to reflux, and reaction mixture is cooled off, filter, an amount of ethyl acetate washing, solid dehydrated alcohol recrystallization three times with obtaining get light yellow graininess crystal.

7-isobutoxy-2-benzyl-9-isobutyl group-1-methyl-B-carboline bromine salt (226): take 7-isobutoxy-9-isobutyl group-1-methyl-B-carboline as raw material, get light yellow crystal 0.38g, yield 79%, mp 255-257 ℃; FAB-MS m/e 401; IR (KBr) 3422,2992,2959,2894,1619,1578,1454,1376,1252,1212,1135,1003,825; ¹H-NMR (500MHz, DMSO-d ₆) δ 8.81-8.12 (1H, d, J=6.5Hz, H-3); (8.64-8.66 1H, d, J=6.5Hz, H-4); (8.38-8.40 1H, d, J=9.0Hz, H-5); (7.37-7.44 4H, m, PhH); (7.18-7.19 2H, d, J=7.0Hz, H-6, H-8); (7.09-7.11 1H, m, PhH); 6.05 (2H, s, CH ₂Ph); 4.53-4.55 (2H, d, J=7.5Hz, NCH ₂CH[CH ₃] ₂); 3.99-4.00 (2H, m, OCH ₂CH[CH ₃] ₂); 3.06 (3H, s, CH ₃); 1.98-2.14 (2H, m, NCH ₂CH[CH ₃] ₂, OCH ₂CH[CH ₃] ₂); 1.05-1.06 (6H, d, J=6.5Hz, NCH ₂CH[CH ₃] ₂); 0.83-0.84 (6H, d, J=7.0Hz, OCH ₂CH[CH ₃] ₂).

7-benzyloxy-2-benzyl-9-isobutyl group-1-methyl-B-carboline bromine salt (227): take 7-benzyloxy-9-isobutyl group-1-methyl-B-carboline as raw material, get light yellow crystal 0.43g, yield 84%, mp 218-220 ℃; FAB-MS m/e 435; IR (KBr) 3408,2959,2921,1622,1581,1454,1351,1253,1222,1137,1029,817,743; ¹H-NMR (500MHz, DMSO-d ₆) δ 8.80-8.81 (1H, d, J=6.5Hz, H-3); (8.64-8.65 1H, d, J=6.5Hz, H-4); (8.40-8.41 1H, d, J=8.5Hz, H-5); (7.34-7.54 9H, m, PhH); (7.17-7.19 3H, m, PhH, H-6, H-8); 6.04 (2H, s, NCH ₂Ph); 5.35 (2H, s, OCH ₂Ph); 4.51-4.52 (2H, d, J=7.5Hz, NCH ₂CH[CH ₃] ₂); 3.06 (3H, s, CH ₃); 2.02-2.05 (1H, m, NCH ₂CH[CH ₃] ₂); 0.79-0.80 (6H, d, J=6.5Hz, NCH ₂CH[CH ₃] ₂).

Embodiment A-5

The general synthesis technique (228-230) of the beta-carboline derivatives that 9-position branched alkyl replaces:

With B-carboline (10mmol), DMF (50ml), 60% sodium hydride (0.6g, 15mmol) mix, stir 5min under room temperature or the ice bath, add subsequently corresponding halogenated alkane (50mmol), stirring reaction 5-10h, TLC tracking detection (developing solvent: acetone/petroleum ether=1:1), react complete, reactant mixture is poured into water, adds the 10M sodium hydroxide, the stirring at room reaction is spent the night, filter, massive laundering is dissolved in dehydrated alcohol with solid, transfers pH to 3-4 with concentrated hydrochloric acid, concentrating under reduced pressure, dehydrated alcohol band water number, acetone or acetone/diethyl ether recrystallization get white or light yellow solid.Solid is dissolved in the mixed solution of ethyl acetate/water, and with sodium bicarbonate alkalization, ethyl acetate extraction, washing, saturated salt washing, drying, activated carbon decolorizing filters, concentrating under reduced pressure, and ether or ether/petroleum ether mixed solution recrystallization gets white needle-like crystals.

9-isopropyl-B-carboline (228): take B-carboline and 2-N-Propyl Bromide as raw material, get yellow oil 1.5g, yield 70%; FAB-MS m/e (M+1) 211; IR (KBr) 3042,2977,2419,2006,1631,1501,1459,1337,1244,1146,870,751; ¹H-NMR (500MHz, CDCl ₃) δ 9.04 (1H, s, H-3); (8.43-8.44 1H, d, J=5.0Hz, H-1); (8.15-8.17 1H, d, J=8.5Hz, H-4); (7.99-8.01 1H, d, J=4.5Hz, H-5); (7.56-7.61 2H, m, H-6, H-7); (7.26-7.30 1H, m, H-8); 5.02-5.08 (1H, m, NCH[CH ₃] ₂); 1.74-1.75 (6H, m, NCH[CH ₃] ₂).

9-isopropyl-1-methyl-B-carboline (229): take 1-methyl-B-carboline and 2-N-Propyl Bromide as raw material, get white crystal 1.64g, yield 73%, mp 155-156 ℃; FAB-MS m/e (M+1) 225; IR (KBr) 2976,1615,1554,1448,1399,1331,1306,1227,1163,1132,830,752; ¹H-NMR (500MHz, CDCl ₃) δ 8.30-8.31 (1H, d, J=5.0Hz, H-3); (8.11-8.12 1H, d, J=8.0Hz, H-5); (7.81-7.82 1H, d, J=5.0Hz, H-8); (7.69-7.70 1H, d, J=8.5Hz, H-4); (7.49-7.52 1H, m, H-6); (7.23-7.26 1H, m, H-7); 5.51-5.57 (1H, m, NCH[CH ₃] ₂); 3.12 (3H, s, CH ₃); 1.73-1.74 (6H, d, J=7.0Hz, NCH[CH ₃] ₂).

7-methoxyl group-9-isobutyl group-1-methyl-B-carboline (230): take 7-methoxyl group-1-methyl-B-carboline and isobutyl bromide as raw material, get white crystal 2.2g, yield 82%, mp 112-113 ℃; FAB-MS m/e (M+1) 269; IR (KBr) 2961,1621,1564,1496,1446,1403,1338,1254,1207,1139,1044,966,815; ¹H-NMR (500MHz, CDCl ₃) δ 8.29 (1H, s, H-3); (7.95-7.96 1H, d, J=8.5Hz, H-4); (7.73-7.74 1H, d, J=5.0Hz, H-5); (6.85-6.88 2H, m, H-6, H-8); 4.26-4.27 (2H, d, J=7.5Hz, NCH ₂CH[CH ₃] ₂); 3.93 (3H, s, OCH ₃); 3.01 (3H, s, CH ₃); 2.23-2.28 (1H, m, NCH ₂CH[CH ₃] ₂); 0.92-0.93 (6H, d, J=5.5Hz, NCH ₂CH[CH ₃] ₂).

Embodiment A-6

Synthesizing of 2-benzyl-9-normal-butyl-B-carboline bromine salt (231)

With 9-normal-butyl-B-carboline (2.24g, 10mmol), ethyl acetate (100ml) and cylite (50mmol) mix, heating reflux reaction 2h, the cooling reactant liquor filters to room temperature, ethyl acetate is fully washed, get faint yellow solid, dehydrated alcohol recrystallization three times gets pale yellow crystals 3.4g, yield 85%, mp 225-227 ℃; FAB-MS m/e 315; IR (KBr) 3444,2949,1641,1511,1457,1337,1216,1147,1070,755,721; ¹H-NMR (500MHz, DMSO-d ₆) δ 10.05 (1H, s, H-1), 8.85-8.88 (2H, m, H-3, H-4); (8.53-8.54 1H, d, J=8.0Hz, H-5); (7.95-7.97 1H, d, J=9.0Hz, H-6); (7.86-7.89 1H, m, H-7); (7.39-7.61 6H, m, H-8, PhH); 6.01 (2H, s, NCH ₂Ph); 4.64-4.67 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.83-1.86 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.30-1.35 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.88-0.91 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

Embodiment A-7

Synthesizing of 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-1-methyl B-carboline (232)

With 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-B-carboline (1.67g, 5mmol), DMF (100ml) mixes, stirring at room adds 60%NaH (0.6g to clarification, 15mmol), be stirred to without bubble and produce dropping alkyl halide (15mmol), stirring at room reaction 1-5h.Reactant mixture is poured in the frozen water into ethyl acetate extraction, combining extraction liquid, washing, the saturated salt washing adds ethanol 100ml, and concentrated hydrochloric acid is regulated pH to 2～3, is evaporated to dried, dehydrated alcohol band water number gets yellow oil, and acetone recrystallization is separated out yellow crystals.Filter, acetone is washed, the ether washing.Solid is soluble in water, sodium bicarbonate alkalization, ethyl acetate extraction, washing, anhydrous sodium sulfate drying, activated carbon decolorizing filters, concentrating under reduced pressure, residue is with ether or ether/petroleum ether recrystallization (1.4g, 80%), mp 147-148 ℃; FAB-MS m/e (M+1) 349; IR (KBr) 3005,2938,2836,1618,1581,1502,1460,1401,1353,1229,1123,1006,840,752; ¹H-NMR (500MHz, CDCl ₃) δ 8.50-8.51 (1H, d, J=5.5Hz, H-3); (8.18-8.19 1H, d, J=7.0Hz, H-8); (7.98-7.99 1H, d, J=5.0Hz, H-5); (7.61-7.64 1H, m, H-7); (7.43-7.45 1H, d, J=8.0Hz, H-6); (7.31-7.34 1H, m, H-4); (6.86 2H, s, PhH); 3.91-3.93 (9H, m, OCH ₃); 3.55 (3H, s, NCH ₃).

Embodiment A-8

Ethyl 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-methyl-B-carboline-3-carboxylate (233):

With 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-B-carboline-3-carboxylic acid, ethyl ester (4.1g, 10mmol) mix with DMF (200ml), stirring at room adds 60%NaH (1.2g to clarification, 30mmol), be stirred to without bubble and produce dropping alkyl halide (30mmol), stirring at room reaction 1-5h.Reactant mixture is poured in the frozen water into ethyl acetate extraction, combining extraction liquid, washing, the saturated salt washing adds ethanol 100ml, concentrated hydrochloric acid is regulated pH to 2～3, be evaporated to dried, dehydrated alcohol band water number, get yellow oil, acetone recrystallization is separated out yellow crystals, filters, acetone is washed, the ether washing.Solid is soluble in water, the sodium bicarbonate alkalization, ethyl acetate extraction, washing, anhydrous sodium sulfate drying, activated carbon decolorizing filters, and concentrating under reduced pressure, residue ether recrystallization gets white solid (3.0g, 71%), mp 173-175 ℃; FAB-MS m/e (M+1) 421; IR (KBr) 2939,2834,1702,1622,1583,1504,1461,1369,1319,1259,1128,1005,736; ¹H-NMR (500MHz, CDCl ₃) δ 8.87 (1H, s, H-4); (8.24-8.26 1H, d, J=7.5Hz, H-8); (7.64-7.67 1H, m, H-5); (7.47-7.48 1H, d, J=8.5Hz, H-6); (7.37-7.40 1H, m, H-7); (6.86 2H, s, PhH); 4.50-4.54 (2H, m, OCH ₂CH ₃); (3.90-3.92 9H, m, OCH3); 3.55 (3H, s, NCH ₃); 1.46-1.49 (3H, m, OCH ₂CH ₃).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-methyl-B-carboline-3-carboxylic acid (234):

Ethyl 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-methyl-B-carboline-3-carboxylate (5mmol), ethanol (100ml), sodium hydroxide (2.0g, 50mmol), water (200ml) mixes stirring at room reaction 24h, frozen water cooling, concentrated hydrochloric acid is transferred pH to 5 ~ 6, and decompression steams ethanol, separates out yellow solid, filter, washing, drying gets yellow solid (1.9g, 97%), mp 246-248 ℃; FAB-MS m/e (M+1) 393; IR (KBr) 3192,2944,2826,1747,1619,1585,1501,1466,1421,1362,1239,1126,1004,751; ¹H-NMR (500MHz, CDCl ₃) δ 8.93 (1H, s, H-4); (8.46-8.47 1H, d, J=7.5Hz, H-8); (7.66-7.71 2H, m, H-5, H-6); (7.37-7.40 1H, m, H-7); (6.94 2H, s, PhH); 3.78-3.84 (9H, m, OCH ₃); 3.56 (3H, s, NCH ₃).

N-ethoxy-9-methyl isophthalic acid-(3 ', 4 ', 5 '-trimethoxy) phenyl-B-carboline-3-Methanamide (235):

Chemical compound 82-85 (10mmol), dehydrated alcohol (150ml), 60% sodium hydride (15mmol), oxyethylamine (10ml), the about 1.5h of reflux is in the mixed liquor with reactant liquor impouring frozen water and ethyl acetate, rapidly layering, the water layer ethyl acetate extraction merges organic facies, washing, saturated nacl aqueous solution is washed, anhydrous sodium sulfate drying is crossed silica gel, concentrating under reduced pressure, ethyl acetate or recrystallization from ethyl acetate/petroleum ether get white crystal.Get white crystal 3.2g, yield 74%, mp 206-207 ℃; FAB-MS m/e (M+1) 436; IR (KBr) 3387,2935,2835,1658,1583,1538,1500,1457,1363,1320,1232,1125,1053,1004,842,742; ¹H-NMR (500MHz, CDCl ₃) δ 8.98 (1H, s, H-4); (8.26-8.27 1H, d, J=6.5Hz, H-8); (7.65-7.68 1H, m, H-5); (7.46-7.48 1H, d, J=8.5Hz, H-6); (7.37-7.40 1H, m, H-7); (6.83 2H, s, PhH); 3.92-3.97 (9H, m, OCH ₃); 3.88-3.90 (2H, m, NHCH ₂CH ₂OH); 3.68-3.70 (2H, m, NHCH ₂CH ₂OH); 3.55 (3H, s, NCH ₃).

Embodiment A-9

Synthesizing of 9-(4-luorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (236)

DMF (150ml), 4-fluorobenzyl chloride (4ml), KI (8.3g, 50mmol) mix, stirring at room reaction 1h adds 60%NaH (1.2g, 30mmol) and B-carboline-3-carboxylic acid, ethyl ester (4.8g, 20mmol), stirring at room reaction 10min, about 30 minutes of 60 ℃ of heating in water bath for reaction, TLC follows the tracks of detection, react complete, reactant mixture is poured in the cold water into ethyl acetate extraction, merge organic facies, washing adds 150ml ethanol, and concentrated hydrochloric acid is acidified to pH 2～3, be evaporated to dried, dehydrated alcohol band water, acetone recrystallization is separated out yellow solid.Filter, ether is washed, and gets yellow solid.In the water-soluble and ethyl acetate mixed liquor of solid, ethyl acetate layer is told in the sodium bicarbonate alkalization, the water layer ethyl acetate extraction, and the combined ethyl acetate phase, washing, saturated salt is washed, anhydrous sodium sulfate drying, activated carbon decolorizing.Filter, concentrating under reduced pressure, the ether recrystallization gets white crystal 6.0g, yield 84%, mp 132-133 ℃; FAB-MS m/e (M+1) 349; IR (KBr) 3059,3027,2986,2954,2904,1726,1622,1505,1371,1333,1303,1245,1107,1026,815,746; ¹H-NMR (500MHz, CDCl ₃) δ 8.90-8.91 (1H, d, J=4.5Hz, H-1); (8.23-8.25 1H, d, J=8.0Hz, H-4); (7.60-7.61 1H, t, H-5); (7.46-7.48 1H, d, J=8.0Hz, H-6); (7.38-7.40 1H, t, H-8); (7.26 1H, s, H-7); (6.95-7.14 4H, m, PhH); 5.59 (2H, s, NCH ₂Ph); 4.51-4.55 (2H, m, COOCH ₂CH ₃); 1.47-1.50 (3H, t, COOCH ₂CH ₃).

Synthesizing of N-ethoxy-9-(4-luorobenzyl)-B-carboline-3-Methanamide (237)

9-(4-luorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (1.74g, 5mmol), dehydrated alcohol (60ml), 60% sodium hydride (0.6g, 15mmol) mix, the about 1h of reflux, and TLC follows the tracks of detection.Reaction is finished, and with in the rapid impouring frozen water of reactant mixture/ethyl acetate mixed liquor, tells ethyl acetate layer under stirring, the water layer ethyl acetate extraction, combined ethyl acetate phase, washing, saturated salt washing, anhydrous sodium sulfate drying, activated carbon decolorizing filters, be evaporated to dried, separate out white solid, re-crystallizing in ethyl acetate gets white crystal (1.47g, 81%), mp 188-189 ℃; FAB-MS m/e (M+1) 364; IR (KBr) 3378,3066,2951,2917,2867,1647,1626,1590,1534,1497,1466,1423,1331,1217,1075,825,746; ¹H-NMR (500MHz, CDCl ₃) δ 8.98 (1H, s, H-1); (8.66 1H, s, NH); (8.23-8.24 1H, d, J=8.0Hz, H-4); (7.59-7.62 1H, t, H-5); (7.44-7.46 1H, d, J=8.5Hz, H-6); (7.35-7.38 1H, t, H-8); (7.25 1H, s, H-7); (6.95-7.12 4H, m, PhH); 5.57 (2H, s, NCH ₂Ph); 3.87-3.89 (2H, t, CH ₂CH ₂OH); 3.68-3.71 (2H, m, CH ₂CH ₂OH).

Embodiment A-10

3-methylol-9-methyl-B-carboline (238):

9-methyl-B-carboline-3-carboxylic acid, ethyl ester (10mmol), THF (200ml), LiBH ₄(30mmol) after the mixing, the about 12h of stirring at room reaction, TLC (petroleum ether/acetone=1/1) follows the tracks of detection, react complete, reaction mixture is slowly poured in the 200ml frozen water into stirring reaction 10min, drip concentrated hydrochloric acid to pH2-3, stirring at room 4h, mixture water cooling on the rocks, sodium hydroxide solution is regulated pH value to 9, ethyl acetate extraction, washing, saturated common salt washing, anhydrous sodium sulfate drying, decolorizing with activated carbon, filter (silica gel), be concentrated into dried, acetone solution, the refrigerator recrystallization, get white needle-like crystals (1.6g, 75%), mp139-140 ℃; FAB-MSm/e (M+1) 213; IR (KBr) 3172,2936,2836,1625,1553,1503,1473,1366,1334,1259,1131,1040,1018,972,882,746; ¹H-NMR (500MHz, CDCl ₃) δ 8.76 (1H, s, H-1); (8.09-8.13 1H, m, H-4); (7.93 1H, s, H-6); (7.59-7.63 1H, m, H-5); (7.43-7.45 1H, d, J=10.5Hz, H-8); (7.26-7.30 1H, m, H-7); 4.94 (2H, s, CH ₂OH); 3.91 (3H, s, NCH ₃).

3-aldehyde radical-9-methyl-B-carboline (239):

3-methylol-9-methyl-B-carboline (10mmol), acetonitrile (250ml), active MnO ₂(100mmol) mix, the about 2h of reflux, TLC follows the tracks of detection.React complete, remove by filter immediately MnO ₂, be evaporated to driedly, get yellow solid.Solid is dissolved in ethyl acetate, and activated carbon decolorizing is crossed silica gel, concentrating under reduced pressure, and acetone recrystallization gets white crystal (1.5g, 71%), mp180-181 ℃; FAB-MS m/e (M+1) 211; IR (KBr) 3358,3053,3023,2937,2816,2718,1689,1625,1579,1508,1473,1369,1335,1262,1175,1130,1061,1014,833,730; ¹H-NMR (500MHz, CDCl ₃) δ 10.24 (1H, s, CHO); (8.98 1H, s, H-1); (8.72 1H, s, H-4); (8.20-8.22 1H, d, J=10.0Hz, H-6); (7.38-7.70 3H, m, H-5, H-7, H-8); 4.03 (3H, s, CH ₃).

9-methyl-B-carboline-3-aldehyde radical thiosemicarbazones (240):

3-aldehyde radical-9-methyl-B-carboline (2mmol), thiosemicarbazides (2mmol), dehydrated alcohol (100ml) mix reflux 12 hours, the faint yellow solid of separating out in the course of reaction.Be cooled to room temperature, filter, get yellow solid.Dehydrated alcohol recrystallization three times gets yellow solid (0.37g, 65%), mp 234-235 ℃; FAB-MS m/e (M+1) 284; IR (KBr) 3369,3268,3169,2929,2694,1614,1500,1458,1408,1366,1331,1293,1249,1041,860,736; ¹H-NMR (500MHz, DMSO-d ₆) δ 14.28 (1H, s, NH); (9.24 1H, s, NH); (8.56 1H, s, H-1); (8.39 1H, s, H-4); (8.29-8.31 1H, d, J=10Hz, H-8); (8.04 1H, s, CH=NNH); (7.65-7.78 2H, m, H-5, H-7); (7.47 1H, s, CH=N); (7.37-7.40 1H, m, H-6); 4.05 (3H, s, NCH ₃).

An embodiment A-11 (this synthetic route has been carried out some deletions)! ! !

The general synthesis technique of 3-methylol-9-alkyl-1-methyl-B-carboline (241-242):

9-replacement-1-methyl-B-carboline-3-carboxylic acid, ethyl ester (10mmol), THF (200ml), LiBH4(30mmol) after the mixing, the about 10h of stirring at room reaction, TLC (petroleum ether/acetone=1/1) follows the tracks of detection, reacts complete, reaction mixture is slowly poured in the 200ml frozen water, stirring reaction 10min drips concentrated hydrochloric acid to pH2-3, stirring at room 10h, mixture water cooling on the rocks, sodium hydroxide solution is regulated pH value to 9, ethyl acetate extraction, washing, the saturated common salt washing, anhydrous sodium sulfate drying, decolorizing with activated carbon filters in (silica gel), be concentrated into dried, acetone solution, the refrigerator recrystallization gets white needle-like crystals.

3-methylol-1,9-dimethyl-B-carboline (241): with ethyl 1,9-dimethyl-B-carboline-3-carboxylate is raw material, gets white crystal 1.6g, yield 71%, mp175-176 ℃; FAB-MS m/e (M+1) 227; IR (KBr) 3157,2952,2860,1621,1559,1466,1356,1337,1287,1247,1105,1031,963,866,747; ¹H-NMR (500MHz, CDCl ₃) δ 8.07-8.09 (1H, m, H-4); (7.75 1H, s, H-6); (7.57-7.61 1H, m, H-5); (7.41-7.43 1H, d, J=10.5Hz, H-8); (7.24-7.28 1H, m, H-7); 4.87 (2H, s, CH ₂OH); 4.10 (3H, s, NCH ₃); 3.07 (3H, s, CH ₃).

3-methylol-9-ethyl-1-methyl-B-carboline (242): take ethyl 9-ethyl-1-methyl-B-carboline-3-carboxylate as raw material, get white crystal 1.5g, yield 63%, mp129-130 ℃; FAB-MS m/e (M+1) 241; IR (KBr) 3156,2978,2927,2860,1620,1559,1474,1342,1297,1231,113,1085,1036,888,743; ¹H-NMR (500MHz, CDCl ₃) δ 8.09-8.11 (1H, m, H-4); (7.79 1H, s, H-6); (7.57-7.62 1H, m, H-5); (7.45-7.47 1H, d, J=10.0Hz, H-8); (7.26-7.29 1H, m, H-7); 4.89 (2H, s, CH ₂OH); 4.57-4.62 (2H, m, NCH ₂CH ₃); 3.07 (3H, s, CH ₃); 1.43-1.46 (3H, m, NCH ₂CH ₃).

The general synthesis technique of 3-aldehyde radical-9-alkyl-1-methyl-B-carboline (243-244):

3-methylol-9-alkyl-1-methyl-B-carboline (10mmol), acetonitrile (250ml), active MnO ₂(100mmol) mix, the about 1h of reflux, TLC follows the tracks of detection.React complete, remove by filter immediately MnO ₂, be evaporated to driedly, get yellow solid.Solid is dissolved in ethyl acetate, and activated carbon decolorizing is crossed silica gel, concentrating under reduced pressure, and acetone recrystallization gets white crystal.

3-aldehyde radical-1,9-dimethyl-B-carboline (243): with 3-methylol-1,9-dimethyl-B-carboline is raw material, gets white crystal 1.4g, yield 63%, mp179-181 ℃; FAB-MS m/e (M+1) 225; IR (KBr) 3354,3056,2959,2811,1687,1616,1563,1496,1369,1330,1282,1246,1188,1132,1100,882,733; ¹H-NMR (500MHz, CDCl ₃) δ 10.35 (1H, s, CHO); (8.62 1H, s, H-4); (8.19-8.21 1H, d, J=10.0Hz, H-6); (7.68-7.72 1H, m, H-5); (7.53-7.55 1H, d, J=10.5Hz, H-7); (7.39-7.43 1H, m, H-8); 4.24 (3H, s, NCH ₃); 3.26 (3H, s, CH ₃).

3-aldehyde radical-9-ethyl-1-methyl-B-carboline (244): take 3-methylol-9-ethyl-1-methyl-B-carboline as raw material, get white crystal 1.6g, yield 67%, mp149-151 ℃; FAB-MS m/e (M+1) 239; IR (KBr) 3335,3067,2974,2931,2867,1676,1618,1569,1481,1446,1375,1339,1298,1230,1189,909,730; ¹H-NMR (500MHz, CDCl ₃) δ 10.34 (1H, s, CHO); (8.64 1H, s, H-4); (8.20-8.22 1H, d, J=10.0Hz, H-6); (7.39-7.69 3H, m, H-5, H-7, H-8); 4.68-4.73 (2H, m, NCH ₂CH ₃); 3.23 (3H, s, CH ₃); 1.52-1.55 (3H, m, NCH ₂CH ₃).

The general synthesis technique of 9-alkyl-1-methyl-B-carboline-3-aldehyde radical thiosemicarbazones (245-246):

3-aldehyde radical-9-alkyl-1-methyl-B-carboline 130-136 (5mmol), thiosemicarbazides (5mmol), dehydrated alcohol (100ml) mix reflux 12 hours, the faint yellow solid of separating out in the course of reaction.Be cooled to room temperature, filter, get yellow solid.The dehydrated alcohol recrystallization gets yellow solid.

1,9-dimethyl-B-carboline-3-aldehyde radical thiosemicarbazones (245):

With 3-aldehyde radical-1,9-dimethyl-B-carboline is raw material, gets yellow solid (0.38g, 64%), mp229-230 ℃; FAB-MS m/e (M+1) 298; IR (KBr) 3450,3414,3380,3281,3182,3108,2942,1619,1587,1493,1454,1356,1333,1285,1103,1048,855,742; ¹H-NMR (500MHz, DMSO-d ₆) δ 14.69 (1H, s, NH); (8.40 1H, s, NH); (8.33 1H, s, H-4); (8.24-8.26 1H, d, J=9Hz, H-8); (7.97 1H, s, CH=NNH); (7.77-7.79 1H, m, H-5); (7.66-7.72 1H, s, H-7); 7.35-7.37 (2H, m,, CH=N, H-6); 4.21 (3H, s, NCH ₃); 3.14 (3H, s, CH ₃).

9-ethyl-1-methyl-B-carboline-3-aldehyde radical thiosemicarbazones (246):

Take 3-aldehyde radical-9-ethyl-1-methyl-B-carboline as raw material, get yellow solid and get yellow solid (0.41g, 65%), mp 222-223 ℃; FAB-MS m/e (M+1) 312; IR (KBr) 3383,3261,3131,2972,2929,1615,1546,1491,1451,1344,1297,1228,1050,858,747; ¹H-NMR (500MHz, DMSO-d ₆) δ 14.70 (1H, s, NH); (8.45 1H, s, NH); (8.34 1H, s, H-4); (8.27-8.29 1H, d, J=9Hz, H-8); (7.99 1H, s, CH=NNH); (7.81-7.83 1H, m, H-5); (7.66-7.72 1H, m, H-7); 7.35-7.40 (2H, m,, CH=N, H-6); 4.70-4.75 (2H, s, NCH ₂CH ₃); 3.12 (3H, s, CH ₃); 1.35-1.42 (3H, m, NCH ₂CH ₃).

An embodiment A-12 (this synthetic route has been carried out some deletions)!

The general synthesis technique of 3-methylol-9-alkyl-1-(3,4,5-trimethoxy) phenyl-B-carboline (247-249):

9-replacement-1-(3,4, the 5-trimethoxy) phenyl-B-carboline-3-carboxylic acid, ethyl ester (10mmol), THF (200ml), LiBH4(30mmol) after the mixing, the about 10h of stirring at room reaction, TLC (petroleum ether/acetone=1/1) follows the tracks of detection, reacts complete, reaction mixture is slowly poured in the 200ml frozen water, stirring reaction 10min drips concentrated hydrochloric acid to pH2-3, stirring at room 10h, mixture water cooling on the rocks, sodium hydroxide solution is regulated pH value to 9, ethyl acetate extraction, washing, the saturated common salt washing, anhydrous sodium sulfate drying, decolorizing with activated carbon filters in (silica gel), be concentrated into dried, acetone solution, the refrigerator recrystallization gets white needle-like crystals.

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-methylol-9-methyl-B-carboline (247): with ethyl

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-methyl-B-carboline-3-carboxylate is raw material, gets white crystal 3.0g, yield 79%, mp 151-153 ℃; FAB-MS m/e (M+1) 379; IR (KBr) 3275,3060,2998,2930,2833,1622,1581,1504,1462,1413,1370,1234,1126,1063,1003,836,738; ¹H-NMR (500MHz, CDCl ₃) δ 8.30-8.32 (1H, d, J=10.0Hz, H-4); (8.19 1H, s, H-6); (7.60-7.61 2H, m, H-5, H-8); (7.27-7.31 1H, m, H-7); (6.86 2H, s, PhH); 4.73-4.75 (2H, d, J=7.0Hz, CH ₂OH); 3.82 (6H, s, OCH ₃); 3.76 (3H, s, OCH ₃); 3.50 (3H, s, NCH ₃).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-methylol-9-ethyl-B-carboline (248): with ethyl 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-ethyl-B-carboline-3-carboxylate is raw material, gets white crystal 2.9g, yield 74%, mp 154-155 ℃; FAB-MS m/e (M+1) 393; IR (KBr) 3328,3068,2968,2936,2835,1621,1582,1504,1450,1410,1370,1231,1125,1052,1013,832,742; ¹H-NMR (500MHz, CDCl ₃) δ 8.30-8.32 (1H, d, J=10.5Hz, H-4); (8.20 1H, s, H-6); (7.57-7.65 2H, m, H-5, H-8); (7.26-7.30 1H, m, H-7); (6.86 2H, s, PhH); 4.73-4.74 (2H, d, J=7.0Hz, CH ₂OH); 4.02-4.07 (2H, s, NCH ₂CH ₃); 3.81 (6H, s, OCH ₃); 3.77 (3H, s, OCH ₃); 0.93-0.97 (3H, m, NCH ₂CH ₃).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-methylol-9-normal-butyl-B-carboline (249): with ethyl 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-normal-butyl-B-carboline-3-carboxylate is raw material, get white crystal 3.2g, yield 76%, mp 127-128 ℃; FAB-MS m/e (M+1) 421; IR (KBr) 3338,3181,3061,2986,2832,1621,1583,1505,1465,1409,1366,1297,1235,1179,1126,1051,998,833,739; ¹H-NMR (500MHz, CDCl ₃) δ 8.30-8.31 (1H, d, J=10.5Hz, H-4); (8.20 1H, s, H-6); (7.57-7.65 2H, m, H-5, H-8); (7.25-7.29 1H, m, H-7); (6.84 2H, s, PhH); 4.72-4.74 (2H, d, J=7.0Hz, CH ₂OH); 3.93-3.97 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 3.80 (6H, s, OCH ₃); 3.75 (3H, s, OCH ₃); 1.31-1.39 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.86-0.92 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.62-0.66 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

The general synthesis technique of 3-aldehyde radical-9-replacement-1-(3 ', 4 ', 5 '-trimethoxy) phenyl-B-carboline (250-252):

3-methylol-9-alkyl-1-(3 ', 4 ', 5 '-trimethoxy) phenyl-B-carboline 143-146 (10mmol), acetonitrile (250ml), active MnO ₂(100mmol) mix, the about 1h of reflux, TLC follows the tracks of detection.React complete, remove by filter immediately MnO ₂, be evaporated to driedly, get yellow solid.Solid is dissolved in ethyl acetate, and activated carbon decolorizing is crossed silica gel, concentrating under reduced pressure, and acetone recrystallization gets white crystal.

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-aldehyde radical-9-methyl-B-carboline (250): with 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-methylol-9-methyl-B-carboline is raw material, gets white crystal 2.8g, yield 74%, mp 200-201 ℃; FAB-MS m/e (M+1) 377; IR (KBr) 3057,2986,2939,2815,1620,1684,1585,1501,1463,1367,1238,1123,997,837,740; ¹H-NMR (500MHz, CDCl ₃) δ 10.27 (1H, s, CHO); (8.76 1H, s, H-4); (8.25-8.27 1H, d, J=9.5Hz, H-6); (7.66-7.70 1H, m, H-5); (7.49-7.51 1H, d, J=9.5Hz, H-8); (7.40-7.44 1H, m, H-7); (6.84 2H, s, PhH); 3.94 (3H, s, OCH ₃); 3.92 (6H, s, OCH ₃); 3.59 (3H, s, NCH ₃).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-aldehyde radical-9-ethyl-B-carboline (251): with 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-methylol-9-ethyl-B-carboline is raw material, gets white crystal 3.2g, yield 82%, mp 209-210 ℃; FAB-MS m/e (M+1) 391; IR (KBr) 3065,3001,2935,2829,1687,1621,1580,1503,1457,1404,1325,1233,1127,1008,865,743; ¹H-NMR (500MHz, CDCl ₃) δ 10.27 (1H, s, CHO); (8.77 1H, s, H-4); (8.26-8.28 1H, d, J=9.5Hz, H-6); (7.67-7.69 1H, m, H-5); (7.50-7.53 1H, d, J=10.5Hz, H-8); (7.39-7.43 1H, m, H-7); (6.84 2H, s, PhH); 4.07-4.12 (2H, m, NCH ₂CH ₃); 3.94 (3H, s, OCH ₃); 3.91 (6H, s, OCH ₃); 3.59 (3H, s, NCH ₃); 1.12-1.15 (3H, m, NCH ₂CH ₃).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-aldehyde radical-9-normal-butyl-B-carboline (252): with 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-methylol-9-normal-butyl-B-carboline is raw material, gets white crystal 3.0g, yield 72%, mp 150-151 ℃; FAB-MS m/e (M+1) 419; IR (KBr) 3059,3002,2958,2809,1694,1618,1582,1505,1464,1410,1363,1244,1203,1124,1001,969,851,754; ¹H-NMR (500MHz, CDCl ₃) δ 10.26 (1H, s, CHO); (8.76 1H, s, H-4); (8.25-8.27 1H, d, J=10.0Hz, H-6); (7.64-7.68 1H, m, H-5); (7.49-7.51 1H, d, J=10.5Hz, H-8); (7.38-7.42 1H, m, H-7); (6.84 2H, s, PhH); 3.98-4.02 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 3.93 (3H, s, OCH ₃); 3.91 (6H, s, OCH ₃); 1.48-1.56 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.96-1.06 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.73-0.76 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

Synthesizing of 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-alkyl-B-carboline-3-aldehyde radical thiosemicarbazones (253-255)

3-aldehyde radical-9-replacement-1-(3 ', 4 ', 5 '-trimethoxy) phenyl-B-carboline (2mmol), thiosemicarbazides (2mmol), dehydrated alcohol (100ml) mix, reflux 24 hours, be cooled to room temperature, allow ethanol naturally volatilize, separate out yellow crystals.The dehydrated alcohol recrystallization gets yellow solid.

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-methyl-B-carboline-3-aldehyde radical thiosemicarbazones (253): with 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-aldehyde radical-9-methyl-B-carboline is raw material, gets yellow solid 0.62g, yield 69%, mp 240-242 ℃; FAB-MS m/e (M+1) 450; IR (KBr) 3408,3280,3163,2939,2831,1586,1497,1463,1410,1362,1323,1298,1235,1124,1041,1009,841,751; ¹H-NMR (500MHz, DMSO-d ₆) δ 11.59 (1H, s); (9.10 1H, s); (8.26-8.37 3H, m); (8.13 1H, s, H-5); (7.65-7.66 2H, d, J=10.5Hz); (7.35-7.39 1H, m); (6.90 2H, s); (3.83 6H, s); (3.79 3H, s); (3.30 3H, s).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-ethyl-B-carboline-3-aldehyde radical thiosemicarbazones (254): with 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-aldehyde radical-9-ethyl-B-carboline is raw material, gets yellow solid 0.68g, yield 73%, mp 199-200 ℃; FAB-MS m/e (M+1) 464; IR (KBr) 3398,3248,3152,2972,2934,2832,1584,1502,1436,1349,1231,1126,1007,849,740; ¹H-NMR (500MHz, DMSO-d ₆) δ 11.57 (1H, s); (9.09 1H, s); (8.25-8.37 3H, m); (8.11 1H, s); (7.62-7.66 2H, d, J=10.5Hz); (7.34-7.37 1H, m); (6.89 2H, s); (4.25-4.30 2H, m); (3.91 9H, s); (0.97 3H, s).

1-(3 ', 4 ', 5 '-trimethoxy) phenyl-9-normal-butyl-B-carboline-3-aldehyde radical thiosemicarbazones (255): with 1-(3 ', 4 ', 5 '-trimethoxy) phenyl-3-aldehyde radical-9-normal-butyl-B-carboline is raw material, get yellow solid 0.73g, yield 74%, mp 145-147 ℃; FAB-MS m/e (M+1) 492; IR (KBr) 3525,3351,3150,2958,2936,2827,1618,1572,1538,1503,1462,1436,1332,1233,1127,1098,978,834,733; ¹H-NMR (500MHz, DMSO-d ₆) δ 11.59 (1H, s); (9.10 1H, s); (8.26-8.35 3H, m); (8.13 1H, s); (7.61-7.70 2H, d, J=10.5Hz); (7.33-7.37 1H, m, H-6); (6.88 2H, s); (3.93-3.97 2H, m); (3.81 6H, s); (3.77 3H, s); (1.36-1.42 2H, m); (0.89-0.95 2H, m); (0.64-0.68 2H, m).

An embodiment A-13 (this synthetic route has been carried out some deletions)!

The general synthesis technique (256-258) of 1-styryl-beta-carboline derivatives:

B-carboline (10mmol), acetic anhydride (50ml) and corresponding aldehyde (20-100mmol) mix, stirring at room 30min, and then reflux 48-72 hour, TLC followed the tracks of detection; React complete, pour in the 200ml cold water after reactant liquor is cooled to room temperature, the sodium bicarbonate alkalization, ethyl acetate extraction merges organic facies, washing, the saturated salt washing, anhydrous sodium sulfate drying filters, concentrating under reduced pressure, residue is dissolved in dehydrated alcohol, regulates pH to 1～2 with the Hydrochlorine-Ethanol saturated solution, be evaporated to dried, the residue acetone recrystallization filters, and gets yellow solid.Yellow solid is dissolved in 50ml water, the sodium bicarbonate alkalization, ethyl acetate extraction merges organic facies, washing, the saturated salt washing, anhydrous sodium sulfate drying filters concentrating under reduced pressure, residue silica gel column chromatography, acetone/petroleum ether (1/2) recrystallization.

1-(4 '-nitro-styryl)-and 9-acetyl group-B-carboline (256) synthetic: take 1-methyl-B-carboline and 4-nitrobenzaldehyde as raw material, get light yellow crystal 2.0g, yield 56%, mp 200-201 ℃.FAB-MSm/e(M+1)358;IR(KBr)3362,3067,1689,1614,1594,1516,1342,1203,1110,973,837,742； ¹H-NMR(500MHz,CDCl ₃)δ8.70-8.71(1H,d);8.15-8.17(1H,d);8.07-8.09(1H,d);7.95-7.97(1H,d);7.84-7.85(1H,d);7.65-7.78(3H,m);7.49-7.53(2H,m);7.29(2H,s);2.74(3H,s).

1-(4 '-nitro-styryl)-and 9-phenylpropyl-B-carboline (257) synthetic: take 9-phenylpropyl-1-methyl-B-carboline and 4-nitrobenzaldehyde as raw material, get light red acicular crystal 2.8g, yield 65%, mp179-180 ℃.FAB-MS?m/e(M+1)434;IR(KBr)3051,3027,2932,2899,1593,1506,1469,1445,1419,1335,1222,1154,1108,968,836； ¹H-NMR(500MHz,CDCl ₃)δ8.52-8.53(1H,d);8.15-8.17(1H,d);7.92-7.97(3H,m);7.66-7.69(3H,m);7.16-7.30(7H,m);7.16-7.19(2H,d);4.60-4.64(2H,t);2.78-2.82(2H,m);1.60-1.62(2H,m)

1-(4 '-nitro-styryl)-7-n-butoxy-9-phenylpropyl-B-carboline (258) synthetic: take 7-n-butoxy-9-phenylpropyl-1-methyl-B-carboline and 4-nitrobenzaldehyde as raw material, get light red acicular crystal 3.2g, yield 63%, mp170-171 ℃; FAB-MS m/e (M+1) 506; IR (KBr) 3056,3028,2958,2933,2869,1617,1590,1506,1422,1334,1229,1157,1107,1042,965,814; ¹H-NMR (500MHz, CDCl ₃) δ 8.47-8.48 (1H, d); (8.26-8.28 1H, d); (7.98-8.00 1H, d); (7.67-7.91 5H, m); (7.19-7.33 6H, m); (6.90-6.93 1H, dd); (6.70 1H, s); (4.51-4.54 2H, t); (4.01-4.05 2H, t); (2.79-2.82 2H, t); (2.31-2.35 2H, m); (1.84-1.88 2H, m); (1.56-1.60 2H, m); (1.04-1.07 3H, t).

The 1-(styryl)-the general synthesis technique of 2-benzyl-B-carboline bromine salt (259-260): the 1-(styryl)-B-carboline (2mmol), ethyl acetate (50ml) and cylite (10-20mmol) mix, reflux 2-4 hour, the cooling reactant liquor is to room temperature, filter, the ethyl acetate washing gets yellow solid.Yellow solid is dissolved in the 50ml dehydrated alcohol, and reflux is to clarification, and filtered while hot is cooled to room temperature, the refrigerator recrystallization.1-(4 '-nitro-styryl)-9-acetyl group-2-benzyl-B-carboline bromine salt (259) synthetic: take 1-(4 '-nitro-styryl)-9-acetyl group-B-carboline is raw material, gets yellow particle shape crystal 0.8g, yield 76%, mp〉250 ℃.FAB-MS?m/e?448;IR(KBr)3408,3007,2978,2894,1731,1618,1514,1453,1423,1343,1242,1157,976,837； ¹H-NMR(500MHz,DMSO-d ₆)δ9.23-9.25(1H,d);8.98-8.99(1H,d);8.63-8.65(1H,m);8.29-8.38(2H,m);7.68-8.16(6H,m);7.10-7.31(6H,m);3.30(3H,s)

1-(4 '-nitro-styryl)-7-n-butoxy-9-phenylpropyl-2-benzyl-B-carboline bromine salt (260) synthetic: take 1-(4 '-nitro-styryl)-7-n-butoxy-9-phenylpropyl-B-carboline is raw material, get yellow particle shape crystal 0.9g, yield 66%, mp 228-229 ℃.FAB-MS?m/e?596;IR(KBr)3046,3027,2954,2930,2867,1619,1522,1454,1431,1345,1231,1138,1061,971,836； ¹H-NMR(500MHz,DMSO-d ₆)δ8.92-8.93(1H,d,H-3);8.74-8.76(1H,d);8.43-8.45(1H,d);8.31-8.34(2H,m);7.86-8.01(3H,m);7.08-7.33(11H,m)6.86-6.88(2H,dd);6.01(2H,s);4.49-4.53(2H,m,2H,t);4.17-4.20(2H,t);2.29-2.33(2H,t,2H,m);1.78-1.90(4H,m);1.48-1.54((2H,m);0.96-1.00(3H,t).

Embodiment A-14

The general synthesis technique (261-263) of 9 alkylated reactions:

With B-carboline (0.84g, 5.0mmol), DMF (30ml), 60% sodium hydride (0.6g, 15mmol) mix, and stirs 15min under the room temperature, add subsequently corresponding halogenated alkane (20mmol), stirring reaction 2 hours, TLC are followed the tracks of and are detected (developing solvent: acetone/petroleum ether=1:1), react complete, reactant mixture is poured into water, ethyl acetate extraction, washing, saturated salt washing.Organic facies concentrated hydrochloric acid acidify, be evaporated to dried, dehydrated alcohol band water twice, the residue acetone recrystallization filters, and gets yellow solid.Yellow solid is water-soluble, saturated solution of sodium bicarbonate alkalization, ethyl acetate extraction, washing, saturated salt washing, drying, activated carbon decolorizing filters concentrating under reduced pressure, column chromatography, ethyl acetate/petroleum ether=5:1 makes mobile phase, collects target product, is evaporated to driedly, gets target product.

Synthetic (261) of 9-pi-allyl-B-carboline

Take allyl bromide, bromoallylene as raw material, get white solid (0.65g, 63%), ¹H NMR (300MHz, CDCl ₃) δ 8.85 (s, 1H, ArH); (8.47 d, J=6.5Hz, 1H, ArH); (8.16 d, J=8.0Hz, 1H, ArH); (7.98 d, J=5.1Hz, 1H, ArH); (7.59 t, J=7.2Hz, 1H, ArH); (7.46 d, J=8.4Hz, 1H, ArH); (7.29 t, J=7.2Hz, 1H, ArH); 6.07-5.92 (m, 1H, NCH ₂CH=CH ₂); 5.23-5.03 (m, 2H, NCH ₂CH=CH ₂); 5.03-5.98 (m, 2H, NCH ₂CH=CH ₂).

Synthetic (262) of 9-isobutyl group-B-carboline

Take isobutyl bromide as raw material, get white solid (0.82g, 73%), ¹H NMR (300MHz, CDCl ₃) δ 8.87 (s, 1H, ArH); (8.45 d, J=5.4Hz, 1H, ArH); (8.15 d, J=8.1Hz, 1H, ArH); (7.96 d, J=5.4Hz, 1H, ArH); (7.58 t, J=7.2Hz, 1H, ArH); (7.47 d, J=5.1Hz, 1H, ArH); (7.30-7.25 m, 1H, ArH); 4.18 (d, J=7.5Hz, 2H, NCH ₂CH (CH ₃) ₂); 2.47-2.33 (m, 1H, NCH ₂CH (CH ₃) ₂); 1.00 (d, J=6.6Hz, 6H, NCH ₂CH (CH ₃) ₂)

Synthetic (263) of 9-hexyl-B-carboline

Take hexyl bromide 1 bromohexane as raw material, get yellow oil (1.02g, 79%), ¹H NMR (300MHz, CDCl ₃) δ 8.87 (s, J=8.0Hz, 1H, ArH); (8.45 d, J=6.3Hz, 1H, ArH); (7.94 d, J=5.4Hz, 1H, ArH); (7.57 t, J=8.1Hz, 1H, ArH); (7.45 d, J=8.1Hz, 1H, ArH); (7.25 m, 1H, ArH); 4.33 (t, J=7.2Hz, 2H, NCH ₂CH ₂C ₃H ₆CH ₃); 1.89 (m, 2H, NCH ₂CH ₂C ₃H ₆CH ₃); 1.30 (m, 6H, NCH ₂CH ₂C ₃H ₆CH ₃); 0.86 (t, J=6.9Hz, 3H, NCH ₂CH ₂C ₃H ₆CH ₃).

Embodiment A-15

The general synthesis technique of B-carboline bromine salt (264-271)

Add 9-alkyl-B-carboline (2mmol), cylite (10mmol) and ethyl acetate (50mL) in the 100ml round-bottomed flask, stir lower heating reflux reaction 5h. cooling reactant liquor to room temperature, filter, the ethyl acetate washing gets yellow solid.Yellow solid is dissolved in the 50ml dehydrated alcohol, and reflux is to clarification, and filtered while hot is cooled to room temperature, and the refrigerator recrystallization gets yellow solid.

2-benzyl-9-methyl-B-carboline bromine salt (264)

Take 9-methyl-B-carboline as raw material, get yellow solid (0.49g, 90%), ESI-MS 273.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO-d ₆) δ 9.85 (s, 1H, ArH); (8.80 q, J=6.5Hz, 2H, ArH); (8.48 d, J=8.0Hz, 1H, ArH); (7.87 q, J=8.7Hz, 3H, ArH); (7.61-7.27 m, 6H, ArH); 5.93 (s, 2H, N ⁺CH ₂Ph); 4.09 (s, 3H, NCH ₃). ¹³C NMR (500MHz, DMSO-d ₆) δ 145.1,136.5,135.5,132.8,132.7,132.1,129.7,129.6,129.1,129.0,124.0,122.3,119.2,118.5,111.6,63.8,30.9.

2 benzyls-9-ethyl-B-carboline bromine salt (265)

Take 9-ethyl-B-carboline as raw material, get yellow solid (0.55g, 96%), ESI-MS 287.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO-d ₆) δ 9.89 (s, 1H, ArH); (8.79 q, J=14.8Hz, 2H, ArH); (8.50 d, J=8.0Hz, 1H, ArH); 7.97 – 7.82 (m, 3H, ArH); 7.65 – 7.35 (m, 5H, ArH); 5.92 (s, 2H, N ⁺CH ₂Ph); 4.66 (q, J=7.0Hz, 2H, NCH ₂CH ₃); 1.41 (t, J=7.1Hz, 3H, NCH ₂CH ₃). ¹³C NMR (500MHz, DMSO) δ 144.3,135.6,135.6,133.0,132.9,132.5,129.6,129.1,128.8,124.4,122.4,119.5,118.7,111.7,63.9,14.4.

2-benzyl-9-isopropyl-B-carboline bromine salt (266)

Take 9-isopropyl-B-carboline as raw material, get yellow solid (0.58g, 97%), ESI-MS 301.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.87 (s, 1H, ArH); (8.82 d, J=6.4Hz, 1H, ArH); (8.75 d, J=6.4Hz, 1H, ArH); (8.50 d, J=8.0Hz, 1H, ArH); (8.03 d, J=8.5Hz, 1H, ArH); (7.83 t, J=7.9Hz, 1H, ArH); 7.56 – 7.36 (m, 6H, ArH); 5.94 (s, 2H, N ⁺CH ₂Ph); 5.35-5.26 (m, 1H, NCH (CH ₃) ₃) 1.71 (d, J=6.9Hz, 6H, NCH (CH ₃) ₃). ¹³CNMR (500MHz, DMSO) δ 143.8,135.7,134.9,132.9,132.8,132.7,129.6,129.5,128.9,124.4,122.3,119.9,118.606113.0,63.7,48.7,20.9.

2-benzyl-9-pi-allyl-B-carboline bromine salt (267)

Take 9-pi-allyl-B-carboline as raw material, get yellow solid (0.55g, 92%), ESI-MS 299.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.83 (s, 1H, ArH); (8.82 q, J=6.5Hz, 2H, ArH); (8.51 d, J=8.0Hz, 1H, ArH); 7.92 – 7.80 (m, 2H, ArH); (7.57-7.35 m, 6H, ArH); 6.11 – 5.97 (m, 1H, NCH ₂CH=CH ₂); 5.92 (s, 2H, N ⁺CH ₂Ph), 5.27 (d, J=5.2Hz, 2H, NCH ₂CH=CH ₂); 5.18-5.06 (m, 2H, NCH ₂CH=CH ₂). ¹³C NMR (500MHz, DMSO) δ 144.7,136.1,135.5,133.3,132.9,132.7,132.4,129.6,129.1,128.8,124.4,122.6,119.6,118.8,118.3,112.0,63.9,46.3.

2-benzyl-9-isobutyl group-B-carboline bromine salt (268)

Take 9-isobutyl group-B-carboline as raw material, get yellow solid (0.57g, 90%), ESI-MS 315.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.92 (s, 1H, ArH), 8.80 (d, J=13.9Hz, 2H, ArH), 8.50 (d, J=8.0Hz, 1H, ArH); (7.96 d, J=8.5Hz, 1H, ArH); (7.84 t, J=7.8 Hz, 1H, ArH); 7.57 – 7.34 (m, 6H, ArH); 5.93 (s, 2H, N ⁺CH ₂Ph); 4.43 (d, J=7.6Hz, 2H, NCH ₂CH (CH ₃) ₂); 2.37 – 2.24 (m, 1H, NCH ₂CH (CH ₃) ₂); 0.89 (d, J=6.6Hz, 6H, NCH ₂CH (CH ₃) ₂). ¹³C NMR (500MHz, DMSO) δ 145.0,136.4,135.7,132.9,132.7,132.2,129.6,129.4,128.8,124.2,122.3,119.3,118.7,112.2,63.6,50.9,28.9,20.2.2-benzyl-9-hexyl-B-carboline bromine salt (269)

Take 9-hexyl-B-carboline as raw material, get yellow solid (0.66g, 96%), ESI-MS 343.3m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.95 (s, 1H, ArH), (8.77 s, 2H, ArH), 8.43 (d, J=8.0Hz, 1H, ArH), 7.88 –, 7.75 (m, 2H, ArH), 7.57 (d, J=6.6Hz, 2H, ArH), 7.47 – 7.32 (m, 4H, ArH), 5.96 (s, 2H, N ⁺CH ₂Ph); 4.58 (t, J=6.9Hz, 2H, NCH ₂CH ₂C ₃H ₆CH ₃); 1.85 – 1.72 (m, 2H, NCH ₂CH ₂C ₃H ₆CH ₃); 1.26 – 1.05 (m, 6H, NCH ₂CH ₂C ₃H ₆CH ₃); 0.71 (t, J=6.8Hz, 3H, NCH ₂CH ₂C ₃H ₆CH ₃). ¹³C NMR (500MHz, DMSO) δ 144.7,136.1,135.6,132.9,132.8,132.3,129.6,129.0,128.8,124.3,122.4,119.4,118.7,111.8,63.7,44.2,31.2,29.0,26.3,22.3,14.2.

2-benzyl-9-octyl group-B-carboline bromine salt (270)

Take 9-octyl group-B-carboline as raw material, get yellow solid (0.64g, 86%), ESI-MS 371.3m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.92 (s, 1H, ArH); (8.81 q, J=6.5Hz, 2H, ArH); (8.49 d, J=8.0Hz, 1H, ArH); (7.87 dt, J=8.3Hz, 2H, ArH); (7.58-7.35 m, 6H, ArH); 5.94 (s, 2H, N ⁺CH ₂Ph); 4.61 (t, J=6.9Hz, 2H, NCH ₂CH ₂C ₅H ₁₀CH ₃); 1.84-1.80 (m, 2H, NCH ₂CH ₂C ₅H ₁₀CH ₃) 1.16 (m, 10H, NCH ₂CH ₂C ₅H ₁₀CH ₃); 0.77 (t, J=6.8Hz, 3H, NCH ₂CH ₂C ₅H ₁₀CH ₃). ¹³C NMR (500MHz, DMSO) δ 144.6,136.1,135.7,132.9,132.8,132.3,129.6,129.1,128.8,124.3,122.4,119.4,118.7,111.8,63.7,44.2,31.5,29.1,28.9,26.7,22.4,14.3.

2-benzyl-9-(4-luorobenzyl)-B-carboline bromine salt (271)

Take the 9-(4-luorobenzyl)-B-carboline is raw material, gets yellow solid (0.67g, 91%), ESI-MS 367.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.97 (s, 1H, ArH), 8.86 (s, 2H, ArH), 8.51 (d, J=8.0Hz, 1H, ArH); (7.91 d, J=8.5Hz, 1H, ArH); (7.81 d, J=11.4Hz, 1H, ArH); 7.58 – 7.29 (m, 8H), ArH; 7.16 – 7.06 (m, 2H, ArH); 5.94 (s, 2H, N ⁺CH ₂Ph); 5.87 (s, 2H, NCH ₂Ph (p-F)). ¹³C NMR (500MHz, DMSO) δ 163.4,161.0,144.6,136.3,135.6,133.6,133.0,132.9,132.6,129.9,129.8,129.6,129.1,128.9,124.5122.7,119.8,118.9,116.2,116.0,112.1,63.9,46.7.

Embodiment A-16

The general synthesis technique of B-carboline bromine salt (272-280)

Adding 9-(3-phenyl in the 100ml round-bottomed flask) propyl group-B-carboline (2mmol), halogenated alkane (20mmol) and ethyl acetate (50mL), stir lower heating reflux reaction 5h. cooling reactant liquor to room temperature, filter, the ethyl acetate washing gets yellow solid.Yellow solid is dissolved in the 50ml dehydrated alcohol, and reflux is to clarification, and filtered while hot is cooled to room temperature, and the refrigerator recrystallization gets yellow solid.

9-(3-phenyl) propyl group-2 methyl-B-carboline iodine salt (272)

Take iodomethane as raw material, get yellow solid (0.57g, 95%) were obtained, ESI-MS 301.2m/z[M-I] ⁺; ¹H NMR (300MHz, DMSO-d ₆) δ 9.54 (1H, s, ArH); (8.73 1H, d, J=6.4Hz, ArH); (8.58 1H, d, J=6.4Hz, ArH); (8.47 1H, d, J=8.0Hz, ArH); (7.84 2H, q, J=8.4Hz, ArH); (7.46 d, J=7.7Hz, 1H, ArH); 7.23 – 7.05 (m, 5H, ArH); 4.63 (t, J=7.0Hz, 2H, NCH ₂CH ₂CH ₂Ph); 4.47 (s, 3H, N ⁺CH ₃); 2.65 (t, J=7.5Hz, 2H, NCH ₂CH ₂CH ₂Ph); 2.23 – 2.10 (m, 2H, NCH ₂CH ₂CH ₂Ph). ¹³C NMR (500MHz, DMSO) δ 144.3,141.3,135.7,133.8,132.4,131.9,129.7,128.7,128.5,126.3,124.1,122.2,119.4,117.9,111.7,48.3,43.9,32.7,30.4..

9-(3-phenyl) propyl group-2-ethyl-B-carboline bromine salt (273)

Take bromoethane as raw material, get yellow solid (0.60g, 95%) were obtained, ESI-MS 315.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.64 (s, 1H, ArH), 8.78 (d, J=6.4Hz, 1H, ArH), 8.70 (d, J=6.5Hz, 1H, ArH), 8.49 (d, J=8.0Hz, 1H, ArH), 7.93 – 7.79 (m, 2H, ArH), 7.47 (t, J=7.3Hz, 1H, ArH), 7.19 – 7.04 (m, 5H, ArH), 4.73 (q, J=7.3Hz, 2H, NCH ₂CH ₂CH ₂Ph), 4.65 (t, J=7.1Hz, 2H, N ⁺CH ₂CH ₃), 2.66 (t, J=7.5Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.24 – 2.11 (m, 2H, NCH ₂CH ₂CH ₂Ph), 1.64 (t, J=7.2Hz, 3H, N ⁺CH ₂CH ₃). ¹³C NMR (500MHz, DMSO) δ 144.3,141.3,135.9,132.6,132.4,132.1,128.7,128.6,128.5,126.3,124.2,122.2,119.4,118.3,111.7,56.8,44.0,32.7,30.4,17.5.

9-(3-phenyl) propyl group-2-normal-butyl-B-carboline bromine salt (274)

Take bromination of n-butane as raw material, get yellow solid (0.64g, 93%) were obtained, ESI-MS343.2m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.65 (s, 1H, ArH), 8.78 (d, J=6.4Hz, 1H, ArH), 8.70 (d, J=6.4Hz, 1H, ArH), 8.49 (d, J=8.0Hz, 1H, ArH), 7.94-7.79 (m, 2H, ArH), 7.47 (t, J=7.3Hz, 1H, ArH), 7.12 (m, 5H, ArH), 4.72-4.63 (m, 4H, NCH ₂CH ₂CH ₂Ph, N ⁺CH ₂CH ₂CH ₂CH ₃), 2.65 (t, J=7.5Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.24-2.10 (m, 2H, NCH ₂CH ₂CH ₂Ph), 2.07-1.92 (m, 2H, N ⁺CH ₂CH ₂CH ₂CH ₃), 1.39-1.25 (m, 2H, N ⁺CH ₂CH ₂CH ₂CH ₃), 0.93 (t, J=7.3Hz, 3H, N ⁺CH ₂CH ₂CH ₂CH ₃). ¹³C NMR (500MHz, DMSO) δ 144.3,141.3,135.8,132.9,132.5,132.1,128.8,128.6,128.4,126.2,124.2,122.2,119.4,118.2,111.7,60.9,44.0,33.7,32.6,30.5,19.3,13.9.

9-(3-phenyl) propyl group-2-n-hexyl-B-carboline bromine salt (275)

Take the bromo normal hexane as raw material, get yellow solid (0.56g, 76%), ESI-MS 371.3m/z M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.75 (s, 1H, ArH), 8.72 (d, J=6.3Hz, 1H, ArH), 8.66 (d, J=6.4Hz, 1H, ArH), 8.42 (d, J=8.0Hz, 1H, ArH), 7.85 – 7.73 (m, 2H, ArH), 7.48 –, 7.36 (t, J=7.8Hz 1H, ArH), 7.07 (m, 5H, ArH), 4.71 (t, J=7.1Hz, 2H, N ⁺CH ₂C ₃H ₆CH ₂CH ₃), 4.63 (t, J=6.8Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.64 (t, J=7.2Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.19 – 2.05 (m, 2H, NCH ₂CH ₂CH ₂Ph), 1.95 (m, 2H, N ⁺CH ₂C ₃H ₆CH ₂CH ₃), 1.31-1.21 (m, 6H, N ⁺CH ₂C ₃H ₆CH ₂CH ₃), 0.75 (t, J=6.6Hz, 3H, N ⁺CH ₂C ₃H ₆CH ₂CH ₃). ¹³C NMR (101MHz, DMSO) δ 144.4,141.3,136.0,133.0,132.6,132.2,128.9,128.6,128.4,126.3,124.2,122.3,119.5,118.2,111.7,61.2,43.9,32.7,31.6,31.0,30.5,25.6,22.3,14.2.

9-(3-phenyl) propyl group-2-n-octyl-B-carboline iodine salt (276)

Take the iodo normal octane as raw material, get yellow solid (0.38g, 47%), ESI-MS 399.4m/z[[M-I] ⁺; ¹H NMR (300MHz, DMSO) δ 9.64 (s, 1H, ArH), 8.78 (d, J=6.4Hz, 1H, ArH), 8.69 (d, J=6.4Hz, 1H, ArH), 8.49 (d, J=8.0Hz, 1H, ArH), 7.96 – 7.78 (m, 3H, ArH), 7.48 (t, J=7.3Hz, 1H, ArH), 7.12 (m, 5H, ArH), 4.70 (d, J=6.7Hz, 2H, N ⁺CH ₂C ₅H ₁₀CH ₂CH ₃), 4.65 (d, J=6.5Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.64 (t, J=7.5Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.24 – 2.10 (m, 2H, NCH ₂CH ₂CH ₂Ph), 2.02-1.96 (m, 2H, N ⁺CH ₂C ₅H ₁₀CH ₂CH ₃), 1.20 (m, 10H, N ⁺CH ₂C ₅H ₁₀CH ₂CH ₃), 0.78 (t, J=6.7Hz, 3H, N ⁺CH ₂C ₅H ₁₀CH ₂CH ₃). ¹³C NMR (500MHz, DMSO) δ 144.4,141.3,135.9,133.0,132.5,132.2,128.9,128.6,128.4,126.3,124.2,122.2,119.5,118.3,111.7,61.2,44.0,32.7,31.7,31.5,30.5,28.9,28.8,25.9,22.4,14.3.

The positive decyl of 9-(3-phenyl) propyl group-2--B-carboline iodine salt (277)

Take the iodo n-decane as raw material, get yellow solid (0.39g, 46%), ESI-MS 427.4m/z[[M-I] ⁺; ¹H NMR (300MHz, DMSO) δ 9.79 (s, 1H, ArH), 8.69 (m, 2H, ArH), 8.38 (d, J=8.0 Hz, 1H, ArH), 7.74 (m, 2H, ArH), 7.36 (t, J=7.1Hz, 1H, ArH), 7.12 – 6.93 (m, 5H, ArH), 4.74 (t, J=7.0Hz, 2H, N ⁺CH ₂C ₇H ₁₄CH ₂CH ₃), 4.61 (t, J=6.8Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.62 (t, J=7.5Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.11-1.95 (m, 4H, NCH ₂CH ₂CH ₂Ph, N ⁺CH ₂C ₇H ₁₄CH ₂CH ₃), 1.10 (m, 14H, N ⁺CH ₂C ₇H ₁₄CH ₂CH ₃), 0.65 (t, J=6.6Hz, 3H, N ⁺CH ₂C ₇H ₁₄CH ₂CH ₃). ¹³C NMR (500MHz, DMSO) δ 149.1,146.3,146.2,140.6,137.8,137.4,137.0,133.9,133.4,133.3,131.1,129.1,127.1,124.3,123.2,116.6,66.1,49.1,37.7,36.7,35.8,34.3,34.1,34.0,31.0,27.5,19.4.

9-(3-phenyl) propyl group-2-(4-luorobenzyl)-B-carboline bromine salt (278)

Take 4-fluorine cylite as raw material, get yellow solid (0.61g, 77%) were obtained, ESI-MS 395.3m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.97 (s, 1H, ArH), 8.84 – 8.74 (m, 2H, ArH), 8.46 (d, J=8.0Hz, 1H, ArH), 7.92 – 7.79 (m, 2H, ArH), 7.70 (m, 2H, ArH), 7.46 (t, J=7.3Hz, 1H, ArH), (7.26 t, J=8.8Hz, 2H, ArH), 7.14 –, 6.95 (m, 5H, ArH), 5.93 (s, 2H, N ⁺CH ₂Ph (p-F)), 4.69 (t, J=6.8Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.64 (t, J=7.2Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.27 – 2.09 (m, 2H, NCH ₂CH ₂CH ₂Ph). ¹³C NMR (500MHz, DMSO) δ 144.7,141.2,136.1,132.7,132.0,131.5,129.3,128.6,128.3,126.2,124.3,122.4,119.5,118.6,116.5,116.3,111.8,62.9,44.1,32.7,30.3.

9-(3-phenyl) propyl group-2-(phenethyl)-B-carboline bromine salt (279)

Take the Beta-bromo vinylbenzene as raw material, get yellow solid (0.34g, 43%), ESI-MS 391.3m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.52 (s, 1H, ArH), 8.75 (d, J=6.4Hz, 1H, ArH), 8.64 (d, J=6.5Hz, 1H, ArH), 8.47 (d, J=8.0Hz, 1H, ArH), (7.85 q, J=8.4Hz, 2H, ArH), 7.46 (t, J=6.6Hz, 1H, ArH), 7.25-7.01 (m, 10H, ArH), 4.97 (t, J=7.0Hz, 2H, N ⁺CH ₂CH ₂Ph), 4.59 (t, J=7.0Hz, 2H, NCH ₂CH ₂CH ₂Ph), 3.36 (t, J=7.0Hz, 2H, N ⁺CH ₂CH ₂Ph), 2.58 (t, J=7.8Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.09-1.99 (m, 2H, NCH ₂CH ₂CH ₂Ph). ¹³C NMR (500MHz, DMSO) δ 144.4,141.3,136.7,135.6,133.0,132.6,132.1,129.3,129.0,128.7,128.5,127.4,126.3,124.2,122.3,119.4,118.1,111.7,61.9,43.9,37.4,32.7,30.5.

9-(3-phenyl) propyl group-2-(3-phenyl) propyl group-B-carboline bromine salt (280)

Take 1-bromo-3-phenyl-propane as raw material, get yellow solid (0.31g, 38%), ESI-MS 405.3m/z[M-Br] ⁺; ¹H NMR (300MHz, DMSO) δ 9.90 (s, 1H, ArH), (8.70 m, 2H, ArH), 8.37 (d, J=8.0Hz, 1H, ArH), 7.80 –, 7.64 (m, 2H, ArH), 7.34 (m, 1H, ArH), 7.16 – 6.90 (m, 10H, ArH), 4.85 (t, J=7.0Hz, 2H, N ⁺CH ₂CH ₂CH ₂Ph), 4.59 (t, J=6.8Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.67 (t, J=7.1Hz, 2H, N ⁺CH ₂CH ₂CH ₂Ph), 2.62 (t, J=7.5Hz, 2H, NCH ₂CH ₂CH ₂Ph), 2.40-2.31 (m, 2H, N ⁺CH ₂CH ₂CH ₂Ph), 2.21-2.11 (m, 2H, NCH ₂CH ₂CH ₂Ph). ¹³C NMR (500MHz, DMSO) δ 144.3,141.4,140.87,135.8,133.0,132.4,132.1,129.0,128.7,128.6,128.5,128.4,126.3,126.2,124.2,122.1,119.4,118.2,111.6,60.9,43.9,33.2,32.6,32.2,30.6.

Embodiment B-1:

9-replaces the general synthesis technique (300-304) of beta-carboline alkaloid derivant:

Get B-carboline (10mmol) and place the 100ml round-bottomed flask, add drying tube on the flask, add 80mlDMF, magnetic agitation is to dissolving, place ice-water bath, add sodium hydride (15mmol), the question response liquid cooling but adds corresponding alkyl halide (12mmol) afterwards.TLC monitoring reaction process (take ethyl acetate as developing solvent, detecting once in per 5 minutes).After about 1 hour, after TLC detects the raw material complete reaction, pour in the saturated NaOH water of about 50ml reactant liquor into stirring 3 hours, then divide four extractions with about 300ml ethyl acetate.Organic facies once added anhydrous sodium sulfate drying about 5 hours with about 100ml washing twice, the saturated sodium chloride washing of about 100ml, after be concentrated into dried, add the 40ml ether, solution is crossed silica gel G except the impurity of dereaction, an amount of ether washing silica gel G, be concentrated into and left in a small amount of liquid, cold preservation is filtered to there being crystal to occur, and insoluble matter is washed once with petroleum ether, the ether recrystallization obtains powdery product.

9-(3-chlorobenzyl)-B-carboline (300): take B-carboline and 3-chlorine cylite as raw material, get white crystal, yield 84.7%, m.p.94-95 ℃; MS m/e 292; IR (KBr) ν: 1650-3050,1622.9,1574.7,1560.0,1471.0,1447.3,1325.9,1200.7,1127.4,1077.6,1030.8,802.3,778.1,755.9,703.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.83 (1H, s, H-4); (8.50-8.52 1H, d, H-1); (8.19-8.21 1H, d, H-8); (8.01-8.02 1H, d, H-3); (7.59-7.61 1H, t, H-5); (7.41-7.43 1H, d, H-6); (7.32-7.34 1H, t, H-7); (7.16-7.24 3H, m, PhH); (7.00-7.02 1H, d, PhH); 5.50-5.56 (2H, m, NCH ₂Ph).

9-n-octyl-B-carboline (301): take B-carboline and iodo normal octane as raw material, get yellow solid, yield 75%, m.p.39-40 ℃; MS m/e 281; IR (KBr) ν: 1650-3050,1625.1,1589.2,1560.1,1493.9,1470.9,1453.2,1365.4,1348.5,1328.8,1275.9,1247.2,1228.4,1175.1,1153.0,1129.9,1075.4,1029.7,815.8cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.90-8.90 (1H, s, H-1); (8.46-8.47 1H, d, H-3); (8.15-8.17 1H, d, H-8); (7.97-7.99 1H, d, H-4); (7.63-7.59 1H, t, H-5); (7.47-7.49 1H, d, H-6); (7.28-7.32 1H, m, H-7); 4.36-4.40 (2H, m, NCH ₂(CH ₂) ₆CH ₃); 1.24-1.40 (15H, m, NCH ₂(CH ₂) ₆CH ₃).

9-(4-luorobenzyl)-B-carboline (302): take B-carboline and 4-fluorine cylite as raw material, get yellow crystals, yield 59.3%, m.p.98-99 ℃; MS m/e 276; IR (KBr) ν: 1650-3050,1623.6,1603.1,1557.5,1506.2,1470.3,1447.0,1413.4,1361.1,1330.1,1261.7,1221.2,1152.6,1130.6,1094.0,1069.8,1032.1,850.9,816.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.85 (1H, s, H-4); (8.50 1H, s, H-1); (8.18-8.21 1H, m, H-8); (8.03 1H, s, H-3); (7.58-7.62 1H, m, H-5); (7.44-7.46 1H, d, H-6); (7.32-7.36 1H, m, H-7); (7.12-7.21 2H, m, PhH); (6.92-7.00 2H, m, PhH); 5.51-5.56 (2H, d, NCH ₂Ph).

9-phenylpropyl-B-carboline (303): take B-carboline and 1-bromo-3-phenyl-propane as raw material, obtain white crystal, yield 74.3%, m.p.90-91 ℃; MS m/e 286; IR (KBr) ν: 1650-3050,1620.9,1584.9,1556.7,1491.8,1468.4,1447.4,1346.2,1328.6,1256.6,1217.4,1173.6,1149.8,1126.9,1024.2,819.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.82 (1H, s, H-4); (8.46-8.48 1H, d, H-1); (8.15-8.17 1H, d, H-8); (7.98-7.99 1H, d, H-3); (7.58-7.62 1H, t, H-5); (7.38-7.41 1H, d, H-6); (7.28-7.33 3H, m, H-7, PhH); (7.16-7.25 3H, m, PhH); 4.39-4.42 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.71-2.75 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.23-2.31 (2H, m, NCH ₂CH ₂CH ₂Ph)

9-(2,3,4,5,6-PFBBR)-B-carboline (304): be raw material with B-carboline and 2,3,4,5,6-, five fluorine cylites, get white crystal, yield 76.2%, m.p.132-133 ℃; MS m/e 348; IR (KBr) ν: 1650-3020,1625.7,1604.1,1555.6,1472.4,1446.1,1362.4,1331.7,1266.4,1153.2,1130.9,1096.4,1032.7,817.3cm ^-1; ¹H NMR (CDCl ₃, 400MHz) δ 8.87 (1H, s, H-4), 8.61-8.63 (1H, d, H-1), 8.52-8.54 (1H, d, H-8), 7.82-7.84 (1H, d, H-3), 7.52 (1H, m, H-5), (7.14 2H, m, H-6, H-7), 5.56 (s, 2H, NCH ₂Ph).

Embodiment B-2

Synthetic (305) of 9-acetyl group-B-carboline

Get 0.336g(2mmol) B-carboline places the 50ml round-bottomed flask, adds the acetic acid reflux of 15ml acetic anhydride and 5ml.TLC monitoring reaction process (every the 2-5min monitoring).After the raw material complete reaction, reactant liquor poured in the dilute sodium hydroxide water transfer to neutrality, be extracted in the water with ethyl acetate (500ml, minute 3 extractions) and have (with the TLC monitoring, onboard without product point existence) without product.Organic facies washes twice with water, and saturated sodium-chloride is washed once, adds anhydrous sodium sulfate drying, crosses silica gel G, uses the ethyl acetate rinse silica gel G, and the liquid under waiting to filter exists without product, stops flushing, filtrate is concentrated on a small quantity crystallisation by cooling.Filtration drying namely gets 9-acetyl group-B-carboline: ¹H NMR (DMSO-d ₆, 400MHz) δ 8.96 (1H, s, H-4), 8.62-8.64 (1H, d, H-1), 8.29-8.32 (2H, m, H-8, H-3), 8.18-8.20 (1H, d, H-5), 7.71-7.74 (1H, m, H-6), 7.37-7.39 (1H, m, H-7), 2.94 (3H, s, CH ₃).

Embodiment B-3

2,9-two replaces the general synthesis technique (306-322) of beta-carboline alkaloid derivant:

Take by weighing 9-and replace B-carboline (10mmol), add the 50ml ethyl acetate it is dissolved fully, add corresponding halogenated alkane (5-10mmol), reflux 8 hours, be cooled to room temperature, the solid that filtration is separated out, a small amount of ethyl acetate washing is dissolved in solid in the dehydrated alcohol subsequently, reflux is to clarification, filtered while hot is placed the refrigerator recrystallization, gets white or pale yellow crystals.

2,9-two (4-luorobenzyl)-B-carboline bromine salt (306): take 9-(4-fluorine) benzyl-B-carboline and 4-fluorine cylite as raw material, get yellow powder, yield 68.8%, m.p.271-273 ℃; MS m/e 385; IR (KBr) ν: 1650-3050,1639.1,1603.9,1576.2,1509.4,1465.6,1420.9,1392.2,1333.8,1268.5,1223.4,1161.9,1134.7,1102.6,1056.1,1015.4,831.4cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.99 (1H, s, H-4); (8.90 2H, s, H-1, H-8); (8.54-8.56 1H, d, H-3); (7.93-7.95 1H, d, H-5); (7.83-7.87 1H, t, H-6); (7.65-7.68 2H, m, H-7, PhH); (7.49-7.53 1H, t, PhH); (7.34-7.38 2H, m, PhH); (7.26-7.31 2H, t, PhH); (7.12-7.16 2H, m, PhH); 5.89-5.95 (4H, d, NCH ₂Ph).

9-(4-luorobenzyl)-2-benzyl-B-carboline bromine salt (307): take 9-(4-fluorine) benzyl-B-carboline and cylite as raw material, get yellow trichite, yield 81.2%, m.p.250-251 ℃; MS m/e 276; IR (KBr) ν: 1650-3050,1638.9,1602.9,1577.4,1508.2,1461.8,1392.9,1334.0,1299.9,1269.2,1215.5,1161.5,1135.9,1103.4,1056.4,1013.6,858.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.02 (1H, s, H-4); (8.92 2H, d, H-1, H-8); (8.55-8.57 1H, d, H-3); (7.95-7.97 1H, d, H-5); (7.84-7.88 1H, t, H-6); (7.35-7.57 8H, m, H-7, PhH); (7.12-7.17 2H, m, PhH); 5.90-5.96 (4H, d, NCH ₂Ph).

2,9-, two phenylpropyl-B-carboline bromine salt (308): take 9-phenylpropyl-B-carboline and 1-bromo-3-phenyl-propane as raw material, get yellow powder, yield 69.5%, MS m/e 276; IR (KBr) ν: 1650-3050,1638.9,1602.9,1577.4,1508.2,1461.8,1392.9,1334.0,1299.9,1269.2,1215.5,1161.5,1135.9,1103.4,1056.4,1013.6,858.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.73 (1H, s, H-4); (8.81-8.82 1H, d, H-1); (8.75-8.77 1H, d, H-8); (8.54-8.54 1H, d, H-3); (7.86-7.94 2H, m, H-5, H-6); (7.49-7.53 1H, t, H-7); (7.10-7.26 10H, m, Ph-H); 4.79-4.82 (2H, t, NCH ₂CH ₂CH ₂Ph); 4.67-4.71 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.66-2.72 (4H, m, NCH ₂CH ₂CH ₂Ph); 2.35-2.43 (2H, m, NCH ₂CH ₂CH ₂Ph); 2.17-2.23 (2H, m, NCH ₂CH ₂CH ₂Ph).

9-acetyl group-2-benzyl-B-carboline bromine salt (309): take 9-acetyl group-B-carboline and cylite as raw material, get yellow trichite, yield 67%, m.p.212-214 ℃; IR (KBr) ν: 1650-3050,1630.6,1581.4,1493.9,1448.9,1345.3,1291.4,1260.5,1235.1,1195.5,1152.0,123.5,1082.2,1031.4,1012.8,877.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.07 (1H, s, H-1); (9.13-9.15 1H, d, H-3); (8.96-8.98 1H, d, H-8); (8.59-8.61 1H, d, H-4); (8.29-8.31 1H, d, H-5); (7.94-7.98 1H, t, H-6); (7.67-7.69 1H, t, H-7); (7.55-7.57 2H, d, Ph-H); (7.41-7.49 4H, m, Ph-H); 6.09 (2H, m, NCH ₂Ph); 3.00 (3H, s, NCOCH ₃).

2,9-two (2,3,4,5,6-PFBBR)-B-carboline bromine salt (310): be raw material with 9-(2,3,4,5,6-, five fluorine) benzyl-B-carboline and 2,3,4,5,6-, five fluorine cylites, get light yellow crystal, yield 81.3%, m.p.209-211 ℃; MS m/e 529; IR (KBr) ν: 1650-3050,1641.5,1530.5,1502.4,1453.9,1426.9,1348.9,1149.4,1129.7,1033.2,773.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 11.69 (1H, d, H-4); (8.39-8.40 1H, d, H-1); (8.22-8.28 2H, m, H-8, H-3); (7.83-7.87 1H, t, H-5); (7.63-7.65 1H, d, H-6); (7.51-7.55 1H, t, H-7); 6.51-6.31 (4H, m, NCH ₂C ₆F ₅).

2-benzyl-9-phenylpropyl-B-carboline bromine salt (311): take 9-phenylpropyl-B-carboline and cylite as raw material, obtain yellow crystals, yield 46%, m.p.201-203 ℃; MS m/e 286; IR (KBr) ν: 1650-3100,1637.7,1607.6,1510.4,1456.2,1396.8,1341.2,1270.9,1247.3,1210.1,1143.2,1069.8,844.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.91 (1H, s, H-4); (8.82 2H, s, H-1, H-8); (8.51-8.53 1H, d, H-3); (7.87-7.96 2H, m, H-5, H-6); (7.59-7.61 2H, d, H-7, PhH); (7.43-7.51 4H, m, PhH); (7.03-7.15 5H, m, PhH); 5.96 (2H, s, NCH ₂Ph); 4.70-4.74 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.64-2.66 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.20-2.21 (2H, m, NCH ₂CH ₂CH ₂Ph).

2-(3-chlorobenzyl)-9-phenylpropyl-B-carboline bromine salt (312): take 9-phenylpropyl-B-carboline and 3-chlorine cylite as raw material, obtain yellow crystals, yield 70.4%, m.p.194-195 ℃; MS m/e 286; IR (KBr) ν: 1650-3050,1639.4,1601.0,1574.9,1511.7,1470.7,1336.7,1182.2,1143.6,1075.7,797.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.99 (1H, s, H-4); (8.83 2H, s, H-1, H-8); (8.52-8.54 1H, d, H-3); (7.87-7.97 2H, m, H-5, H-6); (7.79 1H, s, H-7); (7.60-7.62 1H, m, PhH); (7.50-7.52 3H, m, PhH); (7.05-7.16 5H, m, PhH); 5.99 (2H, s, NCH ₂Ph); 4.72-4.75 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.66-2.70 (2H, t, NCH ₂CH ₂CH ₂Ph) .2.21-2.24 (2H, m, NCH ₂CH ₂CH ₂Ph).

2-(4-luorobenzyl)-9-phenylpropyl-B-carboline bromine salt (313): take 9-phenylpropyl-B-carboline and 4-fluorine cylite as raw material, obtain yellow crystals, yield 79.2%, m.p.194-195 ℃; MS m/e 287; IR (KBr) ν: 1650-3100,1637.8,1606.4,1574.1,1511.0,1456.8,1340.5,1271.4,1227.4,1178.3,1143.3,1070.8,831.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.91 (1H, s, H-4); (8.83 2H, s, H-8, H-1); (8.52-8.54 1H, d, H-3); (7.88-7.97 2H, m, H-5, H-6); (7.70-7.73 2H, m, H-7, PhH); (7.51-7.54 1H, m, PhH); (7.29-7.34 1H, m, PhH); (7.05-7.17 5H, m, PhH); 5.96 (2H, s, NCH ₂Ph); 4.71-4.74 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.66-2.69 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.21-2.24 (2H, m, NCH ₂CH ₂CH ₂Ph).

9-(3-chlorobenzyl)-2-(4-luorobenzyl)-B-carboline bromine salt (314): take 9-(3-chlorine) benzyl-B-carboline and 4-fluorine cylite as raw material, pale yellow crystals, yield 77%, m.p.256-258 ℃; MS m/e 292; IR (KBr) ν: 1650-3050,1641.1,1604.5,1575.4,1509.7,1461.5,1394.5,1343.6,1290.9,1266.8,1221.7,1157.5,1137.1,1100.5,1062.5,917.7,895.1,857.4,822.4,747.5cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.50 (1H, s, H-4); (8.92-8.93 2H, m, H-8, H-1); (8.57-8.59 1H, d, H-3); (7.94-7.96 1H, d, H-5); (7.86-7.90 1H, m, H-6); (7.69-7.72 2H, m, H-7, PhH); (7.52-7.56 1H, m, PhH); (7.45 1H, s, PhH); (7.21-7.39 5H, m, PhH); 5.95-5.98 (4H, d, NCH ₂Ph).

2,9-two (3-chlorobenzyl)-B-carboline bromine salt (315): take 9-(3-chlorine) benzyl-B-carboline and 3-chlorine cylite as raw material, pale yellow crystals, yield 74%, m.p.262-264 ℃; MS m/e 292; IR (KBr) ν: 1650-3050,1639.2,1698.3,1575.6,1509.8,1468.8,1433.2,1393.1,1335.1,1284.8,1266.0,1211.0,1175.9,1139.4,1082.3,1061.8,923.2,864.7,794.2,747.1cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.08 (1H, s, H-4); (8.95-8.96 2H, m, H-8, H-1); (8.58-8.60 1H, m, H-3); (7.94-7.96 1H, d, H-5); (7.86-7.90 1H, t, H-6); (7.75-7.75 1H, s, H-7); (7.45-7.59 5H, m, PhH); (7.33-7.39 2H, m, PhH); (7.23-7.25 1H, m, PhH); 5.96-6.01 (4H, d, NCH ₂Ph).

9-(3 chlorobenzyl)-2-benzyl-B-carboline bromine salt (316): take 9-(3-chlorine) benzyl-B-carboline and cylite as raw material, pale yellow crystals, yield 70%, m.p.267-269 ℃; MS m/e 292; IR (KBr) ν: 1650-3050,1639.7,1603.6,1576.3,1510.7,1460.1,1433.7,1394.8,1341.7,1288.1,1266.8,1210.2,1174.2,1106.0,1081.5,1061.8,932.4,891.2,816.4,771.0,749.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.08 (1H, s, H-4); (8.95-8.95 2H, m, H-8, H-1); (8.57-8.59 1H, m, H-3); (7.94-7.97 1H, d, H-5); (7.86-7.90 1H, t, H-6); (7.57-7.60 2H, m, H-7, PhH); (7.51-7.55 1H, t, PhH); (7.41-7.46 4H, m, PhH); (7.32-7.39 2H, m, PhH); (7.20-7.22 1H, d, PhH); 5.95-5.98 (4H, m, NCH ₂Ph).

9-butyl-2-benzyl-B-carboline bromine salt (317): take 9-butyl-B-carboline and cylite as raw material, get yellow crystals, yield 81.2%, m.p.228-230 ℃; MS m/e 395; IR (KBr) ν: 1650-3050,1639.3,1608.4,1572.5,1511.0,1458.0,1336.5,1268.9,1244.8,1218.4,1175.3,1148.2,1072.3,912.3,815.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.11 (1H, s, H-4); (8.87 2H, s, H-8, H-1); (8.52-8.50 1H, d, H-3); (7.86-7.95 1H, d, H-5); (7.85-7.83 1H, t, H-6); (7.65-7.62 2H, d, H-7, PhH); (7.48-7.40 4H, m, PhH); 6.02 (2H, s, NCH ₂Ph); 4.66-4.63 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.84-1.80 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.32-1.27 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.88-0.85 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

9-octyl group-2-benzyl-B-carboline bromine salt (318): take 9-octyl group-B-carboline and cylite as raw material, get yellow crystals, yield 76.5%, m.p.195-195 ℃; MS m/e 451; IR (KBr) ν: 1650-3050,1639.3,1609.1,1572.6,1511.1,1460.5,1395.7,1336.2,1258.6,1234.6,1208.9,1178.8,1143.9,1069.7,853.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 10.07 (1H, s, H-4); (8.88 2H, s, H-8, H-1); (8.54-8.52 1H, d, H-3); (7.97-7.95 1H, d, H-5); (7.88-7.85 1H, t, H-6); (7.63-7.60 2H, d, H-7, PhH); (7.51-7.38 4H, m, PhH); 6.00 (2H, s, NCH ₂Ph); 4.66-4.63 (2H, m, NCH ₂C ₇H ₁₅); 1.84-1.82 (2H, m, NCH ₂CH ₂C ₆H ₁₃); 1.23-1.14 (10H, m, NCH ₂CH ₂C ₅H ₁₀CH ₃); 0.81-0.77 (3H, m, NC ₇H ₁₄CH ₃).

2-(4-luorobenzyl)-9-ethyl-B-carboline bromine salt (319): take 9-ethyl-B-carboline and 4-fluorine cylite as raw material, obtain yellow crystals, yield 64%, m.p.174-175 ℃; MS m/e 196; IR (KBr) ν: 1650-3100,1639.9,1606.3,1573.8,1512.0,1466.7,1453.9,1362.0,1337.4,1293.4,1222.6,1125.3,1066.5,865.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.96 (1H, s, H-4); (8.81-8.87 2H, t, H-8, H-1); (8.54-8.56 1H, d, H-3); (7.98-8.00 1H, d, H-5); (7.88-7.92 1H, t, H-6); (7.69-7.72 2H, m, H-7, PhH); (7.50-7.54 1H, t, PhH); (7.28-7.33 2H, t, PhH); 5.93 (2H, s, NCH ₂Ph-H); 4.67-4.69 (2H, t, NCH ₂CH ₃); 1.43-1.46 (3H, m, NCH ₂CH ₃).

2-benzyl-9-ethyl-B-carboline bromine salt (320): take 9-ethyl-B-carboline and cylite as raw material, obtain yellow crystals, yield 66.2%, m.p.〉250 ℃; MS m/e 196; IR (KBr) ν: 1650-3100,1639.0,1561.3,1512.2,1462.5,1336.4,1245.7,1210.9,1178.4,1147.7,772.4cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.98 (1H, s, H-4); (8.82-8.87 2H, t, H-8, H-1); (8.53-8.55 1H, d, H-3); (7.97-7.99 1H, d, H-5); (7.87-7.90 1H, t, H-6); (7.59-7.62 2H, d, H-7, PhH); (7.40-7.53 4H, m, PhH); 5.97 (2H, s, NCH ₂Ph); 4.69-4.71 (2H, m, NCH ₂CH ₃); 1.42-1.45 (3H, t, NCH ₂CH ₃).

2-pi-allyl-9-benzyl-B-carboline bromine salt (321): take 9-benzyl-B-carboline and bromopropene as raw material, obtain yellow little red crystal, m.p.123-124 ℃; MS m/e 258; IR (KBr) ν: 1650-3100,1637.9,1611.9,1577.5,1509.5,1468.3,1455.6,1394.7,1340.1,1276.8,1216.1,1173.9,1150.7,1134.4,1056.9,821.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.98 (1H, s, H-4); (8.82-8.87 2H, t, H-8, H-1); (8.53-8.55 1H, d, H-3); (7.97-7.99 1H, d, H-5); (7.87-7.90 1H, t, H-6); (7.59-7.62 2H, d, H-7, PhH); (7.40-7.53 4H, m, PhH); 5.97 (2H, s, NCH ₂Ph); 4.69-4.71 (2H, m, NCH ₂CH ₃); 1.42-1.45 (3H, t, NCH ₂CH ₃).

2-PFBBR-9-ethyl-B-carboline bromine salt (322): be raw material with 9-ethyl-B-carboline and 2,3,4,5,6-, five fluorine cylites, obtain yellow crystals, yield 75.3%, m.p.〉250 ℃; MS m/e 377; IR (KBr) ν: 1650-3100,1642.8,1613.4,1507.9,1477.4,14545,1336.2,1245.4,1157.2,1130.7,1063.4,1041.4,9559.0,927.3,768.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.76 (1H, s, H-4); (8.87-8.89 1H, d, H-1); (8.71-8.72 1H, d, H-8); (8.57-8.59 1H, d, H-3); (8.99-8.01 1H, d, H-5); (7.90-7.94 1H, t, H-6); (7.52-7.56 1H, t, H-7); 6.21 (2H, s, NCH ₂Ph); 4.67-4.73 (2H, m, NCH ₂CH ₃); 1.41-1.44 (3H, t, NCH ₂CH ₃).

(the raw material 9-ethyl-B-carboline of this chemical compound former document in open)

Embodiment B-4:

The general synthesis technique (323-327) of 1-methyl-9-replacement-beta-carboline alkaloid derivant:

Get 1-methyl-B-carboline (10mmol) and place the 200ml round-bottomed flask, add drying tube on the flask, add 60ml N, dinethylformamide, magnetic agitation treats that dissolving is placed in the ice-water bath, adds sodium hydride (16mmol), magnetic agitation simultaneously, question response liquid cooling are but and stir evenly rear adding alkyl halide (12mmol).TLC monitoring reaction process (every the 10min monitoring).(general response time 30min) pours reactant liquor in the 50ml water into after the raw material complete reaction, is extracted in the water with ethyl acetate (400ml, minute four extractions) to have (with the TLC monitoring, existing without product point onboard) without product.Organic facies with the washing of 200ml washing twice, 100ml saturated sodium-chloride once added anhydrous sodium sulfate drying 5 hours, the filtering desiccant is concentrated into extract dried, adds the 40ml dehydrated alcohol, it is an amount of to add concentrated hydrochloric acid, and solid is dissolved fully, transfers pH2-3, be concentrated into a small amount of liquid of residue, add a small amount of acetone, cold preservation is more than 10 hours, filter, solid washes twice with petroleum ether, and solid is poured in the 50ml water, adds sodium bicarbonate and transfers pH about 8, divide four extractions with the 200ml ethyl acetate, organic addition anhydrous sodium sulfate drying adds activated carbon decolorizing, leaves standstill about 5 hours, cross silica gel G, use the ethyl acetate rinse silica gel G, the liquid under waiting to filter exists without product, stops flushing, filtrate is concentrated into dried, add the petroleum ether recrystallization, cold preservation was treated crystallization about 10 hours, filtered, wash with petroleum ether, obtain chemical compound (I), drying gets product.

1-methyl-9-ethyl-B-carboline (323): take 1-methyl-B-carboline and bromoethane as raw material, get white crystal, yield 78.3%, m.p.116.4-117.8 ℃; MS m/e 210; IR (KBr) ν: 1650-3050,1635.2,1574.8,1530.2,1555.2,1384.2,1301.1,1334.3,1256.7,1133.3,863.7,851.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.84 (1H, s, H-4); (8.07 1H, s, H-8); (7.98-8.02 1H, d, H-5); (7.91-7.93 1H, d, H-3); (7.66-7.68 1H, m, H-6); (7.47-7.49 1H, m, H-7); 4.68-4.71 (2H, m, NCH ₂CH ₃); 1.46-1.49 (3H, t, NCH ₂CH ₃).

1-methyl-9-hexyl-B-carboline (324): take 1-methyl-B-carboline and iodo normal hexane as raw material, get yellow powder, yield 71.3%, m.p.62.3-63.6 ℃; MS m/e 266; IR (KBr) ν: 1650-3100,1620.1-1562.1,1475.8,1446.7,1405.5,1361.6,1288.6,1229.4,1191.1,1167,1135.3,1093.9,971.6,776.0,729.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.33-8.34 (1H, d, H-4); (8.12-8.14 1H, m, H-8); (7.85-7.86 1H, m, H-3); (7.57-7.61 1H, m, H-5); (7.46-7.48 1H, m, H-6); (7.26-7.30 1H, m, H-7); 4.51-4.55 (2H, t, NCH ₂(CH ₂) ₄CH ₃); 3.06 (3H, s, CH ₃); 1.81-1.88 (2H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 1.41-1.48 (2H, m, NCH ₂CH ₂CH ₂(CH ₂) ₂CH ₃); 1.28-1.38 (4H, m, NCH ₂(CH ₂) ₂CH ₂CH ₂CH ₃); 0.86-0.91 (3H, m, N (CH ₂) ₅CH ₃).

1-methyl-9-octyl group-B-carboline (325): take 1-methyl-B-carboline and iodo normal octane as raw material, get the light brown solid, yield 26.5%, m.p.29-31 ℃; MS m/e 296; IR (KBr) ν: 1650-3100,1620.5-1562.7,1474.8,1453.0,1444.4,1405.7,1358.7,1332.4,1250.9,1218.6,1183.0,1135.2,1116.8,1049.3,1018.2,971.4,822.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.33-8.34 (1H, d, H-4); (8.11-8.14 1H, d, H-8); (7.84-7.86 1H, d, H-3); (7.57-7.61 1H, m, H-5); (7.45-7.47 1H, d, H-6); (7.26-7.30 1H, t, H-7); 4.50-4.54 (2H, t, NCH ₂(CH ₂) ₆CH ₃); 3.06 (3H, s, CH ₃); 1.80-1.88 (2H, m, NCH ₂CH ₂(CH ₂) ₅CH ₃); 1.43-1.47 (2H, m, NCH ₂CH ₂CH ₂(CH ₂) ₄CH ₃); 1.26-1.41 (8H, m, NCH ₂CH ₂CH ₂(CH ₂) ₄CH ₃); 0.85-0.93 (3H, m, NCH ₂(CH ₂) ₆CH ₃).

1-methyl-9-benzyl-B-carboline (326): take 1-methyl-B-carboline and cylite as raw material, get white crystal, yield 86.4%; M.p.182.4-184.2 ℃; MS m/e 272; IR (KBr) ν: 1650-3050,1624.1,1574.7,1514.7,1493.5,1463.2,1452.4,1382.4,1337.0,1318.5,1245.3,1215.0,1137.4,10761.0,1028.8,840.3,798.1,761.8cm ^-1; ¹H-NMR (CDCl ₃) δ 8.93-8.95 (1H, d, H-4); (8.45-8.47 1H, d, H-8); (8.30-8.37 1H, m, H-3); (7.74-7.78 1H, m, H-5); (7.46-7.53 2H, m, H-6, H-7); (7.30-7.38 3H, m, PhH); (7.09-7.11 2H, t, PhH); 6.00 (2H, s, NCH ₂Ph); 4.86-4.90 (2H, t, CH ₂CH ₂CH ₂CH ₃); 3.22 (3H, s, CH ₃); 1.89-1.93 (2H, m, CH ₂CH ₂CH ₂CH ₃); 1.46-1.52 (2H, m, CH ₂CH ₂CH ₂CH ₃); 0.94-0.98 (3H, t, C ₃H ₆CH ₃).

1-methyl-9-[(2,3,4,5,6-, five fluorine) benzyl]-B-carboline (327): be raw material with 1-methyl-B-carboline and 2,3,4,5,6-, five fluorine cylites, get white crystal, yield 90.2%, m.p.221-223 ℃; MS m/e362; IR (KBr) ν: 1650-3080,1626.9,1575.4,1530.2,1464.4,1363.7,1171.1,1145.4,1120.4,1010.2,978.5,940.4,839.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.91-8.93 (1H, d, H-4); (8.56-8.58 1H, d, H-8); (8.32-8.34 1H, d, H-3); (7.88-7.91 1H, m, H-5); (7.49-7.56 2H, m, H-6, H-7); 5.88 (2H, s, NCH ₂Ph); 3.12 (3H, s, CH ₃).

Embodiment B-5:

1-methyl-2,9-two replaces the general synthesis technique (328-340) of beta-carboline alkaloid derivant:

Take by weighing 1-methyl-9-and replace B-carboline (10mmol), add the 50ml ethyl acetate it is dissolved fully, add corresponding halogenated alkane (20-50mmol), reflux 8-20 hour, be cooled to room temperature, the solid that filtration is separated out, a small amount of ethyl acetate washing is dissolved in solid in the dehydrated alcohol subsequently, reflux is to clarification, filtered while hot is placed the refrigerator recrystallization, gets white or pale yellow crystals.

1-methyl-9-benzyl-2-ethyl-B-carboline bromine salt (328): take 1-methyl-9-benzyl-B-carboline and bromoethane as raw material, get buff powder, yield 79%, m.p.〉270 ℃; MS m/e 272; IR (KBr) ν: 1650-3100,1627.0,1577.6,1514.6,1495.0,1464.4,1339.8,1318.0,1252.5,1216.2,1163.4,1137.5,1071.6,1029.2,774.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.79-8.83 (2H, m, H-4, H-8); (8.57-8.59 1H, d, H-3); (7.83-7.88 2H, m, H-5, H-6); (7.51-7.55 1H, m, H-7); (7.30-7.37 3H, m, PhH); (7.07-7.09 2H, d, PhH); 6.08 (2H, t, PhCH ₂); 4.73-4.78 (2H, m, NCH ₂CH ₃); 3.07 (3H, s, CH ₃); 1.47-1.59 (3H, t, NCH ₂CH ₃).

1-methyl-9-benzyl-2-butyl-B-carboline iodine salt (329): take 1-methyl-9-benzyl-B-carboline and iodo-n-butane as raw material, get yellow crystals, yield 81.2%; M.p.244.6-246.6 ℃; MS m/e 272; IR (KBr) ν: 1650-3050,1624.1,1574.7,1514.7,1493.5,1463.2,1452.4,1382.4,1337.0,1318.5,1245.3,1215.0,1137.4,10761.0,1028.8,840.3,798.1,776.0,761.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.93-8.95 (1H, d, H-4); (8.45-8.47 1H, d, H-8); (8.30-8.37 1H, m, H-3); (7.74-7.78 1H, m, H-5); (7.46-7.53 2H, m, H-6, H-7); (7.30-7.38 3H, m, PhH); (7.09-7.11 2H, t, PhH); 6.00 (2H, s, NCH ₂Ph); 4.86-4.90 (2H, t, CH ₂CH ₂CH ₂CH ₃); 3.22 (3H, s, CH ₃); 1.89-1.93 (2H, m, CH ₂CH ₂CH ₂CH ₃); 1.46-1.52 (2H, m, CH ₂CH ₂CH ₂CH ₃); 0.94-0.98 (3H, t, C ₃H ₆CH ₃).

1-methyl-9-benzyl-2-hexyl-B-carboline iodine salt (330): take 1-methyl-9-benzyl-B-carboline and iodo normal hexane as raw material, get yellow crystals, yield 87%, m.p.198.7-199.0 ℃; MS m/e 356; IR (KBr) ν: 1650-3100,1622.9,1574.0,1513.1,1491.7,1452.7,1334.6,1317.9,1242.6,1213.6,1155.7,1133.5,1075.5,1029.7,779.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.79-8.81 (1H, d, H-4); (8.43-8.45 1H, d, H-8); (8.29-8.31 1H, d, H-3); (7.75-7.78 1H, t, H-5); (7.46-7.53 2H, m, H-6, H-7); (7.30-7.38 3H, m, PhH); (7.10-7.11 2H, d, PhH); 5.99 (2H, s, NCH ₂Ph); 4.78-4.80 (2H, t, NCH ₂C ₅H ₁₁); 3.22 (3H, s, CH ₃); 1.93 (2H, m, NCH ₂CH ₂C ₄H ₉); 1.44 (2H, m, NCH ₂CH ₂CH ₂C ₃H ₇); 1.29-1.30 (4H, m, NC ₃H ₆CH ₂CH ₂CH ₃); 0.83-0.87 (3H, t, NC ₅H ₁₀CH ₃).

1-methyl-2,9-dibenzyl-B-carboline bromine salt (331): take 1-methyl-9-benzyl-B-carboline and cylite as raw material, get yellow powder shape crystal, yield 92%, m.p〉270 ℃; MS m/e 363; IR (KBr) ν: 1650-3050,1623.0,1572.4,1507.3,1493.1,1452.8,1387.3,1364.3,1335.6,1320.6,1247.7,1222.4,1175.7,1147.4,1132.6,1078.4,1026.0,853.6cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.95-9.00 (2H, m, H-4, H-8); (8.65-8.67 1H, d, H-3); (7.88-7.97 2H, m, H-5, H-6); (7.57-7.61 1H, m, H-7); (7.29-7.45 6H, m, PhH); (7.18-7.20 2H, t, PhH); (7.04-7.06 2H, d, PhH); 6.09-6.10 (4H, d, NCH ₂Ph); 2.96 (3H, s, CH ₃).

1-methyl-9-benzyl-2-[(2,3,4,5,6-five fluorine) benzyl]-B-carboline bromine salt (332): with 1-methyl-9-benzyl-B-carboline and 2,3,4,5,6-five fluorine cylites are raw material, get yellow powder shape crystal, yield 84%, m.p.237.7-238.5 ℃; MS m/e 273; IR (KBr) ν: 1650-3100,1626.8,1577.4,1523.3,1499.4,1465.3,1450.7,1422.7,379.8,1359.7,1335.6,1319.7,1248.6,1214.4,1151.6,1121.4,1046.0,1013.5,964.6,947.9,855.7,807.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.99-9.01 (1H, d, H-4); (8.89-8.91 1H, d, H-8); (8.59-8.61 1H, d, H-3); (7.87-7.94 2H, m, H-5, H-6); (7.54-7.58 1H, m, H-7); (7.38-7.44 3H, m, PhH); (7.18-7.20 2H, t, PhH); 6.22 (2H, s, NCH ₂Ph); 6.10 (2H, s, NCH ₂Ph); 3.06 (3H, s, CH ₃).

1-methyl-9-ethyl-2-butyl-B-carboline iodine salt (333): take 1-methyl-9-ethyl-B-carboline and iodo-n-butane as raw material, yellow powder powder crystal, yield 86.4%, m.p.169-171 ℃; MS m/e 267; IR (KBr) ν: 1650-3100,1625.9,1574.7,1518.0,1495.2,1461.4,1383.9,1338.2,1317.7,1235.2,1136.2-900.0,867.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.72-8.76 (2H, m, H-4, H-8); (8.51-8.53 1H, d, H-3); (7.97-7.99 1H, d, H-5); (7.84-7.89 1H, m, H-6); (7.48-7.52 1H, m, H-7); 4.75-4.83 (4H, m, NCH ₂CH ₃, NCH ₂CH ₂CH ₂CH ₃); 3.52 (3H, s, CH ₃); 1.87-1.91 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.41-1.47 (5H, m, NCH ₂CH ₃, NCH ₂CH ₂CH ₂CH ₃); 0.95-0.99 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-9-ethyl-2-benzyl-B-carboline bromine salt (334): take 1-methyl-9-ethyl-B-carboline and cylite as raw material, get yellow powder shape crystal, yield 88%, m.p.241.1-243.6 ℃; MS m/e 302; IR (KBr) ν: 1650-3050,1623.2,1573.4,1515.8,1494.7,1457.4,1382.8,1338.6,1314.3,1233.1,1206.2,1156.8,1137.2,1111.4,1078.8,1062.8,1030.2,945.0,863.0,817.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.92-8.94 (1H, d, H-4); (8.41-8.43 1H, d, H-8); (8.27-8.29 1H, t, H-3); (7.81-7.85 1H, m, H-5); (7.60-7.62 1H, d, H-6); (7.46-7.50 1H, m, H-7); (7.28-7.38 3H, m, PhH); (7.22-7.25 2H, m, PhH); 6.42 (2H, s, NCH ₂PhH); 4.67-4.72 (2H, m, NCH ₂CH ₃); 3.41 (3H, s, CH ₃); 1.57-1.59 (3H, t, NCH ₂CH ₃).

1-methyl-9-ethyl-2-[(2,3,4,5,6-five fluorine) benzyl]-B-carboline bromine salt (335): with 1-methyl-9-ethyl-B-carboline and 2,3,4,5,6-five fluorine cylites are raw material, obtain yellow powder shape crystal, yield 77.3%, m.p.221-222 ℃; MS m/e 210; IR (KBr) ν: 1650-3100,1625.3,1576.0,1523.3,1498.6,1459.6,1385.0,1335.0,1317.4,1233.1,1137.6,1119.3,1080.1,1013.2,981.4,943.2,851.0,826.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.90-8.91 (1H, d, H-4); (8.78-8.80 1H, d, H-8); (8.55-8.57 1H, d, H-3); (7.98-8.01 1H, d, H-5); (7.88-7.92 1H, t, H-6); (7.51-7.55 1H, t, H-7); 6.29 (2H, s, NCH ₂Ph); 4.75-4.80 (2H, m, NCH ₂CH ₃); 3.22 (3H, s, CH ₃); 1.44-1.47 (3H, t, NCH ₂CH ₃).

1-methyl-2,9-diethyl-B-carboline bromine salt (336): take 1-methyl-9-ethyl-B-carboline and bromoethane as raw material, get pale yellow powder shape crystal, yield 90.5%, m.p.177.4-179.3 ℃; MS m/e 239; IR (KBr) ν: 1650-3100,1634.5,1575.5,1528.3,1504.0,1451.7,1384.2,1300.9,1335.1,1257.7,1228.1,1133.5,863.3,850.6,808.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.04 (2H, s, H-4, H-8); (7.98-8.02 2H, m, H-5, H-3); (7.62-7.66 1H, t, H-6); (7.30-7.33 1H, t, H-7); 4.62-4.66 (2H, m, NCH ₂CH ₃); 3.36 (3H, s, CH ₃); 1.85-1.93 (2H, m, NCH ₂CH ₃); 1.44-1.49 (3H, t, NCH ₂CH ₃); 0.98-1.02 (3H, t, NCH ₂CH ₃).

1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-2-ethyl-B-carboline bromine salt (337): with 1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-B-carboline and bromoethane are raw material, off-white powder shape crystal, yield 60.2%, m.p.246-248 ℃; MS m/e 362; IR (KBr) ν: 1650-3100,1627.8,1579.2,1528.5,1503.1,1462.1,1362.4,1170.2,1145.4,1120.4,1010.2,978.5,940.4,839.0cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.89-8.87 (1H, d, H-4); (8.41-8.42 1H, d, H-8); (8.25-8.27 1H, d, H-3); (7.77-7.81 1H, m, H-5); (7.47-7.52 2H, m, H-6, H-7); 6.16 (2H, s, NCH ₂Ph); 4.99-5.05 (2H, m, NCH ₂CH ₃); 3.52 (3H, s, CH ₃); 1.71-1.74 (3H, t, NCH ₂CH ₃).

1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-2-butyl-B-carboline iodine salt (338): with 1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-B-carboline and iodo-n-butane are raw material, get yellow powder shape crystal, yield 88.2%, m.p.237-239 ℃; MS m/e 362; IR (KBr) ν: 1650-3100,1464.6,1421.8,1360.3,1341.1,1318.6,1246.0,1219.2,1145.1,1116.1,1080.7,1012.7,980.5,938.3,762.7,734.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.92-8.93 (1H, d, H-4); (8.40-8.41 1H, d, H-8); (8.25-8.27 1H, d, H-3); (7.75-7.79 1H, m, H-5); (7.45-7.51 2H, m, H-6, H-7); 6.18 (2H, s, NCH ₂Ph); 4.96-4.99 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.53 (3H, s, CH ₃); 1.98-2.01 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.65-1.68 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.99-1.03 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-2-benzyl-B-carboline bromine salt (339): with 1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-B-carboline and cylite are raw material, get yellow powder powder crystal, yield 76%, m.p.263-265 ℃; MS m/e 362; IR (KBr) ν: 1650-3100,1503.4-1623.0,1454.3,1390.5,1364.2,1312.8,1245.0,1017.0-1217.8,958.3,943.7,846.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.99-9.00 (1H, d, H-4); 8.89-8.90 (1H, d, H-8); (8.58-8.60 1H, d, H-3); (7.89-7.93 2H, m, H-5, H-6); (7.54-7.58 1H, m, H-7); (7.38-7.44 3H, m, PhH); (7.18-7.20 2H, m, PhH); 6.22 (2H, s, NCH ₂Ph); 6.10 (2H, s, NCH ₂Ph); 3.05 (3H, s, CH ₃).

1-methyl-2,9-two [(2,3,4,5,6-, five fluorine) benzyl]-B-carboline bromine salt (340): with 1-methyl-9-[(2,3,4,5,6-five fluorine) benzyl]-B-carboline and 2,3,4,5,6-, five fluorine cylites are raw material, get yellow powder powder crystal, yield 90.8%, m.p.225-227 ℃; MS m/e 362; IR (KBr) ν: 1650-3100,1626.0,1581.1,1527.1,1499.1,1464.3,1375.4,1253.8,1218.0,1125.4,1009.8,966.2,937.0,771.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.93-8.95 (1H, d, H-4); (8.82-8.84 1H, d, H-8); (8.57-8.59 1H, d, H-3); (7.91 2H, m, H-5, H-6); (7.54-7.57 1H, m, H-7); 6.27 (2H, s, NCH ₂Ph); 6.20 (2H, s, NCH ₂Ph); 3.11 (3H, s, CH ₃).

Embodiment B-6:

1,9-two replaces the general synthesis technique (341-366) of beta-carboline alkaloid derivant:

Get 1-replacement-B-carboline (10mmol) and place the 200ml round-bottomed flask, add drying tube on the flask, add 60mlN, dinethylformamide, magnetic agitation treats that dissolving is placed in the ice-water bath, adds sodium hydride (16mmol), magnetic agitation simultaneously, question response liquid cooling are but and stir evenly rear adding alkyl halide (12mmol).TLC monitoring reaction process (every the 10min monitoring).(general response time 30min) pours reactant liquor in the 50ml water into after the raw material complete reaction, is extracted in the water with ethyl acetate (400ml, minute four extractions) to have (with the TLC monitoring, existing without product point onboard) without product.Organic facies with the washing of 200ml washing twice, 100ml saturated sodium-chloride once added anhydrous sodium sulfate drying 5 hours, the filtering desiccant is concentrated into extract dried, adds the 40ml dehydrated alcohol, it is an amount of to add concentrated hydrochloric acid, and solid is dissolved fully, transfers pH2-3, be concentrated into a small amount of liquid of residue, add a small amount of acetone, cold preservation is more than 10 hours, filter, solid washes twice with petroleum ether, and solid is poured in the 50ml water, add sodium bicarbonate and transfer pH about 8, divide four extractions, organic addition anhydrous sodium sulfate drying with the 200ml ethyl acetate, add activated carbon decolorizing, leave standstill about 5 hours, cross silica gel G, use the ethyl acetate rinse silica gel G, liquid under waiting to filter exists without product, stops flushing, filtrate is concentrated into dried, add the petroleum ether recrystallization, cold preservation was treated crystallization about 10 hours, filtered, and washed with petroleum ether, drying gets product.

9-ethyl-1-benzyl-B-carboline (341): take 1-benzyl-B-carboline and bromoethane as raw material, get light yellow granular crystal, yield 62.8%, m.p.148-149 ℃; MS m/e 287; IR (KBr) ν: 1650-3100,1619.0,1557.3,1490.5,1476.8,1451.5,1424.9,1383.3,1366.2,1334.7,1313.2,1227.8,1189.8,1158.5,1108.5,1077.9,1046.5,830.3,811.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.46-8.47 (1H, d, H-4); (8.14-8.17 1H, m, H-3); (7.94-7.96 1H, d, H-8); (7.55-7.60 1H, m, H-5); (7.40-7.42 1H, d, H-6); (7.27-7.30 1H, m, H-7); (7.10-7.25 5H, m, PhH); 4.73 (2H, s, CH ₂Ph); 4.37-4.42 (2H, m, NCH ₂CH ₃); 1.21-1.30 (3H, t, NCH ₂CH ₃).

9-butyl-1-benzyl-B-carboline (342): take 1-benzyl-B-carboline and iodo-n-butane as raw material, get yellow granular crystal, yield 83.0%, m.p.72-73 ℃; MS m/e 315; IR (KBr) ν: 1650-3100,1619.8,1558.1,1489.7,1477.2,1450.6,1425.3,1365.0,1328.8,1265.8,1233.3,1148.3,1128.8,1106.6,1045.1,843.9,822.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.46-8.48 (1H, d, H-4); (8.14-8.15 1H, d, H-3); (7.94-7.95 1H, d, H-8); (7.54-7.58 1H, m, H-5); (7.38-7.40 1H, d, H-6); (7.27-7.29 1H, m, H-7); (7.23-7.26 2H, m, PhH); (7.08-7.19 3H, m, PhH); 4.73 (2H, s NCH ₂Ph); 4.27-4.31 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.62-1.68 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.32-1.37 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.89-0.93 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-hexyl-1-benzyl-B-carboline (343): take 1-benzyl-B-carboline and iodo normal hexane as raw material, get yellow granular crystal, yield 73.2%, m.p.46-47 ℃; MS m/e 341; IR (KBr) ν: 1650-3100,1620.5,1559.6,494.0,471.1,1450.2,1414.5,1359.1,1330.5,1229.9,1181.1,1156.4,1130.8,1047.6,829.6,815.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.47-8.48 (1H, d, H-4); (8.15-8.17 1H, d, H-3); (7.96-7.97 1H, d, H-8); (7.56-7.60 1H, t, H-5); (7.39-7.41 1H, d, H-6); (7.08-7.31 6H, m, H-7, PhH); 4.74 (2H, s, NCH ₂Ph); 4.27-4.31 (2H, t, NCH ₂(CH ₂) ₄CH ₃); 1.62-1.68 (2H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 1.27-1.34 (6H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 0.89-0.93 (3H, t, NCH ₂(CH ₂) ₄CH ₃).

1,9-dibenzyl-B-carboline (344): take 1-benzyl-B-carboline and cylite as raw material, get yellow column crystal, yield 81.7%, m.p.155-156 ℃; MS m/e 348; IR (KBr) ν: 1650-3100,1620.0,1560.2,1491.6,1452.12,1428.2,1359.1,1331.6,1309.2,1245.0,1207.2,1157.4,1135.0,1108.8,1077.7,1045.9,831.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.51-8.53 (1H, d, H-4); (8.20-8.22 1H, d, H-3); (8.02-8.03 1H, d, H-8); (7.52-7.56 1H, m, H-5); (7.38-7.40 1H, d, H-6); (7.27-7.34 4H, m, H-7, PhH); (7.17-7.26 2H, m, PhH); (7.03-7.04 2H, d, PhH); (6.92-6.94 2H, d, PhH); 5.50 (2H, s, CH ₂Ph); 4.46 (2H, s, NCH ₂Ph).

1-benzyl-9-(4-luorobenzyl)-B-carboline (345): take 1-benzyl-B-carboline and 4-fluorine cylite as raw material, get white trichite, yield 74.5%, m.p.177-179 ℃; MS m/e 458; IR (KBr) ν: 1650-3100,1619.6,1603.2,1559.6,1508.5,1478.1,1453.2,1427.9,1359.5,1310.5,1224.1,1155.2,1129.4,1090.5,1047.3,1029.8,836.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.53 (1H, d, H-4); (8.22-8.24 1H, d, H-3); (8.08-8.09 1H, d, H-8); (7.56-7.59 1H, t, H-5); (7.30-7.38 2H, d, H-6, H-7); (7.17-7.25 3H, m, PhH); (6.95-7.02 4H, m, PhH); (6.84-6.87 2H, m, PhH); (6.92-6.94 2H, d, PhH); 5.48 (2H, s, NCH ₂Ph); 4.53 (2H, s, NCH ₂Ph).

9-ethyl-1-isopropyl-B-carboline (346): take 1-isopropyl-B-carboline and bromoethane as raw material, get white needle-like crystals, yield 77.3%, m.p.100-101 ℃; MS m/e 239; IR (KBr) ν: 1650-3100,1619.4,1557.7,1449.5,1411.7,1333.4,1250.7,1216.0,1089.4,1071.8,839.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.44-8.45 (1H, d, H-4); (8.12-8.14 1H, s, H-3); (7.83-7.84 1H, d, H-8) 7.57-7.61 (1H, t, H-5); (7.46-7.48 1H, t, H-6); (7.26-7.29 1H, t, H-7); 4.57-4.62 (2H, m, NCH ₂CH ₃); 3.75-3.79 (1H, m, NCH (CH ₃) ₂); 1.50-1.52 (6H, d, NCH (CH ₃) ₂); 1.46-1.50 (3H, t, NCH ₂CH ₃).

1-isopropyl-9-benzyl-B-carboline (347): take 1-isopropyl-B-carboline and cylite as raw material, get white needle-like crystals, yield 81.3%, m.p.126-128 ℃; MS m/e 301; IR (KBr) ν: 1650-3100,1618.6,1558.0,1450.1,1410.4,1353.0,1327.6,1196.1,1153.1,1075.4,994.8,827.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.47-8.49 (1H, d, H-4); (8.16-8.18 1H, d, H-3); (7.88-7.90 1H, d, H-8); (7.56-7.56 1H, t, H-5); (7.37-7.39 1H, d, H-6); (7.25-7.32 4H, m, H-7, PhH); (7.02-7.04 2H, m, PhH); 5.78 (2H, s, NCH ₂Ph); 3.61 (1H, m, NCH (CH ₃) ₂); 1.31-1.32 (6H, d, NCH (CH ₃) ₂).

1-isopropyl-9-(3-chlorobenzyl)-B-carboline (348): take 1-isopropyl-B-carboline and 3-chlorine cylite as raw material, get white crystal, yield 81.2%, m.p.93-95 ℃; MS m/e 336; IR (KBr) ν: 1650-3100,1619.2,1596.7,1574.7,1559.7,1457.4,1428.7,1373.3,1357.8,1329.2,1196.7,1158.0,1097.1,1073.5,772.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.49-8.50 (1H, d, H-4); (8.17-8.19 1H, d, H-3); (7.89-7.91 1H, d, H-8); (7.53-7.58 1H, t, H-5); (7.30-7.35 2H, m, H-6, H-7); (7.19-7.24 4H, m, PhH); (7.09 1H, s, PhH); (6.86-6.87 1H, d, PhH); 5.74 (2H, s, NCH ₂Ph); 3.52-3.56 (1H, m, NCH (CH ₃) ₂); 1.28-1.34 (6H, d, NCH (CH ₃) ₂).

9-ethyl-1-(4-chlorphenyl)-B-carboline (349): take 1-(4-chlorphenyl)-B-carboline and bromoethane as raw material, get white needle-like crystals, yield 79.4%, m.p.146-148 ℃; MS m/e 308; IR (KBr) ν: 1650-3100,1620.2,1595.4,1557.0,1447.1,1416.4,1278.3,1214.6,1126.5,1087.0,1051.8,1009.8,825.5,745.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.53 (1H, d, H-4); (8.19-8.21 1H, d, H-8); (7.99-8.01 1H, d, H-3); (7.62-7.64 1H, m, H-5); (7.57-7.61 2H, m, H-7, H-6); (7.50-7.53 2H, m, PhH); (7.46-7.48 1H, m, PhH); (7.31-7.35 1H, t, PhH); 4.07-4.02 (2H, m, NCH ₂CH ₃); 0.98-1.01 (3H, t, NCH ₂CH ₃). 9-butyl-1-(4-chlorphenyl)-B-carboline (350): take 1-(4-chlorphenyl)-B-carboline and iodo-n-butane as raw material, get white needle-like crystals, yield 81%, m.p.129-131 ℃; MS m/e 335; IR (KBr) ν: 1650-3100,1621.2,1599.8,1453.5,1450.3,1414.2,1395.4,1143.7,1201.4,1050.9,1014.0,1035.9,832.4,745.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.51 (1H, d, H-4); (8.19-8.17 1H, m, H-8); (8.00-7.99 1H, d, H-3); (7.62-7.60 1H, m, H-5); (7.59-7.58 1H, t, H-6); (7.57-7.56 1H, t, H-7); (7.52-7.51 1H, t, PhH); (7.50-7.49 1H, t, PhH); (7.46-7.44 1H, t, PhH); (7.33-7.29 1H, t, PhH); 4.00-3.96 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.38-1.31 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.92-0.86 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.69-0.65 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-hexyl-1-(4-chlorphenyl)-B-carboline (351): take 1-(4-chlorphenyl)-B-carboline and iodo normal hexane as raw material, get white crystal, yield 46%, m.p.108-110 ℃; MS m/e 362; IR (KBr) ν: 1650-3100,1620.3,1595.5,1493.3,1450.0,1414.4,1353.1,1318.0,1282.9,1233.4,1217.9,1183.0,1148.3,1033.5,828.7,788.0,750.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.51-8.53 (1H, d, H-4); (8.20-8.18 1H, d, H-8); (8.01-8.00 1H, d, H-3); (7.63-7.56 3H, m, H-5, H-6, H-7); (7.52-7.50 2H, d, PhH); (7.46-7.44 1H, d, PhH); (7.34-7.30 1H, m, PhH); 3.99-3.95 (2H, t, NCH ₂C ₅H ₁₀); 1.40-1.32 (2H, m, NCH ₂CH ₂C ₄H ₉); 1.16-1.03 (2H, m, NCH ₂CH ₂CH ₂C ₃H ₇); 1.01-0.96 (2H, m, NC ₃H ₆CH ₂CH ₂CH ₃); 0.90-0.86 (2H, m, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃); 0.84-0.78 (3H, t, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃).

1-(4-chlorphenyl)-9-benzyl-B-carboline (352): take 1-(4-chlorphenyl)-B-carboline and cylite as raw material, obtain white needle-like crystals, yield 44%, m.p.180-183 ℃; MS m/e 368; IR (KBr) ν: 1650-3100,1617.7,1554.0,1417.0,1445.2,1347.3,1310.4,1281.8,1235.4,1201.5,1150.9,1128.7,1039.7,1054.1,997.2,827.8,747.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.55-8.53 (1H, d, H-4); (8.25-8.23 1H, m, H-8); (8.05-8.04 1H, d, H-3); (7.58-7.54 1H, m, H-5); (7.37-7.35 1H, m, H-6); (7.34-7.33 1H, d, H-7); (7.32-7.31 1H, t, PhH); (7.30-7.29 1H, t, PhH); (7.26-7.26 1H, t, PhH); (7.25-7.24 1H, m, PhH); (7.17-7.11 3H, m, PhH); (6.59-6.58 2H, d, PhH); 5.50 (2H, s, NCH ₂Ph). 1-(4-chlorphenyl)-9-(2,3,4,5, the 6-PFBBR)-B-carboline (353): with 1-(4-chlorphenyl)-B-carboline and 2,3,4,5,6-five fluorine cylites are raw material, get white needle-like crystals, yield 36%, m.p.148-150 ℃; MSm/e 459; IR (KBr) ν: 1650-3100,1524.4,1501.2,1390.0,1314.1,1301.4,1205.7,1116.6,975.5,1009.1,743.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.59-8.58 (1H, d, H-4); (8.18-8.16 1H, d, H-8); (8.00-7.98 1H, d, H-3); (7.65-7.62 2H, m, H-5, H-6); (7.58-7.54 1H, m, H-7); (7.52-7.51 1H, t, PhH); (7.50-7.49 1H, t, PhH); (7.37-7.32 2H, m, PhH); 5.40 (2H, s, NCH ₂Ph).

1-(4-chlorphenyl)-9-(3-chlorobenzyl)-B-carboline (354): take 1-(4-chlorphenyl)-B-carboline and 3-chlorine cylite as raw material, get white crystal, yield 46%, m.p.128-130 ℃; MS m/e 403; IR (KBr) ν: 1650-3100,1620.7,1578.5,1491.4,1473.9,1445.4,1415.6,1392.0,1334.6,1312.2,1287.8,1238.6,1159.4,1093.9,1079.4,1012.3,996.2,882.2,825.9,783.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.56-8.55 (1H, d, H-4); (8.25-8.23 1H, d, H-8); (8.06-8.05 1H, d, H-3); (7.61-7.57 1H, t, H-5); (7.39-7.33 2H, m, H-6, H-7); (7.30-7.26 4H, m, PhH); (7.17-7.14 1H, d, PhH); (7.07-7.03 1H, t, PhH); (6.58-6.58 1H, s, PhH); (6.44-6.42 1H, d, PhH); 5.21 (2H, s, NCH ₂PhH).

1-(4-chlorphenyl)-9-(4-luorobenzyl)-B-carboline (355): take 1-(4-chlorphenyl)-B-carboline and 4-fluorine cylite as raw material, get white crystal, yield 46%, m.p.187-189 ℃; MS m/e 386; IR (KBr) ν: 1650-3100,1619.9,1556.2,1511.0,1445.7,1393.5,1338.5,1311.7,1279.9,1229.3,1201.6,1154.4,1129.2,1091.1,998.0,873.6,845.8,826.5,746.6cm ^-1; ¹H-NMR (CDCl3,400MHz) δ 8.55-8.53 (1H, d, H-4); (8.55-8.53 1H, d, H-8); (8.04-8.03 1H, d, H-3); (7.59-7.55 1H, t, H-5); (7.38-7.26 6H, m, H-6, H-7, PhH); (6.84-6.80 2H, m, PhH); (6.54-6.51 2H, m, PhH); 5.31 (2H, s, NCH ₂Ph).

1-(4-chlorphenyl)-9-phenylpropyl-B-carboline (356): take 1-(4-chlorphenyl)-B-carboline and 1-bromo-3-phenyl-propane as raw material, get white crystal, yield 45%, m.p.121-123 ℃; MS m/e 396; IR (KBr) ν: 1650-3100,1622.7,1613.6,1550.3,1495.4,1453.0,1391.0,1282.6,1244.5,1209.1,1177.8,1100.0,1077.7,1032.0,1013.2,911.0,829.8,785.2,745.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.51-8.50 (1H, d, H-4); (8.16-8.14 1H, d, H-8); (7.97-7.95 1H, d, H-3); (7.58-7.53 3H, m, H-5, H-6, H-7); (7.50-7.47 2H, m, PhH); (7.34-7.27 2H, m, PhH); (7.23-7.15 3H, m, PhH); (6.92-6.90 2H, m, PhH); 4.01-3.97 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.18-2.14 (2H, t, NCH ₂CH ₂CH ₂Ph); 1.70-1.62 (2H, m, NCH ₂CH ₂CH ₂Ph).

9-ethyl-1-(4-anisyl)-B-carboline (357): take 1-(4-methoxyphenyl)-B-carboline and bromoethane as raw material, obtain white needle-like crystals, yield 49.2%, m.p.125.2-126.2 ℃; MS m/e 303; IR (KBr) ν: 1650-3050,1612.3,1514.4,1445.1,1409.8,1367.0,1250.9,1220.1,1126.5,1035.1,832.1,785.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.51 (1H, d, H-4); (8.20-8.18 1H, d, H-8); (7.98-7.97 1H, d, H-3); (7.62-7.57 3H, m, H-5, H-6, H-7); (7.56-7.56 1H, d, PhH); (7.33-7.29 1H, m, PhH); (7.70-7.04 2H, m, PhH); 4.10-4.06 (2H, m, NCH ₂CH ₃); 3.92 (3H, s, OCH ₃); 1.01-0.98 (2H, t, NCH ₂CH ₃).

9-butyl-1-(4-anisyl)-B-carboline (358): take 1-(4-methoxyphenyl)-B-carboline and iodo-n-butane as raw material, obtain white needle-like crystals, yield 72.9%, m.p.117-118 ℃; MS m/e 331; IR (KBr) ν: 1650-3100,1612.6,1511.2,1448.7,1296.8,1240.7,1177.2,1030.7,831.5,746.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.53-8.52 (1H, d, H-4); (8.21-8.19 1H, d, H-8); (8.01-7.99 1H, d, H-3); (7.63-7.56 3H, m, H-5, H-6, H-7); (7.48-7.45 1H, d, PhH); (7.34-7.32 1H, d, PhH); (7.08-7.05 2H, m, PhH); 4.04-4.03 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.92 (3H, s, OCH ₃); 1.40-1.33 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.94-0.85 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.69-0.65 (2H, t, NCH ₂CH ₂CH ₂CH ₃);

9-hexyl-1-(4-anisyl)-B-carboline (359): take 1-(4-methoxyphenyl)-B-carboline and iodo normal hexane as raw material, get the white particulate crystal, yield 57.6%, m.p.109.0-110.1 ℃; MS m/e 359; IR (KBr) ν: 1650-3100,1610.8,1561.0,1514.0,1451.1,1414.3,1395.5,1370.0,1245.0,1219.6,1180.4,1034.4,830.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.51 (1H, d, H-4); (8.20-8.18 1H, d, H-8); (7.98-7.96 1H, d, H-3); (7.61-7.54 3H, m, H-5, H-6, H-7); (7.46-7.44 1H, d, PhH); (7.32-7.30 1H, d, PhH); (7.06-7.04 2H, d, PhH); 4.02-3.98 (2H, t, NCH ₂C ₅H ₁₁); 3.91 (3H, s, OCH ₃); 1.41-1.33 (2H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 1.16-1.09 (2H, m, NCH ₂CH ₂CH ₂(CH ₂) ₂CH ₃); 1.04-0.97 (2H, m, N (CH ₂) ₃CH ₂CH ₂CH ₃); 0.90-0.85 (2H, m, N (CH ₂) ₄CH ₂CH ₃); 0.81-0.77 (3H, t, NC ₅H ₁₀CH ₃);

9-octyl group-1-(4-anisyl)-B-carboline (360): take 1-(4-methoxyphenyl)-B-carboline and iodo normal octane as raw material, get white needle-like crystals, yield 61.9%, m.p.71-72 ℃; MS m/e 386; IR (KBr) ν: 1650-3100,1610.0,1511.7,1443.2,1413.3,1399.9,1241.4,1174.8,1031.0,830.8,746.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.51 (1H, d, H-4); (8.20-8.18 1H, d, H-8); (7.99-7.97 1H, d, H-3); (7.62-7.54 3H, m, H-5, H-6, H-7); (7.46-7.44 1H, d, PhH); (7.33-7.31 1H, d, PhH); (7.06-7.04 2H, m, PhH); 4.02-3.98 (2H, t, NCH ₂(CH ₂) ₆CH ₃); 3.91 (3H, s, OCH ₃); 1.39-1.35 (2H, m, NCH ₂CH ₂(CH ₂) ₅CH ₃); 1.24-1.20 (2H, m, NCH ₂CH ₂CH ₂(CH ₂) ₄CH ₃); 1.12-1.09 (4H, m, N (CH ₂) ₃CH ₂CH ₂CH ₂CH ₂CH ₃); 1.07-0.98 (2H, m, N (CH ₂) ₅CH ₂CH ₂CH ₃); 0.81-0.77 (5H, m, N (CH ₂) ₆CH ₂CH ₃).

1-(4-anisyl)-9-benzyl-B-carboline (361): take 1-(4-methoxyphenyl)-B-carboline and cylite as raw material, get white needle-like crystals, yield 53.6%, m.p.151-152 ℃; MS m/e 364; IR (KBr) ν: 1650-3050,1608.2,1513.5,1445.8,1401.3,1347.3,1310.7,1252.0,1201.0,1172.2,1036.6,996.2,836.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.54-8.53 (1H, d, H-4); (8.23-8.21 1H, d, H-8); (8.02-8.00 1H, d, H-3); (7.55-7.51 1H, t, H-5); (7.34-7.31 4H, m, H-6, H-7, PhH); (7.18-7.10 3H, m, PhH); (6.84-6.81 2H, m, PhH); (6.61-6.62 2H, d, PhH); 5.27 (2H, s, NCH ₂Ph); 3.91 (3H, s, OCH ₃).

1-(4-anisyl)-9-(2,3,4,5, the 6-PFBBR)-B-carboline (362): with 1-(4-methoxyphenyl)-B-carboline and 2,3,4,5,6-five fluorine cylites are raw material, get white needle-like crystals, yield 56.1%, m.p.159-161 ℃; MS m/e 454; IR (KBr) ν: 3100,1655,1609.6,1499.5,1450.7,1244.8,1206.3,1176.9,1113.7,1003.0,976.0,935.6,831.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.58-8.57 (1H, d, H-4); (8.18-8.16 1H, d, H-8); (7.97-7.96 1H, d, H-3); (7.61-7.59 2H, m, H-5, H-6); (7.55-7.54 1H, d, H-7); (7.36-7.31 2H, m, PhH); (7.05-7.03 2H, d, PhH); 5.44 (2H, s, NCH ₂Ph); 3.89 (3H, s, OCH ₃).

1-(4-anisyl)-9-(4-luorobenzyl)-B-carboline (363): take 1-(4-methoxyphenyl)-B-carboline and 4-fluorine cylite as raw material, get white needle-like crystals, yield 37.9%, m.p.141-143 ℃; MS m/e 382; IR (KBr) ν: 1650-3050,11607.4,1558.6,1510.5,1445.3,1400.7,1337.9,1310.7,1248.6,1201.0,1172.4,1128.9,1042.7,1000.2,874.2,842.4,747.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.55-8.53 (1H, d, H-4); (8.23-8.21 1H, d, H-8); (8.02-8.01 1H, d, H-3); (7.58-7.54 1H, t, H-5); (7.55-7.54 4H, m, H-6, H-7, PhH); (6.87-6.85 2H, m, PhH); (6.80-6.78 2H, m, PhH); (6.58-6.54 2H, m, PhH); 5.24 (2H, s, NCH ₂Ph); 3.91 (3H, s, OCH ₃).

1-(4-anisyl)-9-(3-chlorobenzyl)-B-carboline (364): take 1-(4-methoxyphenyl)-B-carboline and 3-chlorine cylite as raw material, get yellow granular crystal, yield 56.6%, m.p.115-116 ℃; MS m/e 398; IR (KBr) ν: 1650-3100,1621.0,1575.4,1514.1,1474.2,1452.4,1415.5,1363.3,1314.8,1243.6,1203.8,1132.1,1076.8,1021.9,879.7,832.6,780.2,744.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.55-8.53 (1H, d, H-4); (8.24-8.22 1H, d, H-8); (8.02-8.01 1H, d, H-3); (7.59-7.54 1H, t, H-5); (7.37-7.27 4H, m, H-6, H-7, PhH); (7.14-7.12 1H, d, PhH); (7.04-7.00 1H, t, PhH); (6.86-6.84 2H, m, PhH); (6.60 1H, s, PhH); (6.45-6.43 1H, d, PhH); 5.23 (2H, s, NCH ₂Ph); 3.91 (3H, s, OCH ₃).

9-ethyl-1-(2-chloro-5-nitrobenzophenone)-B-carboline (365): take 1-(2-chloro-5-nitrobenzophenone)-B-carboline and bromoethane as raw material, get faint yellow solid, yield 77%, m.p.72-74 ℃; MS m/e 351; IR (KBr) ν: 1650-3100,1618.9,1566.7,1531.3,1475.7,1446.0,1416.6,1355.2,1304.4,1216.7,1150.4,1130.7,1069.4,1046.5,1023.2,896.3,825.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.55-8.57 (1H, d, H-4); (8.50-8.50 1H, d, H-8); (8.33-8.36 1H, d, H-3); (8.22-8.24 1H, d, H-5); (8.11-8.12 1H, d, H-6); (7.74-7.76 1H, d, H-7); (7.63-7.67 1H, t, PhH); (7.45-7.47 1H, d, PhH); (7.34-7.38 1H, t, PhH); 3.84-4.07 (2H, m, NCH ₂CH ₃); 1.03-1.07 (3H, t, NCH ₂CH ₃).

9-butyl-1-(2-chloro-5-nitrobenzophenone)-B-carboline (366): take 1-(2-chloro-5-nitrobenzophenone)-B-carboline and iodo-n-butane as raw material, get yellow solid, yield 54.5%, IR (KBr) ν: 1650-3050,1623.4,1573.5,1530.6,1495.4,1470.9,1433.7,1347.2,1237.6,1204.1,1144.9,1130.4,1081.5,911.6,861.7,821.4,779.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.97-8.98 (1H, d, H-4); (8.89-8.90 1H, d, H-8); (8.76-8.77 1H, d, H-3); (8.60-8.64 2H, m, H-5, H-6); (8.16-8.19 1H, d, H-7); (7.85-7.87 2H, m, PhH); (7.51-7.55 1H, t, PhH); 4.07-4.15 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.33-1.43 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.77-0.95 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.58-0.62 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-7:

The general synthesis techniques of 1,2,9-, three replacement-beta-carboline derivatives (367-382):

1,9-, two replacement-B-carbolines (10mmol) add the 50ml ethyl acetate it are dissolved fully, add corresponding halogenated alkane (15-30mmol), and reflux 1-8 hour, be cooled to room temperature, filter the solid of separating out.Solid washs with a small amount of ethyl acetate, subsequently solid is dissolved in the dehydrated alcohol, and reflux is to clarification, and filtered while hot is placed the refrigerator recrystallization, gets crystal.

9-ethyl-1,2-dibenzyl-B-carboline bromine salt (367): take 9-ethyl-1-benzyl-B-carboline and cylite as raw material, get yellow crystals, yield 79.4%, m.p.208-210 ℃; MS:m/e 286; IR (KBr) ν: 1650-3050,1621.7,1452.7,1339.9,1234.0,1162.9,1052.6,816.3cm ^-1; ¹H-NMR (DMSO-d6,400MHz) δ 8.95-8.99 (2H, dd, H-4, H-8); (8.61-8.63 1H, d, H-3); (7.88-7.93 2H, m, H-5, H-6); (7.54-7.58 1H, m, H-7); (7.09-7.38 10H, m, PhH); 5.98 (2H, s, CH ₂Ph); 4.97 (2H, s, NCH ₂Ph); 4.48-4.53 (2H, m, NCH ₂CH ₃); 1.20-1.24 (3H, t, NCH ₂CH ₃).

9-butyl-1,2-dibenzyl-B-carboline bromine salt (368): take 9-butyl-1-benzyl-B-carboline and cylite as raw material, get yellow crystals, yield 69.2%, m.p.164-165 ℃; MS:m/e 313; IR (KBr) ν: 1650-3050,1622.6,1575.8,1454.5,1340.2,1242.0,1162.3,1054.5,811.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.95-8.98 (2H, dd, H-4, H-8); (8.61-8.63 1H, d, H-3); (7.90-7.91 2H, m, H-5, H-6); (7.54-7.58 1H, m, H-7); (7.07-7.38 10H, m, PhH); 5.97 (2H, s, CH ₂Ph); 4.97 (2H, s, NCH ₂Ph); 4.38-4.42 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.53-1.55 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.16-1.19 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.71-0.75 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-hexyl-1,2-dibenzyl-B-carboline bromine salt (369): take 9-hexyl-1-benzyl-B-carboline and cylite as raw material, get yellow crystals, yield 85.2%, m.p.204-206 ℃; IR (KBr) ν: 1650-3050,1623.7,1576.9,1455.0,1340.2,1240.6,1167.1,1055.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.94-8.98 (2H, dd, H-4, H-8); (8.60-8.62 1H, d, H-3); (7.90-7.93 2H, m, H-5, H-6); (7.54-7.58 1H, m, H-7); (7.07-7.36 10H, m, PhH); 5.97 (2H, s, CH ₂Ph); 4.97 (2H, s, NCH ₂Ph); 4.39-4.43 (2H, t, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃); 1.55 (2H, m, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃); 1.05-1.15 (6H, m, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃); 0.76-0.79 (3H, t, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃).

1,2-dibenzyl-9-(4-luorobenzyl)-B-carboline bromine salt (370): take 1-benzyl-9-(4-luorobenzyl)-B-carboline and cylite be as raw material, gets white crystal, yield 75.2%, m.p.165-167 ℃; MS:m/e 256; IR (KBr) ν: 1650-3050,1623.5,1577.1,1493.5,1456.5,1221.2,1159.3,1055.0,822.8cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.98-9.05 (2H, dd, H-4, H-8); (8.67-8.69 1H, d, H-3); (7.86-7.90 1H, m, H-5); (7.78-7.80 1H, d, H-6); (7.57-7.61 1H, t, H-7); (7.22-7.46 7H, m PhH); (6.89-7.09 7H, m, PhH); 5.91 (2H, s, CH ₂Ph); 5.71 (2H, s, NCH ₂Ph); 4.70-4.74 (2H, d, NCH ₂Ph).

2,9-dibenzyl-1-(4-chlorphenyl)-B-carboline bromine salt (371): take 9-benzyl-1-(4-chlorphenyl)-B-carboline and cylite be as raw material, gets pale yellow crystals, yield 86.2%, m.p.230-232 ℃; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.12-9.04 (2H, m, H-4, H-8); (8.71-8.69 1H, d, H-3); (7.84-7.82 1H, m, H-5); (7.69-7.67 1H, d, H-6); (7.59-7.56 1H, t, H-7); (7.37-7.32 4H, m, PhH); (7.31-7.28 3H, m, PhH); (7.19-7.13 3H, m, PhH); (6.90-6.88 2H, d, PhH); (6.60-6.58 2H, d, PhH); 5.58 (2H, s, NCH ₂Ph); 5.10 (2H, s, NCH ₂Ph).

2-benzyl-1-(4-chlorphenyl)-9-(4-luorobenzyl)-B-carboline bromine salt (372): take the 9-(4-luorobenzyl)-the 1-(4-chlorphenyl)-B-carboline and cylite be raw material, get yellow crystals, yield 86.2%, m.p.224-226 ℃; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.14-9.06 (2H, m, H-4, H-8); (8.72-8.70 1H, d, H-3); (7.86-7.84 1H, t, H-5); (7.72-7.70 1H, d, H-6); (7.61-7.57 1H, t, H-7); (7.34-7.30 4H, m, PhH); (7.29-7.27 4H, m, PhH); (7.25-7.18 1H, m, PhH); (6.91-6.88 2H, d, PhH); (6.68 1H, s, PhH); (6.53-6.51 1H, d, PhH); 5.64 (2H, s, NCH ₂Ph); 5.14 (2H, s, NCH ₂Ph).

9-butyl-2-benzyl-1-(2-chlorphenyl)-B-carboline bromine salt (373): take 9-butyl-1-(2-chlorphenyl)-B-carboline and cylite be as raw material, gets pale yellow crystals, yield 69.7%, m.p.211-213 ℃; MS:m/e334; IR (KBr) ν: 1650-3050,1622.1,1575.1,1457.1,1341.2,1243.0,1162.3,1054.6,811.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.22-9.14 (2H, m, H-4, H-8); (8.69-8.67 1H, d, H-3); (7.94-7.76 5H, m, H-5, H-6, H-7, PhH); (7.68-7.64 1H, t, PhH); (7.59-7.55 1H, m, PhH); (7.34-7.25 3H, m, PhH); (6.92-6.90 2H, d, PhH); 5.87 (2H, s, NCH ₂Ph); 3.94-3.48 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.36-1.32 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.90-0.78 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.68-0.64 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-butyl-1-(2-chlorphenyl)-2-(4-luorobenzyl)-B-carboline bromine salt (374): take 9-butyl-1-(2-chlorphenyl)-B-carboline and 4-fluorine cylite be as raw material, gets pale yellow crystals, yield 81.4%, m.p.107-109 ℃; MS:m/e 334; IR (KBr) ν: 1650-3050,1621.8,1574.5,1468.3,1338.5,1222.3,1156.3,1053.4,834.8cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.25-9.14 (2H, m, H-4, H-8); (8.69-8.67 1H, d, H-3); (7.93-7.83 4H, m, H-5, H-6, H-7, PhH); (7.78-7.76 1H, d, PhH); (7.71-7.67 1H, d, PhH); (7.59-7.55 1H, m, PhH); (7.13-7.09 2H, d, PhH); (6.97-6.93 2H, m, PhH); 5.86 (2H, s, NCH ₂Ph); 3.96-3.41 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.34-1.37 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.90-0.79 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.68-0.64 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

2,9-dibutyl-1-(2-chlorphenyl)-B-carboline iodine salt (375): take 9-butyl-1-(2-chlorphenyl)-B-carboline and iodo-n-butane be as raw material, gets pale yellow crystals, yield 82.6%, m.p.176-178 ℃; MS:m/e334; IR (KBr) ν: 1650-3050,1622.1,1573.1,1464.7,1340.9,1211.3,1139.5,1053.6,858.1cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.13 (2H, s, H-4, H-8); (8.69-8.67 1H, d, H-3); (8.23-8.21 1H, d, H-5); (8.01-7.90 4H, m, H-6, H-7, PhH); (7.87-7.83 1H, t, PhH); (7.60-7.56 1H, m, PhH); 4.60-4.21 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.96-3.88 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.83-1.79 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.43-1.36 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.28-1.18 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.96-0.83 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.78-0.64 (6H, m, NCH ₂CH ₂CH ₂CH ₃).

2-butyl-9-benzyl-1-(2-chlorphenyl)-B-carboline bromine salt (376): take 9-benzyl-1-(2-chlorphenyl)-B-carboline and iodo-n-butane be as raw material, gets pale yellow crystals, yield 83.2%, m.p.173-175 ℃; MS:m/e 368; IR (KBr) ν: 1650-3050,1621.2,1574.1,1455.3,1338.1,1212.3,1135.1,1057.1,837.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.16-9.10 (2H, m, H-4, H-8); (8.72-8.70 1H, d, H-3); (7.86-7.79 1H, d, H-5, H-6); (7.76-7.67 3H, m, H-7, PhH); (7.59-7.56 1H, t, PhH); (7.48-7.44 1H, m, PhH); (7.21-7.11 3H, m, PhH); (6.56-6.54 2H, d, PhH); 5.31-5.01 (2H, m, NCH ₂Ph); 4.52-4.12 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.79-1.73 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.20-1.13 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.68-0.65 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

2,9-dibenzyl-1-(2-chlorphenyl)-B-carboline bromine salt (377): take 9-benzyl-1-(2-chlorphenyl)-B-carboline and cylite be as raw material, gets pale yellow crystals, yield 91.4%, m.p.190-192 ℃; MS:m/e 368; IR (KBr) ν: 1650-3060,1620.2,1576.1,1456.2,1339.7,1210.2,1147.1,1056.7,821.6cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.26-9.21 (2H, m, H-4, H-8); (8.75-8.73 1H, d, H-3); (7.88-7.84 1H, t, H-5); (7.73-7.71 1H, d, H-6); (7.68-7.64 1H, t, H-7), 7.61-7.58 (1H, t, PhH); (7.53-7.48 2H, t, PhH); (7.32-7.23 4H, m, PhH); (7.19-7.10 3H, m, PhH); (6.89-6.87 2H, d, PhH); (6.53-6.51 2H, d, PhH); 5.83-5.57 (2H, m, NCH ₂Ph); 5.32-4.96 (2H, m, NCH ₂Ph).

9-benzyl-1-(2-chlorphenyl)-2-(4-luorobenzyl)-B-carboline bromine salt (378): take 9-benzyl-1-(2-chlorphenyl)-B-carboline and 4-fluorine cylite be as raw material, gets pale yellow crystals, yield 79.5%, m.p.174-176 ℃; MS:m/e 368; IR (KBr) ν: 1650-3050,1621.6,1576.1,1465.8,1338.1,1223.9,1155.4,1055.7,834.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.27-9.21 (2H, d, H-4, H-8); (8.75-8.73 1H, d, H-3); (7.88-7.83 1H, m, H-5); (7.73-7.65 2H, m, H-6, H-7), 7.62-7.51 (3H, m, PhH); (7.35-7.31 1H, t, PhH); (7.19-7.07 5H, m, PhH); (6.94-6.91 2H, t, PhH); (6.53-6.49 2H, t, PhH); 5.80-5.59 (2H, m, NCH ₂Ph); 5.40-4.93 (2H, m, NCH ₂Ph).

2-benzyl-1-(2-chlorphenyl)-9-(4-luorobenzyl)-B-carboline bromine salt (379): take 9-(4-luorobenzyl)-1-(2-chlorphenyl)-B-carboline and cylite as raw material, get pale yellow crystals, yield 86.1%, m.p.119-121 ℃; MS:m/e 386; IR (KBr) ν: 1650-3050,1622.2,1574.5,1463.1,1337.8,1219.6,1154.4,1053.6,822.5cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.19-9.24 (2H, d, H-4, H-8); (8.74-8.72 1H, d, H-3); (7.89-7.86 1H, t, H-5); (7.74-7.72 1H, d, H-6); (7.69-7.65 1H, t, H-7), 7.64-7.59 (1H, t, PhH); (7.58-7.49 2H, m, PhH); (7.49-7.38 1H, m, PhH); (7.35-7.24 3H, m, PhH); (6.98-6.87 4H, m, PhH); (6.57-6.47 2H, m, PhH); 5.82-5.55 (2H, m, NCH ₂Ph); 5.29-4.97 (2H, m, NCH ₂Ph).

2,9-two (4-luorobenzyl)-1-(2-chlorphenyl)-B-carboline bromine salt (380): take 9-(4-luorobenzyl)-1-(2-chlorphenyl)-B-carboline and 4-fluorine cylite as raw material, get pale yellow crystals, yield 83.6%, m.p.183-185 ℃; MS:m/e 386; IR (KBr) ν: 1650-3050,1621.5,1576.4,1464.8,1339.1,1223.9,1155.6,1056.1,820.1cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.37-9.33 (1H, m, H-4); (9.30-9.28 1H, d, H-8); (8.79-8.77 1H, d, H-3); (7.91-7.86 1H, t, H-5); (7.77-7.75 1H, d, H-6); (7.72-7.67 1H, m, H-7), 7.63-7.55 (3H, m, PhH); (7.41-7.25 2H, m, PhH); (7.14-7.09 1H, t, PhH); (7.00-6.91 4H, m, PhH); (6.61-6.58 2H, t, PhH); 5.88-5.60 (2H, m, NCH ₂Ph); 5.34-4.96 (2H, m, NCH ₂Ph).

2,9-dibenzyl-1-(4-methoxyl group) phenyl-B-carboline bromine salt (381): take 9-benzyl-1-(4-methoxyl group) phenyl-B-carboline and cylite as raw material, get yellow crystals, yield 73.8%, m.p.111-112 ℃; MS:m/e364; IR (KBr) ν: 1650-3050,1622.6,1574.9,1455.3,1338.2,1254.6,1150.1,1067.7,837.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 9.01-9.08 (2H, dd, H-4, H-8); (8.67-8.69 1H, d, H-3); (7.79-7.84 1H, m, H-5); (7.64-7.66 1H, d, H-6); (7.54-7.58 1H, m, H-7); (7.13-7.30 8H, m, PhH); (6.84-6.93 4H, m, PhH); (6.61-6.63 2H, t, PhH); 5.66 (2H, s, NCH ₂Ph); 5.09 (2H, s, NCH ₂Ph); 3.78 (3H, s, OCH ₃).

9-ethyl-1-(4-methoxyl group) phenyl-2-benzyl-B-carboline bromine salt (382): take 9-ethyl-1-(4-methoxyl group) phenyl-B-carboline and cylite as raw material, get yellow crystals, yield 79.5%, MS:m/e 302; M.p.134-136 ℃; IR (KBr) ν: 3421.5,1650-3050,1621.8,1571.2,1453.8,1338.8,1233.8,1157.8,1064.8,845.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.93-8.99 (2H, dd, H-4, H-8); (8.62-8.64 1H, d, H-3); (7.85-7.92 2H, m, H-5, H-6); (7.54-7.58 3H, m, H-7, PhH); (7.16-7.32 5H, m, PhH); (6.94-6.97 2H, t, PhH); 5.69 (2H, s, NCH ₂Ph); 3.88 (3H, s, OCH ₃); 3.76-3.77 (2H, m, NCH ₂CH ₃); 0.93-0.96 (3H, t, NCH ₂CH ₃).

9-butyl-1-(4-methoxyl group) phenyl-2-benzyl-B-carboline bromine salt (383): take 9-butyl-1-(4-methoxyl group) phenyl-B-carboline and cylite as raw material, get yellow crystals, yield 82.7%, m.p.111-112 ℃; MS:m/e 330; IR (KBr) ν: 3421.2,1650-3050,1619.9,1568.3,1425.8,1341.9,1256.5,1147.4,1063.3,842.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.93-8.99 (2H, dd, H-4, H-8); (8.61-8.63 1H, d, H-3); (7.87-7.89 2H, m, H-5, H-6); (7.53-7.58 3H, m, H-7, PhH); (7.16-7.32 5H, m, PhH); (6.93-6.95 2H, m, PhH); 5.69 (2H, s, NCH ₂Ph); 3.87 (3H, s, OCH ₃); 3.67-3.72 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.32-1.34 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.84-0.89 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.69-0.72 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-8:(synthetic route is unclear, has made corresponding modification)

1,9-two replaces the general synthesis technique of beta-carboline derivatives (384-390):

1-(2-thienyl)-9-benzyl-B-carboline (384): take 1-(2-thienyl)-B-carboline and cylite as raw material, get white crystal, yield 78.5%, m.p.148-149 ℃; MS:m/e 340; ¹H-NMR (CDCl ₃, 400MHz) δ 8.55-8.57 (1H, d, H-3); (8.22-8.24 1H, d, H-5); (8.05-8.07 1H, d, H-4); (7.54-7.58 1H, m, H-8); (7.43-7.45 1H, d, H-6); (7.33-7.37 2H, m, H-7, PhH); (7.15-7.19 3H, m, PhH); (7.03-7.04 1H, m, PhH); (6.96-6.98 1H, m, ArH); (6.72-6.74 2H, m, ArH); 5.40 (2H, s, NCH ₂Ph).

1-(2-thienyl)-9-phenylpropyl-B-carboline (385): take 1-(2-thienyl)-B-carboline and 1-bromo-3-phenyl-propane as raw material, get white crystal, yield 72.5%, m.p.146-148 ℃; MS:m/e 368; ¹H-NMR (CDCl ₃, 400MHz) δ 8.52-8.53 (1H, d, H-3); (8.15-8.17 1H, d, H-5); (7.98-7.99 1H, d, H-4); (7.54-7.59 2H, m, H-8, H-6); (7.28-7.36 3H, m, H-7, PhH); (7.17-7.25 4H, m, PhH); (6.98-7.00 2H, m, ArH); 4.13-4.17 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.29-2.25 (2H, m, NCH ₂CH ₂CH ₂Ph); 1.76-1.81 (2H, t, NCH ₂CH ₂CH ₂Ph).

9-butyl-1-(2-thienyl)-B-carboline (386): take 1-(2-thienyl)-B-carboline and iodo-n-butane as raw material, get white crystal, yield 83.4%, m.p.131-133 ℃; MS:m/e 306; ¹H-NMR (CDCl ₃, 400MHz) δ 8.58-8.60 (1H, d, H-3); (8.04-8.07 1H, d, H-5); (7.91-7.93 1H, d, H-4); (7.59-7.62 2H, m, H-8, H-6); (7.33-7.35 1H, m, H-7); (7.14-7.19 2H, m, ArH); (6.98-7.01 1H, m, ArH); 3.69-3.73 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.45-1.49 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.84-0.89 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.63-0.66 (3H, m, NCH ₂CH ₂CH ₂CH ₃).

9-benzyl-1-(3-pyridine radicals)-B-carboline (387): take 1-(3-pyridine radicals)-B-carboline and cylite as raw material, get the milky crystal, yield 82.7%, m.p.148-149 ℃; MS:m/e 335; IR (KBr) ν: 1650-3050,1619.1,1470.3,1447.3,1365.4,1200.2,1161.3,1043.3,837.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.58-8.68 (3H, m, H-5, H-3, H-4); (8.26-8.28 1H, m, H-8); (8.13-8.14 1H, m, H-6); (7.59-7.64 2H, m, H-7, Py-H); (7.37-7.42 2H, m Py-H); (7.08-7.21 4H, m, Py-H, Ph-H); (6.47-6.49 2H, d, Ph-H); 5.28 (2H, s, NCH ₂Ph).

9-(4-luorobenzyl)-1-(3-pyridine radicals)-B-carboline (388): take 1-(3-pyridine radicals)-B-carboline and 4-fluorine cylite as raw material, get the milky crystal, yield 84.2%, m.p.162-163 ℃; MS:m/e 353; ¹H-NMR (CDCl ₃, 400MHz) δ 8.69-8.71 (2H, d, H-5, H-3); (8.59-8.60 1H, d, H-4); (8.26-8.28 1H, d, H-8); (8.11-8.13 1H, d, H-6); (7.60-7.64 2H, m, H-7, Py-H); (7.38-7.42 2H, m, Py-H); (7.26 1H, s, Py-H); (6.78-6.82 2H, t, Ph-H); (6.42-6.45 2H, t, Ph-H); 5.25 (2H, s, NCH ₂Ph).

9-ethyl-1-(3-pyridine radicals)-B-carboline (389): take 1-(3-pyridine radicals)-B-carboline and bromoethane as raw material, get pale yellow crystals, yield 78.7%, m.p.155-156 ℃; MS:m/e 273; IR (KBr) ν: 1650-3050,1620.2,1479.7,1445.3,1353.2,1214.7,1191.8,1044.4,841.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.90-8.91 (1H, d, H-5); (8.76-8.78 1H, d, H-3); (8.55-8.57 1H, d, H-4); (8.20-8.22 1H, d, H-8); (8.04-8.05 1H, d, H-6); (7.99-8.02 1H, m, H-7); (7.61-7.65 1H, m, Py-H); (7.46-7.51 2H, m Py-H); (7.32-7.36 1H, t, Py-H); 4.02-4.07 (2H, m, NCH ₂CH ₃); 0.99 (3H, s, NCH ₂CH ₃).

9-butyl-1-(3-pyridine radicals)-B-carboline (390): take 1-(3-pyridine radicals)-B-carboline and iodo-n-butane as raw material, get pale yellow crystals, yield 85.1%, m.p.133-135 ℃; MS:m/e 301; ¹H-NMR (CDCl ₃, 400MHz) δ 8.89-8.90 (1H, d, H-5); (8.76-8.77 1H, d, H-3); (8.55-8.57 1H, d, H-4); (8.19-8.22 1H, d, H-8); (8.04-8.05 1H, d, H-6); (7.98-8.01 1H, m, H-7); (7.60-7.64 1H, m, Py-H); (7.45-7.51 2H, m Py-H); (7.31-7.35 1H, t, Py-H); 3.97-4.01 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.32-1.37 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.86-0.91 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.64-0.67 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-9:

The general synthesis technique (391-406) of 1,9-, two replacement-B-carbolines-3-carboxylic acid, ethyl ester alcaloid-derivatives:

Get 1-replacement-B-carboline-3-carboxylic acid, ethyl ester (10mmol) in 100 milliliters round-bottomed flask, add 60 milliliters DMF and shake up and make as far as possible its dissolving, add again alkyl halide (15mmol), add NaH (15mmol), magnetic agitation.TLC monitoring reaction process was surveyed once every 30 minutes, after the raw material complete reaction, and stopped reaction.Reactant liquor poured into use ethyl acetate extraction in the suitable quantity of water, extract with except emulsifying, adds an amount of ethanol and concentrated hydrochloric acid with saturated sodium chloride solution washing 2 times, leave standstill, be concentrated into driedly, add the proper amount of acetone crystallization, the cooling crystallize out, filter to get solid, use water dissolution, the sodium bicarbonate alkalization adds ethyl acetate extraction, extract adds anhydrous sodium sulfate drying, activated carbon decolorizing is placed and after about 5 hours extract is crossed silica gel G and remove impurity, has been concentrated into a small amount of crystal and has separated out, cold preservation was placed 35 hours, crystallize out filters, washing, drying namely gets product.

9-hexyl-B-carboline-3-carboxylic acid, ethyl ester (391): take B-carboline-3-carboxylic acid, ethyl ester and iodo normal hexane as raw material, get the pale solid powder, yield 61.3%, m.p.77.3-79.7 ℃; MS m/e 325; IR (KBr) ν: 1650-3100,1551.7,1501.5,1463.5,1367.2,1130.5,1243.5,1218.0,1205.2,1104.7,789.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.91-8.97 (2H, d, H-4, H-1); (8.22-8.24 1H, d, H-8); (7.64-7.68 1H, t, H-5); (7.52-7.54 1H, d, H-6); (7.35-7.39 1H, t, H-7); 4.53-4.58 (2H, m, COOCH ₂CH ₃); 4.42-4.46 (2H, t, NCH ₂(CH ₂) ₄CH ₃); 1.89-1.96 (2H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 1.50-1.53 (3H, t, COOCH ₂CH ₃); 1.24-1.39 (6H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 0.83-0.87 (2H, t, NCH ₂(CH ₂) ₄CH ₃).

9-(3-chlorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (392): take B-carboline-3-carboxylic acid, ethyl ester and 3-chlorine cylite as raw material, get white crystal, yield 70.2%, m.p.128-129 ℃; MS m/e 364; IR (KBr) ν: 1650-3100,1624.3,1585.1,1554.1,1471.5,1468.1,1429.3,1334.2,1303.8,1219.2,1106.8,1024.4,1003.8,770.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.90-8.93 (2H, d, H-4, H-1); (8.25-8.27 1H, d, H-8); (7.62-7.66 1H, t, H-5); (7.47-7.49 1H, d, H-6); (7.39-7.43 1H, t, H-7); (7.24-7.27 1H, m, PhH); (7.21-7.23 1H, m, PhH); (7.15-7.16 1H, s, PhH); (6.99-7.02 1H, d, PhH); 5.60 (2H, m, NCH ₂Ph); 4.55-4.60 (2H, m, COOCH ₂CH ₃); 1.47-1.49 (3H, t, COOCH ₂CH ₃).

9-(4-luorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (393): take B-carboline-3-carboxylic acid, ethyl ester and 4-fluorine cylite as raw material, get white crystal, yield 77.1%, m.p.123-124 ℃; MS m/e 348; IR (KBr) ν: 1650-3050,1511.3,1469.1,1372.8,1293.0,1271.7,1157.9,1108.2,1025.6,788.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.94-8.99 (2H, m, H-4, H-1); (8.25-8.27 1H, d, H-8); (7.62-7.66 1H, t, H-5); (7.49-7.51 1H, d, H-6); (7.39-7.42 1H, d, H-7); (7.12-7.15 2H, m, PhH); (6.95-6.99 2H, m, PhH); 5.57 (2H, s, NCH ₂Ph); 4.52-4.55 (2H, m, COOCH ₂CH ₃); 1.48-1.52 (3H, t, COOCH ₂CH ₃).

9-ethyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester (394): take 1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and bromoethane as raw material, get white crystal, yield 62%, m.p.176-178 ℃; MS m/e 379; IR (KBr) ν: 1650-3100,1620.8,1557.7,1492.9,1468.9,1446.1,1368.1,1344.5,1314.1,1298.2,1273.1,1155.0,1135.0,1084.5,917.3,867.7,847.6,833.5,773.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.89 (1H, s, H-4); (8.27-8.25 1H, d, H-8); (7.67-7.58 3H, m, H-5, H-6, H-7); (7.52-7.49 3H, m, PhH); (7.41-7.37 1H, t, PhH); 4.55-4.49 (2H, m, COOCH ₂CH ₃); 4.07-4.02 (2H, m, NCH ₂CH ₃); 1.49-1.45 (3H, t, COOCH ₂CH ₃); 1.04-1.00 (3H, t, NCH ₂CH ₃).

9-butyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester (395): take 1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and iodo-n-butane as raw material, get white crystal, yield 81%, m.p.155-158 ℃; MS m/e406; IR (KBr) ν: 1650-3100,1619.5,1554.7,1488.9,1465.8,1367.8,1347.6,1300.1,1255.4,1134.2,1086.1,924.9,903.2,844.9,829.2,792.0,744.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.89 (1H, s, H-4); (8.27-8.25 1H, d, H-8); (7.66-7.58 3H, m, H-5, H-6, H-7); (7.51-7.48 3H, m, PhH); (7.40-7.36 1H, t, PhH); 4.55-4.49 (2H, m, COOCH ₂CH ₃); 4.01-3.97 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.49-1.45 (3H, t, COOCH ₂CH ₃); 1.38-1.34 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.91-0.86 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.69-0.66 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-benzyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester (396): take 1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and cylite as raw material, get white crystal, yield 77%, m.p.135-137 ℃; MS m/e 440; IR (KBr) ν: 1650-3100,1621.3,1597.7,1555.7,1492.3,1453.0,1389.5,1367.6,1345.9,1267.1,1233.7,1154.4,1110.5,1089.5,1051.3,1015.1,970.8,867.3,832.4,790.3,740.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.93 (1H, s, H-4); (8.31-8.29 1H, d, H-8); (7.61-7.57 1H, t, H-5); (7.42-7.37 2H, m, H-7, H-6); (7.33-7.30 2H, d, PhH); (7.25-7.22 2H, m, PhH); (7.17-7.11 3H, m, PhH); (6.56-6.54 2H, d, PhH); 5.25 (2H, s, NCH ₂Ph); 4.54-4.46 (2H, m, COOCH ₂CH ₃); 1.51-1.41 (3H, t, COOCH ₂CH ₃).

1-(4-chlorphenyl)-9-(4-luorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (397): take 1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and 4-fluorine cylite as raw material, obtain white crystal, yield 79%, m.p.118-120 ℃; MS m/e 458; IR (KBr) ν: 1650-3100,1620.9,1600.5,1555.9,1491.0,1455.5,1390.8,1367.7,1345.5,1267.7,1230.2,1157.8,1110.6,1088.7,1051.7,1015.0,870.8,833.0,790.2,743.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.93 (1H, s, H-4); (8.31-8.29 1H, d, H-8); (7.62-7.58 1H, t, H-5); (7.43-7.27 6H, m, H-7, H-6, PhH); (6.84-6.80 2H, t, PhH); (6.51-6.48 2H, t, PhH); 5.23 (2H, s, NCH ₂Ph); 4.54-4.49 (2H, m, COOCH ₂CH ₃); 1.48-1.45 (3H, t, COOCH ₂CH ₃).

9-ethyl-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester (398): take 1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester and bromoethane as raw material, get the white particulate crystal, yield 81.2%, m.p.167-168 ℃; MS m/e 374; IR (KBr) ν: 1650-3100,1608.2,1511.8,1450.2,1396.9,1371.1,1347.9,1291.2,1275.6,1244.4,1178.5,1134.2,1108.8,1049.4,1029.7,849.6,816.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.87-8.82 (1H, t, H-4); (8.26-8.24 1H, t, H-8); (7.65-7.61 1H, t, H-5); (7.65-7.61 2H, m, H-7, H-6); (7.56-7.48 2H, d, PhH); (7.39-7.35 1H, t, PhH); (7.06-7.03 2H, m, PhH); 4.54-4.49 (2H, m, COOCH ₂CH ₃); 4.09-4.04 (2H, m, NCH ₂CH ₃); 3.90 (3H, s, OCH ₃); 1.49-1.45 (3H, t, COOCH ₂CH ₃); 1.02-0.99 (3H, t, NCH ₂CH ₃).

9-butyl-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester (399): take 1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester and iodo-n-butane as raw material, get the white particulate crystal, yield 58.7%, m.p.116-118 ℃; MS m/e 402; IR (KBr) ν: 1650-3100,1608.2,1595.4,1512.0,1452.2,1395.6,1367.8,1346.1,1247.3,1204.0,1178.3,1133.4,1107.9,1048.6,1025.9,843.2,814.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.87-8.84 (1H, t, H-4); (8.26-8.24 1H, d, H-8); (7.64-7.61 1H, t, H-5); (7.60-7.56 2H, m, H-7, H-6); (7.56-7.47 1H, d, PhH); (7.38-7.34 1H, t, PhH); (7.06-7.02 2H, m, PhH); 4.54-4.49 (2H, m, COOCH ₂CH ₃); 4.03-3.99 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.90 (3H, s, OCH ₃); 1.54-1.44 (3H, t, COOCH ₂CH ₃); 1.42-1.24 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.92-0.83 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.71-0.61 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-benzyl-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester (400): take 1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester and cylite as raw material, pale yellow crystals, yield 81.2%, m.p.167-168 ℃; MS m/e 437; IR (KBr) ν: 1650-3050,1608.2,1511.8,1450.2,1396.9,1371.1,1347.9,1291.2,1275.6,1244.4,1178.5,1134.2,1108.8,1049.4,1029.7,849.6,816.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.91 (1H, s, H-4); (8.26-8.24 1H, d, H-8); (7.65-7.61 1H, t, H-5); (7.46-7.31 2H, m, H-7, H-6, PhH); (7.56-7.48 3H, m, PhH); (7.39-7.35 1H, t, PhH); (7.06-7.03 2H, m, PhH); 4.54-4.49 (2H, m, COOCH ₂CH ₃); 4.09-4.04 (2H, t, NCH ₂Ph); 3.84 (3H, s, OCH ₃); 1.49-1.45 (3H, t, COOCH ₂CH ₃) .1-(4-methoxyl group) phenyl-9-(4-luorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (401): take 1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester and 4-fluorine cylite as raw material, pale yellow crystals, yield 77.9%, m.p.146-148 ℃; MS m/e 454; IR (KBr) ν: 1650-3100,1611.4,1511.5,1457.2,1441.0,1392.3,1367.2,1290.5,1267.3,1251.7,1232.5,1196.5,1174.0,1106.6,1051.4,1023.8,827.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.90 (1H, s, H-4); (8.30-8.28 1H, d, H-8); (7.60-7.56 1H, t, H-5); (7.42-7.35 4H, m, H-7, H-6, PhH); (6.86-6.77 4H, m, PhH); (6.55-6.52 2H, m, PhH); 5.25 (2H, s, NCH ₂Ph); 4.54-4.49 (2H, m, COOCH ₂CH ₃); 3.85-3.80 (3H, s, OCH ₃); 1.49-1.42 (3H, t, COOCH ₂CH ₃).

9-benzyl-1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester (402): take 1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester and cylite as raw material, get white crystal, yield 46%, m.p.125-127 ℃; MS m/e 372; IR (KBr) ν: 1650-3100,1620.5,1581.0,1554.5,1457.8,1388.1,1496.1,1485.8,1341.5,1300.5,1256.0,1215.2,1176.2,1140.0,1059.0,792.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.77 (1H, s, H-4); (8.23-8.25 1H, d, H-8); (7.55-7.59 1H, d, H-5); (7.34-7.43 2H, d, H-6, H-7); (7.26-7.30 3H, m, PhH); (6.97-6.98 2H, d, PhH); 5.83 (2H, s, NCH ₂Ph); 4.47-4.53 (2H, m, COOCH ₂CH ₃); 3.58-3.63 (1H, m, CH (CH ₃) ₂); 1.47-1.51 (3H, t, COOCH ₂CH ₃); 1.37-1.38 (6H, d, CH (CH ₃) ₂).

9-ethyl-1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester (403): take 1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester and bromoethane as raw material, get white crystal, yield 70%, m.p.96-97 ℃; MS m/e 312; IR (KBr) ν: 1650-3100,1584.7,1555.1,1479.0,1445.7,1368.1,1341.5,1264.1,1245.5,1139.9,1078.3,1058.7,791.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.72 (1H, s, H-4); (8.19-8.21 1H, d, H-8); (7.61-7.65 1H, t, H-5); (7.51-7.53 1H, d, H-6); (7.33-7.36 1H, d, H-7); 4.62-4.67 (2H, m, COOCH ₂CH ₃); 4.47-4.52 (2H, m, NCH ₂CH ₃); 3.75-3.78 (1H, m, CH (CH ₃) ₂); 1.55-1.56 (6H, d, CH (CH ₃) ₂); 1.47-1.51 (6H, m, COOCH ₂CH ₃, NCH ₂CH ₃).

9-butyl-1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester (404): take 1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester and iodo-n-butane as raw material, obtain white crystal, yield 47%, m.p.100-102 ℃; MS m/e 340; IR (KBr) ν: 1650-3100,1581.4,1553.8,1468.8,1448.4,1365.9,1340.9,1263.2,1231.6,1110.0,1086.0,1062.3,895.4cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.72 (1H, s, H-4); (8.18-8.20 1H, d, H-8); (7.59-7.64 1H, t, H-5); (7.50-7.52 1H, d, H-6); (7.31-7.35 1H, t, H-7); 4.52-4.57 (2H, m, COOCH ₂CH ₃); 4.43-4.50 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 3.72-3.79 (1H, m, CH (CH ₃) ₂); 1.80-1.86 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.50-1.55 (6H, d, CH (CH ₃) ₂); 1.42-1.49 (5H, m, NCH ₂CH ₂CH ₂CH ₃, COOCH ₂CH ₃); 0.97-1.00 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-isopropyl-9-(3-chlorobenzyl)-B-carboline-3-carboxylic acid, ethyl ester (405): take 1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester and 3-chlorine cylite as raw material, get white crystal, yield 64%, m.p.125-127 ℃; MS m/e406; IR (KBr) ν: 1650-3050,1598.1,1579.8,1558.0,1473.1,1454.7,1436.1,1367.7,1339.0,1269.9,1236.7,1139.8,1091.8,1063.3,776.6cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.77 (1H, s, H-4); (8.24-8.26 1H, d, H-8); (7.57-7.61 1H, t, H-5); (7.37-7.40 2H, m, H-6, H-7); (7.18-7.26 2H, m, PhH); (7.03 1H, d, PhH); (6.80-6.82 1H, d, PhH); 5.80 (2H, s, NCH ₂Ph); 4.48-4.54 (2H, m, COOCH ₂CH ₃); 3.55-3.58 (1H, m, CH (CH ₃) ₂); 1.47-1.51 (3H, t, COOCH ₂CH ₃); 1.40-1.42 (6H, d, CH (CH ₃) ₂).

1-methyl-9-n-octyl-B-carboline-3-carboxylic acid, ethyl ester (406): take 1-methyl-B-carboline-3-carboxylic acid, ethyl ester and iodo normal octane as raw material, get white needle-like crystals, yield 67%, m.p.77.7-78.5 ℃; MS m/e 367; IR (KBr) ν: 1650-3100,1620.8,1579.5,1557.1,1392.6,1367.4,1252.3,1234.9,750.4cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.76 (1H, s, H-4); (8.19-8.17 1H, d, H-8); (7.64-7.60 1H, t, H-5); (7.51-7.49 1H, d, H-6); (7.36-7.32 1H, m, H-7); 4.58-4.50 (4H, m, COOCH ₂CH ₃, NCH ₂(CH ₂) ₆CH ₃); 3.13 (3H, s, CH ₃); 1.87-1.83 (2H, m, NCH ₂CH ₂(CH ₂) ₅CH ₃); 1.51-1.48 (3H, t, COOCH ₂CH ₃); 1.45-1.41 (2H, m, NCH ₂CH ₂CH ₂(CH ₂) ₄CH ₃); 1.35-1.25 (8H, m, NCH ₂CH ₂CH ₂(CH ₂) ₄CH ₃); 0.89-0.85 (3H, t, NCH ₂(CH ₂) ₆CH ₃).

Embodiment B-10:

1,9-two replaces the general synthesis technique (407-416) of B-carboline-3-carboxylic acid alcaloid-derivatives:

Get in the round-bottomed flask that 1,9-two replaces 500 milliliters of B-carbolines-3-carboxylic acid, ethyl ester (10mmol), add suitable quantity of water and ethanol and shake up and make as far as possible its dissolving, the sodium hydroxide (30mmol) that adds again adds zeolite, reflux.TLC monitoring reaction process was surveyed once every 30 minutes, after the raw material complete reaction, and stopped reaction.With the reactant liquor cooling, regulating pH value with dilute hydrochloric acid again is 6, filters, and with a large amount of water washings, obtains milky solid.Drying gets product.

9-ethyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid (407): take 9-ethyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get white solid, yield 87%, m.p.238-240 ℃; MS m/e 350; IR (KBr) ν: 1650-3100,1620.2,1598.1,1576.7,1555.6,1488.5,1455.7,1409.7,1391.4,1345.0,1315.2,1280.5,1254.1,1156.1,1134.2,1046.4,1015.9,953.4,837.5,794.5,778.0,743.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.95 (1H, s, H-4); (8.27-8.25 1H, d, H-8); (7.71-7.67 1H, t, H-5); (7.57-7.52 5H, m, H-6, H-7, PhH); (7.44-7.41 1H, t, PhH); 4.13-4.08 (2H, m, NCH ₂CH ₃); 1.08-1.04 (3H, t, NCH ₂CH ₃).

9-butyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid (408): take 9-butyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get white solid, yield 90%, m.p.238-241 ℃; MS m/e379; IR (KBr) ν: 1650-3100,1619.8,1596.9,1581.6,1551.0,1490.1,1468.6,1417.1,1390.3,1354.9,1304.5,1266.1,1134.1,1046.1,1014.8,964.3,848.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.95 (1H, s, H-4); (8.27-8.25 1H, d, H-8); (7.71-7.66 1H, t, H-5); (7.57 3H, s, H-6, H-7, PhH); (7.53-7.51 2H, m, PhH); (7.42-7.40 1H, m, PhH); 4.07-4.03 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.43-1.36 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.96-0.87 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.71-0.67 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-benzyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid (409): take 9-benzyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get white solid, yield 87%, m.p.164-167 ℃; MS m/e412; IR (KBr) ν: 1650-3100,1617.9,1599.2,1550.9,1490.7,1448.6,1414.8,1386.3,1348.1,1301.7,1264.0,1202.7,1155.0,1129.3,1051.5,1014.5,828.6,788.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 9.00 (1H, s, H-4); (8.32-8.30 1H, d, H-8); (7.66-7.62 1H, t, H-5); (7.47-7.40 2H, m, H-7, H-6); (7.31-7.29 4H, m, PhH); (7.20-7.14 3H, t, PhH); (6.58-6.56 2H, d, PhH); 5.30-5.26 (2H, t, NCH ₂Ph).

9-(4-luorobenzyl)-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid (410): take 9-(4-luorobenzyl)-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, obtain white solid, yield 93%, m.p.184-187 ℃; MS m/e 429; IR (KBr) ν: 1650-3100,1611.4,1548.9,1510.7,1489.3,1447.0,1414.6,1341.8,1299.7,1262.8,1229.4,1198.8,1156.6,1129.4,1091.2,1050.7,1013.9,905.1,848.1,829.8,749.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 9.00 (1H, s, H-4); (8.32-8.30 1H, d, H-8); (7.67-7.63 1H, t, H-5); (7.48-7.44 1H, t, H-6); (7.42-7.40 1H, d, H-7); (7.36-7.28 4H, m, PhH); (6.87-6.83 2H, m, PhH); (6.53-6.50 2H, m, PhH); 5.28 (2H, m, NCH ₂Ph).

9-butyl-1-isopropyl-B-carboline-3-carboxylic acid (411): take 9-butyl-1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, obtain white solid, yield 79%, m.p.104-106 ℃; MS m/e 266; IR (KBr) ν: 1650-3150,1622.2,1583.2,1559.0,1459.1,1475.1,1366.1,1346.2,1201.7,1135.3,1084.6,754.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.80 (1H, s, H-4); (8.18-8.20 1H, d, H-8); (7.65-7.69 1H, t, H-5); (7.53-7.55 1H, d, H-6); (7.36-7.50 1H, t, H-7); 4.54-4.58 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.78-3.80 (1H, m, CH (CH ₃) ₂); 1.83-1.89 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.51-1.52 (6H, d, CH (CH ₃) ₂); 1.45-1.48 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.00-1.03 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-benzyl-1-isopropyl-B-carboline-3-carboxylic acid (412): take 9-benzyl-1-isopropyl-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get white solid, yield 34%, m.p.111-113 ℃; MS m/e 300; IR (KBr) ν: 1650-3100,1622.0,1597.6,1576.5,1558.7,1451.7,1427.5,1465.8,1373.5,1357.7,1341.9,1210.2,1129.5,1091.2,769.7cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.85 (1H, s, H-4); (8.23-8.25 1H, d, H-8); (7.60-7.64 1H, t, H-5); (7.39-7.47 2H, m, H-6, H-7); (7.26-7.33 3H, m, PhH); (6.98-7.00 2H, d, PhH); 5.85 (2H, s, NCH ₂Ph); 3.60-3.69 (1H, m, CH (CH ₃) ₂); 1.32-1.34 (6H, d, CH (CH ₃) ₂).

9-(3-chlorobenzyl)-1-isopropyl-B-carboline-3-carboxylic acid (413): take 9-(3-chlorobenzyl)-1-isopropyl-β-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get white crystal, yield 64%, m.p.125-127 ℃; MSm/e 406; IR (KBr) ν: 1650-3210,1622.0,1597.7,1558.8,1451.7,1465.9,1357.7,1342.2,1210.3,1188.6,1091.4,873.9,746.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.85 (1H, s, H-4); (8.23-8.25 1H, d, H-8); (7.62-7.66 1H, t, H-5); (7.41-7.44 2H, m, H-6, H-7); (7.21-7.28 2H, m, PhH); (7.06 1H, s, PhH); (6.81-6.83 1H, d, PhH); 5.81 (2H, s, NCH ₂Ph); 3.57-3.60 (1H, m, CH (CH ₃) ₂); 1.35-1.36 (6H, d, CH (CH ₃) ₂).

9-ethyl-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid (414): take 9-ethyl-1-(4-anisyl)-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get the white particulate crystal, yield 92.5%, m.p.196-198 ℃; MS m/e 346; IR (KBr) ν: 1650-3100,1608.8,1512.1,1486.9,1455.4,1358.5,1247.9,1228.7,1176.2,1131.2,1052.7,1025.6,1029.7,836.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.93 (1H, s, H-4); (8.27-8.25 1H, d, H-8); (7.69-7.65 1H, t, H-5); (7.56-7.51 3H, m, H-7, H-6, PhH); (7.43-7.39 1H, t, PhH); (7.11-7.09 2H, d, PhH); 4.15-4.10 (2H, m, NCH ₂CH ₃); 3.94 (3H, s, OCH ₃); 1.06-1.029 (3H, t, NCH ₂CH ₃).

9-butyl-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid (415): take 9-butyl-1-(4-anisyl)-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get the white particulate crystal, yield 92.5%, m.p.167-168 ℃; MS m/e 374; IR (KBr) ν: 1650-3100,1608.2,1511.8,1450.2,1396.9,1371.1,1347.9,1291.2,1275.6,1244.4,1178.5,1134.2,1049.4,1029.7,849.6,816.4,784.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.87-8.82 (1H, t, H-4); (8.26-8.24 1H, t, H-8); (7.65-7.61 1H, t, H-5); (7.61-7.57 2H, m, H-7, H-6); (7.56-7.48 1H, d, PhH); (7.39-7.35 1H, t, PhH); (7.06-7.03 2H, m, PhH); 4.54-4.49 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 4.54-4.49 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 3.90 (3H, s, OCH ₃); 1.49-1.45 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.02-0.99 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

9-(4-luorobenzyl)-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid (416): take 9-(4-luorobenzyl)-1-(4-methoxyl group) phenyl-B-carboline-3-carboxylic acid, ethyl ester and sodium hydroxide as raw material, get white needle-like crystals, yield 77.9%, m.p.146-148 ℃; MS m/e 454; IR (KBr) ν: 1650-3100,1611.4,1511.5,1457.2,1441.0,1392.3,1367.2,1290.5,1267.3,1251.7,1232.5,1196.5,1174.0,1106.6,1051.4,1023.8,827.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.90 (1H, s, H-4); (8.30-8.28 1H, d, H-8); (7.60-7.56 1H, t, H-5); (7.42-7.35 4H, m, H-7, H-6, PhH); (6.86-6.77 4H, m, PhH); (6.55-6.52 2H, m, PhH); 5.25 (2H, s, NCH ₂Ph); 3.85-3.80 (3H, s, OCH ₃).

Embodiment B-11:

1,9-two replaces the general synthesis technique (417-421) of B-carboline-3-benzyl carboxylate alcaloid-derivatives:

Get 1,9-two replacement-B-carbolines-3-carboxylic acid (10mmol) adds 60 milliliters DMF and shakes up and make as far as possible its dissolving in 100 milliliters round-bottomed flask, adds alkyl halide (10mmol) under ice bath again, add NaH (10mmol), magnetic agitation.TLC monitoring reaction process was surveyed once every 30 minutes, after the raw material complete reaction, and stopped reaction.Reactant liquor poured into use ethyl acetate extraction in the suitable quantity of water, extract with except emulsifying, adds an amount of ethanol and concentrated hydrochloric acid with saturated sodium chloride solution washing 2 times, leave standstill, be concentrated into driedly, add the proper amount of acetone crystallization, the cooling crystallize out, filter to get solid, use water dissolution, the sodium bicarbonate alkalization adds ethyl acetate extraction, extract adds anhydrous sodium sulfate drying, activated carbon decolorizing is placed and after about 5-10 hour extract is crossed silica gel G and remove impurity, has been concentrated into a small amount of crystal and has separated out, cold preservation was placed 3-5 hour, crystallize out filters, washing, drying namely gets product.

9-butyl-1-(4-chlorphenyl)-B-carboline-3-benzyl carboxylate (417): take 9-butyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid and cylite as raw material, get white crystal, yield 73%, m.p.108-109 ℃; MS m/e 468; IR (KBr) ν: 1650-3100,1619.5,1596.4,1554.4,1490.0,1461.5,1377.6,1349.2,1302.0,1254.2,1218.8,1156.8,1134.2,1111.0,1087.3,1048.3,1014,951.1,932.5,900.9,827.8,788.0,749.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.88 (1H, s, H-4); (8.24-8.22 1H, d, H-8); (7.66-7.62 1H, t, H-5); (7.61-7.58 2H, m, H-6, H-7); (7.55-7.52 2H, m, PhH); (7.52-7.48 3H, m, PhH); (7.42-7.32 4H, m, PhH); 5.51 (2H, s, COOCH ₂Ph); 4.01-3.97 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.40-1.32 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.99-0.84 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.69-0.65 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-(4-chlorphenyl)-9-(4-luorobenzyl)-B-carboline-3-benzyl carboxylate (418): take 1-(4-chlorphenyl)-9-(4-luorobenzyl)-B-carboline-3-carboxylic acid and cylite as raw material, get white crystal, yield 57%, m.p.120-121 ℃; MSm/e520; IR (KBr) ν: 1650-3050,1620.0,1600.8,1553.9,1509.2,1491.3,1456.4,1436.8,1382.0,1345.0,1289.3,1266.1,1233.9,1155.8,1110.0,1090.3,1050.3,1013.2,991.4,955.3,905.5,874.7,825.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.92 (1H, s, H-4); (8.28-8.26 1H, d, H-8); (7.62-7.58 1H, t, H-5); (7.54-7.52 2H, d, H-6, H-7); (7.42-7.26 9H, m, PhH); (6.84-6.79 2H, m, PhH); (6.51-6.47 2H, t, PhH); 5.50 (2H, s, COOCH ₂Ph); 5.22 (2H, s, NCH ₂Ph).

1-methyl-9-(2,3,4,5, the 6-PFBBR)-B-carboline-3-benzyl carboxylate (419): with 1-methyl-9-(2,3,4,5, the 6-PFBBR)-B-carboline-3-carboxylic acid and cylite are raw material, get white crystal, yield 70%, m.p.184-186 ℃; MS m/e 407; IR (KBr) ν: 1650-3100,1621.7,1580.6,1557.6,1452.8,1383.3,1298.3,1345.1,1288.9,1237.0,1134.3,1077.3,1055.9,995.1,969.6,930.9,887.1,750.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.77 (1H, s, H-4); (8.19-8.17 1H, d, H-8); (7.60-7.56 3H, m, H-5, H-6, H-7); (7.43-7.35 5H, m, PhH); 5.97 (2H, m, COOCH ₂Ph); 5.53 (2H, s, NCH ₂Ph); 3.25 (3H, s, CH ₃).

1-methyl-9-benzyl-B-carboline-3-benzyl carboxylate (420): take 1-methyl-9-benzyl-B-carboline-3-carboxylic acid and cylite as raw material, get white crystal, yield 70%, m.p148-150 ℃; MS m/e 407; IR (KBr) ν: 1650-3100,1621.7,1580.6,1557.6,1452.5,1383.3,1298.3,1345.1,1288.9,1237.0,1134.3,1077.3,1055.0,995.1,969.6,930.9,887.1,750.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.80 (1H, s, H-4); (8.21-8.19 1H, d, H-8); (7.58-7.53 2H, m, H-5, H-6, H-7); (7.42-7.32 4H, m, PhH); (7.29-7.23 3H, m, PhH); (6.96-6.94 3H, m, PhH); 5.84 (2H, s, COOCH ₂Ph); 5.51 (2H, s, NCH ₂Ph); 2.96 (3H, s, CH ₃).

1-methyl-9-butyl-B-carboline-3-benzyl carboxylate (421): take 1-methyl-9-butyl-B-carboline-3-carboxylic acid and cylite as raw material, get white crystal, yield 86%, m.p.212-214 ℃; MS m/e 406; IR (KBr) ν: 1650-3100,1621.7,1578.9,1556.9,1456.3,1377.2,1343.9,1302.8,1258.9,1229.3,1204.5,1133.5,1062.5,994.2,968.9,923.8,891.6,784.8,748.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.75 (1H, s, H-4); (8.18-8.15 1H, m, H-8); (7.64-7.60 1H, m, H-5); (7.55-7.49 2H, t, H-6, H-7); (7.43-7.40 2H, m, PhH); (7.35-7.33 1H, m, PhH); (7.32-7.30 2H, m, PhH); 5.47 (2H, s, COOCH ₂Ph); 4.46-4.55 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.14 (3H, s, CH ₃); 1.88-1.80 (2H, m, NCH ₂CH ₂CH ₂CH ₃);

1.48-1.42(2H,m,NCH ₂CH ₂CH ₂CH ₃);1.00-0.97(3H,t,NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-12:

1,9-two replaces the general synthesis technique (422-424) of B-carboline-3-benzyl carboxylate alcaloid-derivatives:

Get 1,9-, two replacement-B-carbolines-3-carboxylic acid (10mmol) in 100 milliliters round-bottomed flask, add drying tube, adding 60 milliliters DMF shakes up and makes as far as possible its dissolving, under ice bath, add again alkyl halide (10mmol), add NaH (10mmol), magnetic agitation.TLC monitoring reaction process was surveyed once every 30 minutes, after the raw material complete reaction, and stopped reaction.Reactant liquor poured into use ethyl acetate extraction in the suitable quantity of water, extract with except emulsifying, adds an amount of ethanol and concentrated hydrochloric acid with saturated sodium chloride solution washing 2 times, leave standstill, be concentrated into driedly, add the proper amount of acetone crystallization, the cooling crystallize out, filter to get solid, use water dissolution, the sodium bicarbonate alkalization adds ethyl acetate extraction, extract adds anhydrous sodium sulfate drying, activated carbon decolorizing is placed and after about 5-10 hour extract is crossed silica gel G and remove impurity, has been concentrated into a small amount of crystal and has separated out, cold preservation was placed 3-5 hour, crystallize out filters, washing, drying namely gets product.

3-chlorobenzyl 1-(4-chlorphenyl)-9-butyl-B-carboline-3-carboxylate (422)

Take 9-butyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid and 3-chlorine cylite as raw material, get white crystal, yield 73%, m.p.108-109 ℃; MS m/e 468; IR (KBr) ν: 1650-3100,1619.5,1596.4,1554.4,1490.0,1461.5,1377.6,1349.2,1302.0,1254.2,1218.8,1156.8,1134.2,1111.0,1087.3,1048.3,1014.0,951.1,932.5,900.9,827.8,788.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.89 (1H, s, H-4); (8.24-8.22 1H, d, H-8); (7.66-7.62 1H, t, H-5); (7.61-7.58 2H, m, H-6, H-7); (7.55-7.52 2H, m, PhH); (7.52-7.48 2H, m, PhH); (7.42-7.32 4H, m, PhH); 5.51 (2H, s, COOCH ₂Ph); 4.01-3.97 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 1.40-1.32 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.99-0.84 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.69-0.65 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

3-chlorobenzyl 1-(4-chlorphenyl)-9-benzyl-B-carboline-3-carboxylate (423)

Take 9-benzyl-1-(4-chlorphenyl)-B-carboline-3-carboxylic acid and 3-chlorine cylite as raw material, get white crystal, yield 71%, m.p.184-186 ℃; MS m/e 468; IR (KBr) ν: 1650-3100,1619.5,1596.4,1554.4,1490.0,1461.5,1377.6,1349.2,1302.0,1254.2,1218.8,1156.8,1134.2,1111.0,1087.3,1048.3,1014.0,951.1,932.5,900.9,827.8,788.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.96 (1H, s, H-4); (8.31-8.29 1H, d, H-8); (7.63-7.59 1H, m, H-5); (7.54-7.53 1H, d, H-6); (7.44-7.39 3H, m, H-7, PhH); (7.35-7.31 4H, m, PhH); (7.27-7.27 1H, m, PhH); (7.20-7.12 3H, m, PhH); (6.56-6.54 2H, d, PhH); 5.48 (2H, s, COOCH ₂Ph); 5.27 (2H, s, NCH ₂Ph).

3-chlorobenzyl 9-butyl-1-methyl-B-carboline-3-carboxylate (424) gets white crystal, yield 66%, m.p.93-95 ℃ take 1-methyl-9-butyl-B-carboline-3-carboxylic acid and 3-chlorine cylite as raw material; MS m/e 406; IR (KBr) ν: 1650-3100,1621.7,1578.9,1556.9,1456.0,1377.2,1343.9,1302.8,1258.9,1229.3,1204.5,1133.5,1062.5,994.2,968.9,923.8,891.6,784.8,748.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.75 (1H, s, H-4); (8.18-8.15 1H, m, H-8); (7.64-7.60 1H, m, H-5); (7.55-7.49 2H, m, H-6, H-7); (7.43-7.40 1H, m, PhH); (7.35-7.33 1H, m, PhH); (7.35-7.33 1H, m, PhH); (7.31-7.31 1H, m, PhH); 5.47 (2H, s, COOCH ₂Ph); 4.46-4.55 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.14 (3H, s, CH ₃); 1.88-1.80 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.48-1.42 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.00-0.97 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-13:

1,9-two replaces the general synthesis technique (425-426) of B-carboline-3-butyl carboxylate alcaloid-derivatives:

1-(4-chlorphenyl)-9-(4 luorobenzyl)-B-carboline-3-butyl carboxylate (425): take 1-(4-chlorphenyl)-9-(4 luorobenzyl)-B-carboline-3-carboxylic acid and iodo-n-butane as raw material, get white crystal, yield 70%, m.p.117-119 ℃; IR (KBr) ν: 1650-3100,1622.1,1601.0,1554.5,1510.1,1491.6,1457.1,1387.3,1347.0,1298.1,1270.7,1232.3,1156.6,1115.9,1089.8,1058.7,1015.0,997.1,944.0,926.6,834.5,786.6cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.90 (1H, s, H-4); (8.31-8.29 1H, d, H-8); (7.62-7.59 1H, t, H-5); (7.43-7.37 2H, m, H-6, H-7); (7.33-7.25 3H, m, PhH); (6.84-6.80 3H, m, PhH); (6.51-6.48 2H, m, PhH); 5.23 (2H, s, NCH ₂Ph); 4.47-4.43 (2H, t, COOCH ₂CH ₂CH ₂CH ₃); 1.85-1.82 (2H, m, COOCH ₂CH ₂CH ₂CH ₃); 1.53-1.47 (2H, m, COOCH ₂CH ₂CH ₂CH ₃); 0.88-0.85 (3H, t, COOCH ₂CH ₂CH ₂CH ₃).

1-methyl-9-benzyl-B-carboline-3-butyl carboxylate (426): take 1-methyl-9-benzyl-B-carboline-3-carboxylic acid and iodo-n-butane as raw material, get white crystal, yield 75%, m.p.105-107 ℃; MS m/e 372; IR (KBr) ν: 1650-3100,1617.9,1589.0,1449.5,1395.1,1358.2,1337.1,1275.2,1237.2,1203.6,1058.2,997.5,971.6,950.0,911.7,828.5,785.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.86 (1H, s, H-4); (8.31-8.29 1H, d, H-8); (7.27-7.68 1H, m, H-5); (7.54-7.52 1H, d, H-6); (7.49-7.45 1H, t, H-7); (7.30-7.27 3H, m, PhH); (6.94-6.93 2H, m, PhH); 5.92 (2H, s, NCH ₂Ph); 4.53-4.50 (2H, t, COOCH ₂CH ₂CH ₂CH ₃); 3.30 (3H, s, CH ₃); 1.94-1.87 (2H, m, COOCH ₂CH ₂CH ₂CH ₃); 1.55-1.46 (2H, m, COOCH ₂CH ₂CH ₂CH ₃); 1.02-0.96 (3H, t, COOCH ₂CH ₂CH ₂CH ₃).

Embodiment B-14:

1-methyl-9-benzyl-3-[(2,3,4,5,6-, five fluorine) benzyloxy] synthesis technique of carbonyl-B-carboline (427):

Get 1-methyl-9-benzyl-B-carboline-3-carboxylic acid (10mmol) in 100 milliliters round-bottomed flask, add drying tube, adding 60 milliliters DMF shakes up and makes as far as possible its dissolving, under ice bath, add again 2,3,4,5,6-five fluorine cylites (10mmol) add NaH (10mmol), magnetic agitation.TLC monitoring reaction process was surveyed once every 30 minutes, after the raw material complete reaction, and stopped reaction.Reactant liquor poured into use ethyl acetate extraction in the suitable quantity of water, extract with except emulsifying, adds an amount of ethanol and concentrated hydrochloric acid with saturated sodium chloride solution washing 2 times, leave standstill, be concentrated into driedly, add the proper amount of acetone crystallization, the cooling crystallize out, filter to get solid, use water dissolution, the sodium bicarbonate alkalization, add ethyl acetate extraction, extract adds anhydrous sodium sulfate drying, and activated carbon decolorizing is placed and after about 5-10 hour extract crossed silica gel G and remove impurity, being concentrated into a small amount of crystal separates out, cold preservation was placed 3-5 hour, and crystallize out filters, washing, drying gets white crystal, yield 62%; M.p.146-148 ℃; MS m/e496; IR (KBr) ν: 1650-3100,1623.3,1507.9,1389.3,1346.0,1302.5,1285.5,1230.4,1210.4,1160.9,1137.5,1052.4,1005.7,958.2,935.9,748.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.75-8.70 (1H, s, H-4); (8.23-8.21 1H, d, H-8); (7.60-7.56 1H, t, H-5); (7.43-7.41 1H, d, H-6); (7.39-7.35 1H, t, H-7); (7.28-7.24 3H, m, PhH); (6.95-6.93 2H, m, PhH); 5.91-5.81 (2H, m, COOCH ₂Ph); 5.26-5.52 (2H, m, NCH ₂Ph); 3.01-2.88 (3H, s, CH ₃).

Embodiment B-15:

9-replaces the general synthesis technique of Yageine derivates (428-429):

Get the 10mmol yageine and be dissolved in DMF and the oxolane, wait dissolving rear adding 12mmol sodium hydride, then add halogenated alkane.React completely and fall back, use ethyl acetate extraction.Merge organic facies, washing, the saturated salt washing, silica gel G is crossed in dry decolouring, and filtrate is concentrated into dried, and recrystallization namely obtains product.

1-methyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline (428): take yageine and 4-fluorine cylite as raw material, get the milky crystal, yield 73.6%, m.p.130-132 ℃; MS:m/e 321; IR (KBr) ν: 1650-3050,1619.6,1510.8,1451.9,1353.1,1256.9,1161.4,1043.3,832.9cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.31-8.32 (1H, d, H-5); (8.01-8.04 1H, d, H-3); (7.79-7.81 1H, d, H-4); (6.96-6.98 4H, m, H-8, H-6, PhH); (6.91-6.94 1H, m, PhH); (6.74-6.75 1H, m, PhH); (6.86-6.89 1H, m, PhH); 5.69 (2H, s, NCH ₂Ph); 3.86 (3H, s, OCH ₃); 2.86 (3H, s, CH ₃).

1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-B-carboline (429): take yageine and 3-chlorine cylite as raw material, get white crystal, yield 84.6%, m.p.99-101 ℃; MS:m/e 337; IR (KBr) ν: 1650-3100,1620.8,1499.0,1450.6,1343.2,1256.2,1171.5,1046.8,820.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.33-8.35 (1H, d, H-5); (8.04-8.06 1H, d, H-3); (7.82-7.83 1H, d, H-4); (7.21-7.27 2H, m, H-8, H-6); (7.07 1H, s, PhH); (6.93-6.96 1H, m, PhH); (6.85-6.87 1H, t, PhH); (6.74-6.75 1H, d, PhH); 5.72 (2H, s, NCH ₂Ph); 3.89 (3H, s, OCH ₃); 2.87 (3H, s, CH ₃).

Embodiment B-16:

2,9-two replaces the general synthesis technique of Yageine derivates (430-459):

9-replaces yageine (10mmol), adds an amount of ethyl acetate it is dissolved fully, adds corresponding halogenated alkane (15-30mmol), and reflux 1-8 hour, be cooled to room temperature, filter the solid of separating out.Solid washs with a small amount of ethyl acetate, subsequently solid is dissolved in the dehydrated alcohol, and reflux is to clarification, and filtered while hot is placed the refrigerator recrystallization, gets crystal.

1-methyl-9-ethyl-2-butyl-7-methoxyl group-B-carboline iodine salt (430): take 1-methyl-9-ethyl-7-methoxyl group-B-carboline and iodo-n-butane as raw material, get yellow crystals, yield 82.6%, mp:198-201 ℃; MSm/e 240; IR (KBr) ν: 1650-3050,1626.5,1579.2,1518.0,1462.4,1336.1,1252.5,1168.2,1134.9,1093.7,856.3cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.64-8.65 (1H, d, H-5); (8.20-8.21 1H, d, H-3); (8.07-8.09 1H, d, H-4); (7.00-7.03 1H, m, H-8); (6.93-6.93 1H, d, H-6); 4.84-4.87 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 4.70-4.73 (2H, t, NCH ₂CH ₃); 4.01 (3H, s, OCH ₃); 3.39 (3H, s, CH ₃); 1.94-1.98 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.51-1.63 (5H, m, NCH ₂CH ₂CH ₂CH ₃, NCH ₂CH ₃); 0.99-1.02 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-9-ethyl-7-methoxyl group-2-benzyl-B-carboline bromine salt (431): take 1-methyl-9-ethyl-7-methoxyl group-B-carboline and cylite as raw material, get yellow crystals, yield 91.2%, m.p.232-234 ℃; MS m/e240; IR (KBr) ν: 1650-3050,1621.8,1579.5,1516.9,1495.1,1452.7,1332.7,1258.0,1225.3,1135.9,1038.8,830.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.78-8.80 (1H, d, H-5); (8.62-8.64 1H, d, H-3); (8.39-8.42 1H, d, H-4); (7.37-7.45 4H, m, H-8, H-6, PhH); (7.10-7.22 3H, m, PhH); 6.05 (2H, s, NCH ₂Ph); 4.72-4.74 (2H, d, NCH ₂CH ₃); 4.00 (3H, s, CH ₃O); 3.11 (3H, s, CH ₃); 1.39-1.42 (3H, t, NCH ₂CH ₃).

1-methyl-2-butyl-7-methoxyl group-9-benzyl-B-carboline iodine salt (432): take 1-methyl-7-methoxyl group-9-benzyl-B-carboline and iodo-n-butane as raw material, get pale yellow crystals, yield 83.7%, m.p.231-233 ℃; MS m/e 302; IR (KBr) ν: 1650-3050,1620.0,1579.4,1510.1,1465.8,1328.8,1257.7,1163.4,1126.8,1073.8,834.9cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.62-8.63 (1H, d, H-5); (8.23-8.25 1H, t, H-3); (8.13-8.15 1H, d, H-4); (7.34-7.38 4H, m, H-8, H-6, PhH); (7.12-7.14 1H, d, PhH); (7.07-7.10 1H, m, PhH); (6.84-6.84 1H, d, PhH); 5.94 (2H, s, NCH ₂Ph); 4.73-4.77 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.92 (3H, s, CH ₃O); 3.16 (3H, s, CH ₃); 1.92 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.47-1.53 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.55-1.59 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-9-benzyl-2-(2,3,4,5, the 6-PFBBR)-B-carboline bromine salt (433): with 1-methyl-7-methoxyl group-9-benzyl-B-carboline and 2,3,4,5,6-five fluorine cylites are raw material, get yellow crystals, yield 81.9%, m.p.155-157 ℃; MS m/e 302; IR (KBr) ν: 1650-3050,1623.2,1580.9,1506.4,1466.2,1327.1,1256.9,1154.1,1123.9,1088.0,828.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 9.06 (1H, s, H-5); (8.22 1H, s, H-3); (8.13-8.15 1H, d, H-4); (7.34-7.38 4H, m, H-8, H-6, PhH); (7.12-7.14 1H, d, PhH); (7.07-7.10 1H, m, PhH); (6.84-6.84 1H, d, PhH); 5.94 (2H, s, NCH ₂Ph); 4.73-4.77 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.92 (3H, s, CH ₃O); 3.16 (3H, s, CH ₃); 1.92 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.47-1.53 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.55-1.59 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-2,9-diethyl-7-methoxyl group-B-carboline iodine salt (434): take 1-methyl-9-ethyl-7-methoxyl group-B-carboline and iodoethane as raw material, get pale yellow crystals, yield 73.8%, m.p.233-235 ℃; MS m/e240; IR (KBr) ν: 1650-3050,1624.1,1579.1,1511.8,1446.9,1332.1,1266.0,1227.5,1133.4,1035.1,820.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.70-8.71 (1H, d, H-5); (8.19-8.21 1H, d, H-3); (8.08-8.10 1H, d, H-4); (7.04-7.07 1H, m, H-8); (6.93-6.93 1H, d, H-6); 4.97-5.00 (2H, m, NCH ₂CH ₃); 4.68-4.73 (2H, m, NCH ₂CH ₃); 4.02 (3H, s, CH ₃O); 3.42 (3H, s, CH ₃); 1.67-1.71 (3H, t, NCH ₂CH ₃); 1.60-1.63 (3H, t, NCH ₂CH ₃).

1-methyl-9-ethyl-7-methoxyl group-2-(4-luorobenzyl)-B-carboline bromine salt (435): take 1-methyl-9-ethyl-7-methoxyl group-B-carboline and 4-fluorine cylite as raw material, get white crystal, yield 76.4%, m.p.161-163 ℃; MS m/e 240; IR (KBr) ν: 1650-3050,1624.0,1581.2,1510.3,1453.1,1330.2,1258.9,1225.9,1134.1,1038.0,822.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.80-8.82 (1H, d, H-5); (8.65-8.66 1H, d, H-3); (8.41-8.42 1H, d, H-4); (7.40-7.42 1H, d, H-8); (7.25-7.31 4H, m, H-6, PhH); (7.11-7.14 1H, m, PhH); 6.04 (2H, s, NCH ₂Ph); 4.74-4.76 (2H, d, NCH ₂CH ₃); 4.00 (3H, s, CH ₃O); 3.11 (3H, s, CH ₃); 1.39-1.43 (3H, t, NCH ₂CH ₃).

1-methyl-9-ethyl-7-methoxyl group-2-phenylpropyl-B-carboline bromine salt (436): take 1-methyl-9-ethyl-7-methoxyl group-B-carboline and 1-bromo-3-phenyl-propane as raw material, get the milky crystal, yield 84.2%, m.p.199-201 ℃; MS m/e 240; IR (KBr) ν: 1650-3150,1623.2,1577.8,1517.5,1453.5,1347.1,1268.1,1224.4,1134.9,1038.8,819.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.70-8.72 (1H, d, H-5); (8.17-8.19 1H, d, H-3); (8.03-8.05 1H, d, H-4); (7.33-7.37 3H, t, H-8, H-6, PhH); (7.27-7.28 2H, d, PhH); (6.98-7.01 1H, d, PhH); (6.59-6.60 1H, d, PhH); 4.90-4.96 (2H, t, NCH ₂CH ₂CH ₂Ph); 4.53-4.57 (2H, m, NCH ₂CH ₃); 3.86 (3H, s, CH ₃O); 3.16 (3H, s, CH ₃); 2.83-2.86 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.25-2.27 (2H, m, NCH ₂CH ₂CH ₂Ph); 1.63-1.74 (3H, t, NCH ₂CH ₃).

1-methyl-2-ethyl-7-methoxyl group-9-benzyl-B-carboline iodine salt (437): take 1-methyl-7-methoxyl group-9-benzyl-B-carboline and iodoethane as raw material, get pale yellow crystals, yield 74.8%, m.p.265-267 ℃; MS m/e302; IR (KBr) ν: 1650-3100,1625.0,1579.8,1518.6,1454.7,1324.7,1247.2,1162.8,1134.1,1070.9,816.1cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.70-8.72 (1H, d, H-5); (8.63-8.65 1H, t, H-3); (8.43-8.45 1H, d, H-4); (7.29-7.38 4H, m, H-8, H-6, PhH); (7.12-7.15 1H, m, PhH); (7.06-7.08 2H, d, PhH); 6.06 (2H, s, NCH ₂Ph); 4.68-4.70 (2H, m, NCH ₂CH ₃); 3.90 (3H, s, CH ₃O); 3.00 (3H, s, CH ₃); 1.44-1.48 (3H, t, NCH ₂CH ₃).

1-methyl-7-methoxyl group-9-benzyl-2-(4-luorobenzyl)-B-carboline bromine salt (438): take 1-methyl-7-methoxyl group-9-benzyl-B-carboline and 4-fluorine cylite as raw material, get the milky crystal, yield 79.4%, m.p.240-242 ℃; MS m/e 302; IR (KBr) ν: 1650-3050,1621.2,1580.3,1512.2,1463.5,1323.7,1256.6,1161.5,1139.4,1076.7,829.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.89-8.91 (1H, d, H-5); (8.27-8.29 1H, d, H-3); (8.15-8.18 1H, d, H-4); (7.32-7.37 3H, m, H-8, H-6, PhH); (7.22-7.25 2H, m, PhH); (7.06-7.10 3H, m, PhH); (7.00-7.02 2H, t, PhH); (6.80-6.80 1H, d, PhH); 6.24 (2H, s, NCH ₂Ph); 5.81 (2H, s, NCH ₂Ph); 3.91 (3H, s, CH ₃O); 3.04-3.10 (3H, s, CH ₃).

1-methyl-7-methoxyl group-9-benzyl-2-phenylpropyl-B-carboline bromine salt (439): take 1-methyl-7-methoxyl group-9-benzyl-B-carboline and 1-bromo-3-phenyl-propane as raw material, get the milky crystal, yield 83.2%, m.p.235-237 ℃; MS m/e 302; IR (KBr) ν: 1650-3050,1624.0,1581.5,1518.7,1464.2,1334.5,1260.6,1151.1,1138.0,1078.1,824.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.80-8.82 (1H, d, H-5); (8.63-8.65 1H, d, H-3); (8.39-8.41 1H, d, H-4); (7.38-7.45 3H, m, H-8, H-6, PhH); (7.10-7.36 9H, m, PhH); 6.05 (2H, s, NCH ₂Ph); 4.66-4.70 (2H, t, NCH ₂CH ₂CH ₂Ph); 3.97 (3H, s, CH ₃O); 2.97 (3H, s, CH ₃); 2.69-2.73 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.07-2.11 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-9-ethyl-7-methoxyl group-2-(3-chlorobenzyl)-B-carboline bromine salt (440): take 1-methyl-9-ethyl-7-methoxyl group-B-carboline and 3-chlorine cylite as raw material, get the milky crystal, yield 76.4%, m.p.220-222 ℃; MS m/e 241; IR (KBr) ν: 1650-3100,1623.5,1579.8,1519.0,1452.7,1329.5,1262.9,1226.2,1134.9,1039.2,821.9cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.80-8.81 (1H, d, H-5); (8.64-8.66 1H, d, H-3); (8.40-8.42 1H, d, H-4); (7.45-7.48 2H, m, H-8, H-6); (7.39-7.43 2H, m, PhH); (7.11-7.16 2H, m, PhH); 6.07 (2H, s, NCH ₂Ph); 4.74-4.76 (2H, m, NCH ₂CH ₃); 4.01 (3H, s, CH ₃O); 3.12 (3H, s, CH ₃); 1.40-1.44 (3H, t, NCH ₂CH ₃).

1-methyl-2-butyl-7-methoxyl group-9-phenylpropyl-B-carboline iodine salt (441): take 1-methyl-7-methoxyl group-9-phenylpropyl-B-carboline and iodo-n-butane as raw material, get yellow crystals, yield 83.4%, m.p.203-204 ℃; MS m/e 302; IR (KBr) ν: 1650-3050,1622.5,1577.9,1516.2,1459.6,1338.2,1245.7,1161.2,1126.6,1030.7,825.8cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.65-8.67 (1H, d, H-5); (8.18-8.19 1H, d, H-3); (8.03-8.05 1H, d, H-4); (7.33-7.37 2H, m, H-8, H-6); (7.24-7.28 3H, m, PhH); (6.97-7.00 1H, d, PhH); (6.60-6.60 1H, d, PhH); 4.81-4.85 (2H, t, NCH ₂CH ₂CH ₂Ph); 4.54-4.59 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.86 (3H, s, CH ₃O); 3.16 (3H, s, CH ₃); 2.83-2.87 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.22-2.30 (2H, m, NCH ₂CH ₂CH ₂Ph); 1.89-1.96 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.48-1.55 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.99-1.02 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-9-phenylpropyl-2-benzyl-B-carboline bromine salt (442): take 1-methyl-7-methoxyl group-9-phenylpropyl-B-carboline and cylite as raw material, get pale yellow crystals, yield 72.7%, m.p.226-227 ℃; MS m/e 330; IR (KBr) ν: 1650-3050,1622.4,1578.8,1515.3,1453.4,1348.0,1249.6,1154.2,1134.3,1031.5,823.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.84-8.85 (1H, d, H-5); (8.26-8.27 1H, d, H-3); (8.07-8.09 1H, d, H-4); (7.30-7.34 5H, m, H-8, H-6, PhH); (7.18-7.23 5H, m, PhH); (6.96-6.99 1H, d, PhH); (6.52-6.53 1H, d, PhH); 6.29 (2H, t, NCH ₂Ph); 4.43-4.47 (2H, t, NCH ₂CH ₂CH ₂Ph); 3.83 (3H, s, CH ₃O); 3.14 (3H, s, CH ₃); 2.76-2.79 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.17-2.21 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-7-methoxyl group-9-phenylpropyl-2-(4-luorobenzyl)-B-carboline bromine salt (443): take 1-methyl-7-methoxyl group-9-phenylpropyl-B-carboline and 4-fluorine cylite as raw material, get pale yellow crystals, yield 83.1%, m.p.189-190 ℃; MS m/e 330; IR (KBr) ν: 1650-3050,1624.7,1579.3,1511.4,1456.4,1347.9,1247.9,1156.2,1134.8,1032.9,823.9cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.93-8.94 (1H, d, H-5); (8.21-8.22 1H, d, H-3); (8.06-8.08 1H, d, H-4); (7.28-7.35 4H, m, H-8, H-6, PhH); (7.21-7.25 3H, m, PhH); (6.99-7.03 1H, m, PhH); (6.51-6.51 1H, d, PhH); 6.37 (2H, s, NCH ₂Ph); 4.42-4.46 (2H, t, NCH ₂CH ₂CH ₂Ph); 3.83 (3H, s, CH ₃O); 3.19 (3H, s, CH ₃); 2.77-2.80 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.22-2.27 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-2-ethyl-7-methoxyl group-9-phenylpropyl-B-carboline iodine salt (444): take 1-methyl-7-methoxyl group-9-phenylpropyl-B-carboline and iodoethane as raw material, get pale yellow crystals, yield 85.4%, m.p.207-209 ℃; MS m/e 330; IR (KBr) ν: 1650-3050,1624.1,1579.0,1514.8,1452.0,1338.0,1237.1,1162.8,1130.0,1032.8,823.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.71-8.72 (1H, d, H-5); (8.18-8.19 1H, d, H-3); (8.04-8.06 1H, d, H-4); (7.34-7.37 2H, m, H-8, H-6); (7.28 2H, s, PhH); (7.26 1H, s, PhH); (6.99-7.01 1H, d, PhH); (6.60-6.60 1H, d, PhH); 4.91-4.94 (2H, t, NCH ₂CH ₂CH ₂Ph); 4.54-4.58 (2H, t, NCH ₂CH ₃); 3.86 (3H, s, CH ₃O); 3.17 (3H, s, CH ₃); 2.84-2.87 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.25-2.29 (2H, m, NCH ₂CH ₂CH ₂Ph); 1.63-1.68 (3H, t, NCH ₂CH ₃).

1-methyl-7-methoxyl group-2,9-two phenylpropyl-B-carboline bromine salt (445): take 1-methyl-7-methoxyl group-9-phenylpropyl-B-carboline and 1-bromo-3-phenyl-propane as raw material, get white crystal, yield 84.7%, m.p.251-253 ℃; IR (KBr) ν: 1650-3100,1622.6,1576.4,1452.8,1345.5,1245.7,1152.2,1134.4,1031.1,824.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.61-8.63 (1H, d, H-5); (8.49-8.50 1H, d, H-3); (8.33-8.35 1H, d, H-4); (7.07-7.32 12H, m, H-8, H-6, PhH); 4.65-4.71 (4H, m, NCH ₂CH ₂CH ₂Ph); (3.94 3H, s, CH3O); 3.06 (3H, s, CH ₃); 2.73-2.77 (4H, m, NCH ₂CH ₂CH ₂Ph); 2.13-2.20 (4H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-2-butyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline iodine salt (446): take 1-methyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline and iodo-n-butane as raw material, get white crystal, yield 78.7%, m.p.224-225 ℃; MS m/e 320; IR (KBr) ν: 1650-3050,1622.9,1581.6,1511.1,1464.0,1349.7,1250.9,1161.5,1132.9,1032.9,821.7cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.68-8.70 (1H, d, H-5); (8.61-8.62 1H, d, H-3); (8.43-8.45 1H, d, H-4); (7.35-7.38 3H, m, H-8, H-6, PhH); (7.23 1H, s, PhH); (7.13-7.16 1H, m, PhH); (6.93-6.95 1H, d, PhH); 6.06 (2H, s, NCH ₂Ph); 4.63-4.67 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.91 (3H, s, CH ₃O); 2.98 (3H, s, CH ₃); 1.79-1.83 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.34-1.39 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.91-0.94 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-2-hexyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline iodine salt (447): take 1-methyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline and iodo normal hexane as raw material, get pale yellow crystals, yield 84.6%, m.p.212-214 ℃; MS m/e 320; IR (KBr) ν: 1650-3050,1622.6,1578.6,1510.7,1463.2,1375.8,1259.2,1159.3,1133.8,1032.1,822.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.56-8.58 (1H, d, H-5); (8.25-8.27 1H, d, H-3); (8.13-8.15 1H, d, H-4); (7.12-7.26 2H, m, H-8, H-6); (7.03-7.07 3H, m, PhH); (6.82-6.82 1H, d, PhH); 5.97 (2H, s, NCH ₂Ph); 4.66-4.70 (2H, t, NCH ₂CH ₂CH ₂CH ₂CH ₂CH ₃); 3.91 (3H, s, CH ₃O); 3.16 (3H, s, CH ₃); 1.91-1.94 (2H, m, NCH ₂CH ₂(CH ₂) ₃CH ₃); 1.43-1.47 (2H, m, N (CH ₂) ₂CH ₂(CH ₂) ₂CH ₃); 1.26-1.30 (4H, m, N (CH ₂) ₃CH ₂CH ₂CH ₃); 0.84-0.88 (3H, t, N (CH ₂) ₅CH ₃).

1-methyl-7-methoxyl group-9-(4-luorobenzyl)-2-benzyl-B-carboline bromine salt (448): take 1-methyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline and cylite as raw material, get white crystal, yield 84.2%, m.p.248-250 ℃; MS m/e 320; IR (KBr) ν: 1650-3050,1625.5,1579.9,1511.4,1461.8,1324.9,1256.1,1158.9,1138.3,1077.4,825.3cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.86-8.87 (1H, d, H-5); (8.72-8.73 1H, d, H-3); (8.47-8.49 1H, d, H-4); (7.34-7.42 4H, m, H-8, H-6, PhH); (7.11-7.17 5H, m, PhH); (7.01-7.05 2H, m, PhH); 6.00-6.01 (4H, d, NCH ₂Ph); 3.91 (3H, s, CH ₃O); 2.84 (3H, s, CH ₃).

1-methyl-7-methoxyl group-2,9-two (4-luorobenzyl)-B-carboline bromine salt (449): take 1-methyl-7-methoxyl group-9-(4-luorobenzyl)-B-carboline and 4-fluorine cylite as raw material, get white crystal, yield 92.6%, m.p.225-227 ℃; MS m/e 320; IR (KBr) ν: 1650-3050,1622.1,1581.5,1511.6,1462.0,1324.1,1256.5,1160.8,1139.7,1078.3,823.0cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.90-8.91 (1H, d, H-5); (8.28-8.29 1H, d, H-3); (8.16-8.18 1H, d, H-4); (7.28 1H, s, H-8); (7.25-7.26 1H, d, H-6); (6.97-7.09 7H, m, PhH); (6.77-6.78 1H, d, PhH); 6.22 (2H, s, NCH ₂Ph); 5.81 (2H, s, NCH ₂Ph); 3.91-3.93 (3H, s, CH ₃O); 3.12 (3H, s, CH ₃).

1-methyl-2-butyl-7-methoxyl group-9-(3-chlorobenzyl)-B-carboline iodine salt (450): take 1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-B-carboline and iodo-n-butane as raw material, get pale yellow crystals, yield 78.4%, m.p.228-229 ℃; MS m/e 336; IR (KBr) ν: 1650-3050,1622.9,1577.5,1515.3,1462.4,1349.0,1252.7,1165.9,1133.5,1034.9,825.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.54-8.56 (1H, d, H-5); (8.22-8.24 1H, d, H-3); (8.13-8.15 1H, d, H-4); (7.33-7.34 2H, d, H-8, H-6); (7.14-7.16 1H, d, PhH); (7.07-7.10 2H, t, PhH); (6.80-6.81 1H, d, PhH); 5.98 (2H, s, NCH ₂Ph); 4.69-4.73 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.92 (3H, s, CH ₃O); 3.18 (3H, s, CH ₃); 1.93 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.47-1.53 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.97-1.01 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-2-benzyl-B-carboline bromine salt (451): take 1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-B-carboline and cylite as raw material, get pale yellow crystals, yield 82.3%, m.p.259-260 ℃; MS m/e 336; IR (KBr) ν: 1650-3050,1621.2,1576.6,1518.0,1461.3,1349.8,1255.6,1160.1,1139.6,1077.3,832.6cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.86-8.88 (1H, d, H-5); (8.73-8.74 1H, d, H-3); (8.48-8.50 1H, d, H-4); (7.31-7.42 6H, m, H-8, H-6, PhH); (7.12-7.18 4H, m, PhH); (6.87-6.89 1H, d, PhH); 6.00-6.04 (4H, d, NCH ₂Ph); 3.91 (3H, s, CH ₃O); 2.83 (3H, s, CH ₃).

1-methyl-7-methoxyl group-2,9-two (3-chlorobenzyl)-B-carboline bromine salt (452): take 1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-B-carboline and 3-chlorine cylite as raw material, get yellow crystals, yield 86.7%, m.p. 267-269 ℃; MS m/e 336; IR (KBr) ν: 1650-3050,1624.8,1577.0,1518.3,1456.6,1327.0,1258.6,1162.9,1135.3,1082.6,824.6cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.85-8.86 (1H, d, H-5); (8.72-8.74 1H, d, H-3); (8.48-8.50 1H, d, H-4); (7.31-7.45 6H, m, H-8, H-6, PhH); (7.16-7.19 2H, m, PhH); (7.07-7.09 1H, d, PhH); (6.89-6.91 1H, d, PhH); 6.00-6.04 (4H, d, NCH ₂Ph); 3.91 (3H, s, CH ₃O); 2.83 (3H, s, CH ₃).

1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-2-phenylpropyl-B-carboline bromine salt (453): take 1-methyl-7-methoxyl group-9-(3-chlorobenzyl)-B-carboline and 1-bromo-3-phenyl-propane as raw material, get light grey crystal, yield 82.4%, m.p.228-230 ℃; MS m/e 336; IR (KBr) ν: 1650-3050,1622.7,1574.9,1465.2,1346.8,1258.7,1156.9,1138.8,1030.6,819.8cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.78-8.80 (1H, d, H-5); (8.62-8.63 1H, d, H-3); (8.38-8.41 1H, d, H-4); (7.10-7.29 11H, m, H-8, H-6, PhH); 6.01 (2H, s, NCH ₂Ph); 4.66-4.70 (2H, t, NCH ₂CH ₂CH ₂Ph); 3.96 (3H, s, CH ₃O); 2.98 (3H, s, CH ₃); 2.70-2.73 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.08-2.12 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-7-methoxyl group-9-butyl-2-(2,3,4,5, the 6-PFBBR)-B-carboline bromine salt (454): with 1-methyl-7-methoxyl group-9-butyl-B-carboline and 2,3,4,5,6-five fluorine cylites are raw material, get pale yellow crystals, yield 78%, m.p.172-174 ℃; MS m/e 269; IR (KBr) ν: 3010.0,2963.4,2874.2,1657.9,1580.3,1525.1,1463.9,1349.1,1249.8,1215.1,1167.9,1134.7,1021.6,817.5cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 9.05-9.06 (1H, d, H-5), 8.31-8.33 (1H, d, H-3), 8.15-8.17 (1H, d, H-4), 6.99-7.02 (1H, d, H-8), 6.88 (1H, s, H-6), 6.60 (2H, s, NCH ₂Ph), 4.50-4.54 (2H, t, NCH ₂CH ₂CH ₂CH ₃), 4.00 (3H, s, CH ₃O), 3.36 (3H, s, CH ₃), 1.86-2.03 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 1.44-1.50 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 0.98-1.02 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-9-butyl-2-(3-chlorobenzyl)-B-carboline bromine salt (455): take 1-methyl-7-methoxyl group-9-butyl-B-carboline and 3-chlorine cylite as raw material, get pale yellow crystals, yield 72%, m.p.241-243 ℃; MS m/e 270; IR (KBr) ν: 3009.4,2949.7,2868.7,1621.1,1514.2,1467.5,1349.5,1248.0,1210.8,1164.9,1140.0,1033.9,832.9cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 9.06-9.07 (1H, d, H-5), (8.28-8.29 1H, d, H-3), 8.13-8.15 (1H, d, H-4), 7.23-7.27 (3H, m, H-8, H-6, PhH), 7.03-7.08 (2H, m, PhH), 6.86 (1H, s, PhH), 6.50 (2H, s, NCH ₂Ph), 4.44-4.48 (2H, t, NCH ₂CH ₂CH ₂CH ₃), 4.00 (3H, s, CH ₃O), 3.29 (3H, s, CH ₃), 1.84-1.87 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 1.41-1.47 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 0.96-1.00 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-9-butyl-2-phenylpropyl-B-carboline bromine salt (456): take 1-methyl-7-methoxyl group-9-butyl-B-carboline and 1-bromo-3-phenyl-propane as raw material, get pale yellow crystals, yield 79%, m.p.195-197 ℃; MS m/e 269; IR (KBr) ν: 2998.5,2957.7,1625.0,1518.6,1454.7,1348.3,1247.2,1208.4,1162.8,1134.1,1034.9,933.8,816.1cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.90-8.92 (1H, d, H-5), (8.19-8.20 1H, d, H-3), 8.07-8.09 (1H, d, H-4), 7.18 – 7.31 (5H, m, H-8, H-6, PhH), 7.00-7.03 (1H, d, PhH), 6.88 (1H, s, PhH), 4.97-5.01 (2H, t, NCH ₃CH ₂CH ₂CH ₃), 4.51-455 (2H, t, NCH ₂CH ₂CH ₂Ph), 3.99 (3H, s, CH ₃O), 3.20 (3H, s, CH ₃), 2.81-2.91 (2H, t, NCH ₂CH ₂CH ₂Ph), 2.30-2.33 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 1.83-1.87 (2H, m, NCH ₂CH ₂CH ₂Ph), 1.44-1.50 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 0.99-1.03 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-2,9-dibutyl-B-carboline iodine salt (457): take 1-methyl-7-methoxyl group-9-butyl-B-carboline and iodo-n-butane as raw material, get pale yellow crystals, yield 83%, m.p.200-203 ℃; MSm/e 269; IR (KBr) ν: 2998.7,2958.1,2931.8,1624.8,1514.1,1454.2,1345.7,1245.9,1210.8,1170.3,1139.4,1035.4,817.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.72-8.74 (1H, d, H-5), 8.24-8.26 (1H, d, H-3), 8.08-8.11 (1H, d, H-4), 6.99-7.02 (1H, d, H-8), 6.92 (1H, s, H-6), 4.85-4.89 (2H, t, NCH ₂CH ₂CH ₂CH ₃), 4.58-4.62 (2H, t, NCH ₂CH ₂CH ₂CH ₃), 4.01 (3H, s, CH ₃O), 3.36 (3H, s, CH ₃), 1.85-1.99 (4H, m, NCH ₂CH ₂CH ₂CH ₃), 1.45-1.58 (4H, m, NCH ₂CH ₂CH ₂CH ₃), 0.94-1.03 (6H, m, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-2-ethyl-9-butyl-B-carboline iodine salt (458): take 1-methyl-7-methoxyl group-9-butyl-B-carboline and iodoethane as raw material, get pale yellow crystals, yield 73.3%, m.p.216-218 ℃; MSm/e 269; IR (KBr) ν: 3009.4,2957.5,2929.6,1621.1,1515.9,1460.5,1350.0,1246.8,1205.8,1173.8,1133.8,1033.3,1016.7,820.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.76-8.78 (1H, d, H-5), 8.23-8.25 (1H, d, H-3), 8.08-8.11 (1H, d, H-4), 7.01-7.03 (1H, d, H-8), 6.92 (1H, s, H-6), 4.97-4.99 (2H, m, NCH ₂CH ₃), 4.57-4.61 (2H, t, NCH ₂CH ₂CH ₂CH ₃), 4.01 (3H, s, CH ₃O), 3.38 (3H, s, CH ₃), 1.88-1.92 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 1.65-1.69 (3H, t, NCH ₂CH ₃), 1.47-1.53 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 1.00-1.04 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-methoxyl group-9-butyl-2-benzyl-B-carboline bromine salt (459): take 1-methyl-7-methoxyl group-9-butyl-B-carboline and cylite as raw material, get pale yellow crystals, yield 75%, m.p.239-241 ℃; MS m/e269; IR (KBr) ν: 3038.7,2931.7,2850,1621.8,1513.9,1451.0,1342.9,1248.0,1207.8,1163.6,1137.1,1032.1,831.9cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) 9.01-9.02 (1H, d, H-5), 8.36-8.38 (1H, d, H-3), 8.14-8.16 (1H, d, H-4), 7.34-7.37 (4H, m, H-8, H-6, PhH), 7.10-7.13 (2H, m, PhH), 6.97 (1H, s, PhH), 6.35 (2H, s, NCH ₂Ph), 4.52-4.56 (2H, t, NCH ₂CH ₂CH ₂CH ₃), 3.99 (3H, s, CH ₃O), 3.18 (3H, s, CH ₃), 1.82-1.85 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 1.39-1.44 (2H, m, NCH ₂CH ₂CH ₂CH ₃), 0.97-1.01 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-17:

7,9-two replaces the general synthesis technique of Yageine derivates (460-462):

Get 1-methyl-7-hydroxyl-9-replacement beta-carboline derivatives (10mmol) and place round-bottomed flask, add DMF; Wait dissolving rear adding 12mmol sodium hydride, then add corresponding halogenated alkane (12mmol).(general response time 30min) pours reactant liquor in the 50ml water into after the raw material complete reaction, is extracted in the water with ethyl acetate (400ml, minute four extractions) to have (with the TLC monitoring, existing without product point onboard) without product.Organic facies with the washing of 200ml washing twice, 100ml saturated sodium-chloride once added anhydrous sodium sulfate drying 5 hours, the filtering desiccant is concentrated into extract dried, adds the 40ml dehydrated alcohol, it is an amount of to add concentrated hydrochloric acid, and solid is dissolved fully, transfers pH2-3, be concentrated into a small amount of liquid of residue, add a small amount of acetone, cold preservation is more than 10 hours, filter, solid washes twice with petroleum ether, and solid is poured in the 50ml water, add sodium bicarbonate and transfer about pH8, divide four extractions, organic addition anhydrous sodium sulfate drying with the 200ml ethyl acetate, add activated carbon decolorizing, leave standstill about 5 hours, cross silica gel G, use the ethyl acetate rinse silica gel G, liquid under waiting to filter exists without product, stop flushing, filtrate is concentrated into dried, add the petroleum ether recrystallization, cold preservation was treated crystallization about 10 hours, filter, with the petroleum ether flushing, obtain chemical compound.

1-methyl-7-(3-chlorine benzyloxy)-9-phenylpropyl-B-carboline (460): take 1-methyl-7-hydroxyl-9-phenylpropyl-B-carboline and 3-chlorine cylite as raw material, get white crystal, yield 75.9%, m.p.127-128 ℃; IR (KBr) ν: 1650-3000,1622.8,1494.0,1455.9,1346.5,1250.2,1163.2,1030.2,823.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.27-8.28 (1H, d, H-5); (7.96-7.99 1H, d, H-3); (7.74-7.76 1H, d, H-4); (7.49 1H, s, H-8); (7.20-7.35 8H, m, H-6, PhH); (6.93-6.96 1H, d, PhH); (6.68-6.69 1H, d, PhH); 5.05 (2H, s, NCH ₂Ph); 4.42-4.46 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.91 (3H, s, CH ₃); 2.72-2.76 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.11-2.15 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-7-(4-fluorine benzyloxy)-9-phenylpropyl-B-carboline (461): take 1-methyl-7-hydroxyl-9-phenylpropyl-B-carboline and 4-fluorine cylite as raw material, get white crystal, yield 69.4%, m.p.158-159 ℃; IR (KBr) ν: 1650-3100,1620.3,1493.7,1448.0,1344.0,1226.1,1159.2,1034.4,815.8cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.27-8.28 (1H, d, H-5); (7.97-7.99 1H, d, H-3); (7.75-7.76 1H, d, H-4); (7.44-7.47 2H, m, H-8, H-6); (7.31-7.38 2H, m, PhH); (7.08-7.25 5H, m, PhH); (6.93-6.96 1H, d, PhH); (6.70-6.71 1H, d, PhH); 5.04 (2H, s, NCH ₂Ph); 4.43-4.47 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.92 (3H, s, CH ₃); 2.73-2.77 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.12-2.16 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-9-butyl-7-(4-fluorine benzyloxy)-B-carboline (462): take 1-methyl-7-hydroxyl-9-butyl-B-carboline and 4-fluorine cylite as raw material, get white crystal, yield 76.5%, m.p.123-124 ℃; MS:m/e363; IR (KBr) ν: 3422.6,1650-3050,1621.7,1510.5,1448.2,1324.8,1225.5,1139.2,1037.2,813.1cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.28-8.29 (1H, d, H-5); (7.98-7.99 1H, d, H-3); (7.74-7.75 1H, d, H-4); (7.46-7.49 2H, m, H-8, H-6); (7.08-7.12 2H, t, PhH); (6.91-6.97 2H, m, PhH); 5.17 (2H, s, NCH ₂Ph); 4.41-4.45 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.02 (3H, s, CH ₃); 1.76-1.79 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 1.38-1.44 (2H, m, NCH ₂CH ₂CH ₂CH ₃); 0.95-0.98 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

Embodiment B-18:

7,9-two replaces the general synthesis technique of Yageine derivates (463-464):

Get 1-methyl-B-carboline-7-alcohol (10mmol) and place round-bottomed flask, add DMF; Wait dissolving rear adding 24mmol sodium hydride, then add corresponding halogenated alkane (24mmol).Until (about general response time 30min) after the raw material complete reaction, reactant liquor is poured in the 50ml water, use ethyl acetate (400ml, minute four extractions) to be extracted in the water and have (with the TLC monitoring, existing without product point onboard) without product.Organic facies with the washing of 200ml washing twice, 100ml saturated sodium-chloride once added anhydrous sodium sulfate drying 5 hours, the filtering desiccant is concentrated into extract dried, adds the 40ml dehydrated alcohol, it is an amount of to add concentrated hydrochloric acid, and solid is dissolved fully, transfers pH2-3, be concentrated into a small amount of liquid of residue, add a small amount of acetone, cold preservation is more than 10 hours, filter, solid washes twice with petroleum ether, and solid is poured in the 50ml water, add sodium bicarbonate and transfer pH about 8, divide four extractions, organic addition anhydrous sodium sulfate drying with the 200ml ethyl acetate, add activated carbon decolorizing, leave standstill about 5 hours, cross silica gel G, use the ethyl acetate rinse silica gel G, liquid under waiting to filter exists without product, stop flushing, filtrate is concentrated into dried, add the petroleum ether recrystallization, cold preservation was treated crystallization about 10 hours, filter, with the petroleum ether flushing, obtain chemical compound.

1-methyl-7-benzyloxy-9-benzyl-B-carboline (463): take 1-methyl-7-hydroxy-beta-carboline and cylite as raw material, get white crystal, yield 68.5%, m.p.154-156 ℃; IR (KBr) ν: 1650-3100,1620.9,1495.3,1446.7,1356.3,1228.7,1138.8,1032.2,820.4cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.31-8.32 (1H, d, H-5); (8.03-8.05 1H, d, H-3); (7.81-7.82 1H, d, H-4); (7.26-7.44 8H, m, H-8, H-6, PhH); (6.98-7.02 3H, m, PhH); (6.86-6.87 1H, d, PhH); 5.72 (2H, s, NCH ₂Ph); 5.11 (2H, s, NCH ₂Ph); 2.88 (3H, s, CH ₃).

7-(4-fluorine benzyloxy)-1-methyl-9-(4-luorobenzyl)-B-carboline (464): 1-methyl-7-hydroxy-beta-carboline and 4-fluorine cylite are raw material, get white crystal, yield 78.2%, m.p.183-185 ℃; IR (KBr) ν: 1650-3100,1621.6,1509.5,1446.1,1340.4,1225.5,1136.2,1038.1,816.2cm ^-1; ¹H-NMR (CDCl ₃, 400MHz) δ 8.32-8.33 (1H, d, H-5); (8.03-8.05 1H, d, H-3); (7.81-7.82 1H, d, H-4); (7.37-7.41 2H, m, H-8, H-6); (6.94-7.08 7H, m, PhH); (6.80-6.81 1H, d, PhH); 5.69 (2H, s, NCH ₂Ph); 5.07 (2H, s, NCH ₂Ph); 2.87 (3H, s, CH ₃).

Embodiment B-19:

2,7,9-three replaces the general synthesis technique of Yageine derivates (465-469):

7,9-two replaces yageine (10mmol), adds an amount of ethyl acetate it is dissolved fully, adds corresponding halogenated alkane (15-30mmol), and reflux 1-8 hour, be cooled to room temperature, filter the solid of separating out.Solid washs with a small amount of ethyl acetate, subsequently solid is dissolved in the dehydrated alcohol, and reflux is to clarification, and filtered while hot is placed the refrigerator recrystallization, gets crystal.

1-methyl-2-benzyl-7-(4-fluorine benzyloxy)-9-(4-luorobenzyl)-B-carboline bromine salt (465): take 1-methyl-7-(4-fluorine benzyloxy)-9-(4-luorobenzyl)-B-carboline and cylite as raw material, get pale yellow crystals, yield 72.6%, m.p.262-263 ℃; IR (KBr) ν: 1650-3050,1622.8,1510.1,1458.1,1350.4,1255.9,1156.6,1135.5,1032.1,829.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.82-8.84 (1H, d, H-5); (8.69-8.71 1H, d, H-3); (8.47-8.49 1H, d, H-4); (7.49-7.54 3H, m, H-8, H-6, PhH); (7.35-7.41 3H, m, PhH); (7.11-7.24 7H, m, PhH); (6.99-7.03 2H, m, PhH); 5.99 (4H, s, NCH ₂Ph); 5.26 (2H, s, NCH ₂Ph); 2.85 (3H, t, CH ₃).

1-methyl-2-benzyl-7-(3-chlorine benzyloxy)-9-phenylpropyl-B-carboline bromine salt (466): take 1-methyl-7-(3-chlorine benzyloxy)-9-phenylpropyl-B-carboline and cylite as raw material, get pale yellow crystals, yield 71.4%, m.p.206-208 ℃; IR (KBr) ν: 1650-3050,1623.1,1578.4,1514.4,1453.1,1344.9,1246.5,1154.1,1135.3,1032.6,815.9cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.76-8.78 (1H, d, H-5); (8.60-8.62 1H, d, H-3); (8.40-8.42 1H, d, H-4); (7.63 1H, s, H-8); (7.12-7.53 15H, m, H-6, PhH); 6.02 (2H, s, NCH ₂Ph); 5.35 (2H, s, NCH ₂Ph); 4.65-4.69 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.95 (3H, t, CH ₃); 2.64-2.68 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.03-2.06 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-2-benzyl-7-(4-fluorine benzyloxy)-9-phenylpropyl-B-carboline bromine salt (467): take 1-methyl-7-(4-fluorine benzyloxy)-9-phenylpropyl-B-carboline and cylite as raw material, get the milky crystal, yield 64.8%, m.p.216-218 ℃; MS:m/e 276; IR (KBr) ν: 1650-3050,1622.3,1580.0,1510.9,1455.1,1345.2,1253.9,1153.8,1138.4,1029.5,834.0cm ^-1 ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.76-8.78 (1H, d, H-5); (8.60-8.62 1H, d, H-3); (8.39-8.41 1H, d, H-4); (7.59-7.63 2H, m, H-8, H-6); (7.38-7.44 4H, m, PhH); (7.14-7.27 10H, m, PhH); 6.02 (2H, s, NCH ₂Ph); 5.30 (2H, s, NCH ₂Ph); 4.66-4.68 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.95 (3H, t, CH ₃); 2.65-2.69 (2H, t, NCH ₂CH ₂CH ₂Ph); 2.03-2.07 (2H, m, NCH ₂CH ₂CH ₂Ph).

1-methyl-9-butyl-2-benzyl-7-(4-fluorine benzyloxy)-B-carboline bromine salt (468): take 1-methyl-9-butyl-7-(4-fluorine benzyloxy)-B-carboline and cylite as raw material, get yellow crystals, yield 71.7%, m.p.220-222 ℃; IR (KBr) ν: 3418.3,1650-3000,1621.9,1578.5,1512.6,1455.4,1349.3,1245.0,1199.7,1135.5,822.8cm ^-1 ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.84-8.86 (1H, d, H-5); (8.27-8.28 1H, d, H-3); (8.13-8.16 1H, d, H-4); (7.46-7.50 2H, m, H-8, H-6); (7.31-7.34 3H, m, PhH); (7.19-7.21 2H, d, PhH); (7.09-7.14 3H, m, PhH); (6.95-6.96 1H, d, PhH); 6.34 (2H, s, NCH ₂Ph); 5.24 (2H, s, NCH ₂Ph); 4.45-4.49 (2H, t, NCH ₂CH ₂CH ₂CH ₃); 3.29 (3H, s, CH ₃); 1.74-1.82 (4H, m, NCH ₂CH ₂CH ₂CH ₃); 0.95-0.98 (3H, t, NCH ₂CH ₂CH ₂CH ₃).

1-methyl-7-benzyloxy-2,9-dibenzyl-B-carboline bromine salt (469): take 1-methyl-7-benzyloxy-9-benzyl-B-carboline and cylite as raw material, get yellow crystals, yield 78.4%, m.p.254-256 ℃; IR (KBr) ν: 1650-3050,1621.7,1516.3,1453.8,1350.0,1255.7,1158.4,1135.1,1029.7,822.2cm ^-1; ¹H-NMR (DMSO-d ₆, 400MHz) δ 8.82-8.84 (1H, d, H-5); (8.70-8.72 1H, d, H-3); (8.47-8.49 1H, d, H-4); (7.54-7.55 1H, d, H-8); (7.47-7.49 2H, m, H-6, PhH); (7.21-7.41 10H, m, PhH); (7.10-7.12 2H, d, PhH); (6.97-6.99 2H, d, PhH); 5.98-6.01 (4H, d, NCH ₂Ph); 5.27 (2H, s, NCH ₂Ph); 2.85 (3H, s, CH ₃).

Pharmacologically active

The antibacterial activity in vitro screening of Yageine derivates

1. experiment purpose

260 chemical compounds are carried out the Preliminary screening of antibacterial activity in vitro, for next step antibiotic expansion sieve experiment lays the first stone.

2. experiment material

2.1 experimental apparatus

Biohazard Safety Equipment BSC-1300IIA/B3 Shanghai Boxun Industrial Co., Ltd. instrument factory

Vertical self-controlled electric heating pressure steam sterilizer LDZX-40SC Shenan Medical Appliances Factory, Shanghai

Appearance sound refrigerator BCD-201YQA section dragon electrical equipment

Biochemical cultivation case SPX-250B-Z Shanghai Boxun Industrial Co., Ltd. instrument factory

Electric drying oven with forced convection 101 Beijing are bright Medical Instruments factory forever

Microwave oven MK-2270M Hai-er Microwave Products Co., Ltd., Qingdao

Electronic balance JM5102 Yuyao inscription calibration equipment company limited of weighing of recording

Magnetic force heating stirrer 79-1 Jiangsu Province Jintan City's Medical Instruments factory

Multiple spot inoculation instrument ORIENTAL MOTOR CO., LTD.

2.2 experimental strain

Experiment bacterial strain uses therefor 27 strains, 25 strain clinical isolates wherein, 2 strain Quality Control bacterium, the bacterial strain situation sees Table 1 in detail:

Table 1: external primary dcreening operation bacterial strain uses therefor details tabulation

2.3 testing sample

260 of testing samples with electronic balance precision weighing 0.0051g, dissolve with a small amount of DMSO, add an amount of purified water, and the sample solution 2ml that is mixed with final concentration and is 2560ug/ml is for subsequent use.The sample title sees Appendix 1. mutually

2.4 experiment reagent

MH culture medium lot number 20110718 Beijing extensive and profound in meaning star biotechnology Co., Ltd

2.5 positive control

2.5.1 Levofloxacin Hydrochloride Injection

Authentication code: the accurate word H19990324 of traditional Chinese medicines

Date of manufacture: on 04 08th, 2011

Batch number: 11040831

Manufacturer: Yangzijiang Pharmaceutical Group Co., Ltd

Effective dose: 2ml/0.1g

Get this medicine 102ul adding sterile distilled water 1.898ul and make the solution for standby that concentration is 2560ug/ml.

2.5.2 vancomycin hydrochloride for injection

Import drugs registration certificate number: H20080356

Date of manufacture: on December 11st, 2010

Batch number: WM20382

Manufacturer: Eli Lilly Japan K.K, Seishin Laboratories

Specification: 500mg/ bottle

Precision takes by weighing this medicine with electronic balance precision weighing 0.0051g, adds an amount of purified water, and the sample solution 2ml that is mixed with final concentration and is 2560ug/ml is for subsequent use.

3. experimental procedure

3.1 the preparation of pastille agar

According to 2 times of dilution methods, with 3 samples respectively diluted concentration be 2560ug/ml, 1280ug/ml, 640ug/ml, get respectively 1ml add a series ofly carried out labelling, internal diameter is in the flat board of 90mm.Get again after the thawing in 50 ℃ of water-baths the MH agar 19ml more than the balance 0.5h add dull and stereotyped in (Yao Wu ︰ agar=1 ︰ 19), the limit edged rocks flat board, makes the abundant mixing of medicine and culture medium.

3.2 bacterium liquid preparation

Each bacterium of the new purification of picking is diluted to 0.5Mcfarland respectively, 100 times of inoculations of redilution, and namely inoculum density is bacteria containing amount 10 ⁶Cfu/ml.

3.3 inoculation

Flat board is inoculated one by one on horizontal stand with 3GN90K multiple spot inoculation instrument, this inoculation instrument once can be inoculated 28 strain bacterium.Every quantity of microorganism inoculated is 1-2ul.Should inoculate first during inoculation and contain the low flat board of concentration, then inoculation contains the high flat board of concentration, and it is dull and stereotyped that at last inoculation does not contain the growth control of antibacterials, to check the existing state of test bacterium in the whole experimentation.

3.4 hatch

Can the mobile horizontal plate after vaccination bacterium liquid is done, put 37 ℃ and hatch 24-36h.

3.5 the result judges

The lowest concentration of drug that colony growth is suppressed fully is the MIC of this medicine to the detection bacterium.Single colony growth can be ignored.

4. experimental result

154 common bacterium MIC of HMD chemical compound In Vitro Anti are tabulating unit as a result: μ g/ml

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

106 common bacterium MIC of HMD chemical compound In Vitro Anti are tabulating unit as a result: μ g/ml

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Claims

1. the application in the preparation anti-infectives suc as formula the chemical compound shown in the I and pharmaceutically acceptable salt thereof

2. the application in the preparation anti-infectives suc as formula the chemical compound shown in the II and pharmaceutically acceptable salt thereof

3. the chemical compound shown in formula III and pharmaceutically acceptable salt thereof the application in the preparation anti-infectives

4. the application in the preparation anti-infectives suc as formula the chemical compound shown in the IV and pharmaceutically acceptable salt thereof

5. the application in the preparation anti-infectives suc as formula the chemical compound shown in the V and pharmaceutically acceptable salt thereof

6. the application in the preparation anti-infectives suc as formula the chemical compound shown in the VI and pharmaceutically acceptable salt thereof

R ⁷Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-6; R ⁹Be selected from hydrogen; replace or non-substituted C1-10 straight or branched alkyl; hydroxyl; replace or non-substituted C1-10 straight or branched alkoxyl; sulfydryl; replace or non-substituted C1-10 straight or branched alkylthio group; C1-10 alcoxyl C1-10 alkyl; aldehyde radical; replace or non-substituted C1-10 straight or branched alkanoyl; carboxyl; replace or non-substituted C1-10 straight or branched alkyl-ester group; replace or non-substituted C1-10 straight or branched alkanoyloxy; carbamoyl; the alkene of C2-10; halogen; nitro; cyano group; replace or five non-substituted or hexa-atomic aryl; replace or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl of O or S; replace or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl (CH) _h-and h be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH) of O or S _i-and i be selected from the integer of 1-6, replace or five non-substituted or hexa-atomic aryl-CO-(CH) _j-and j be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl-CO-(CH) of O or S _k-and i be selected from the integer of 1-6;

7. suc as formula the application of the chemical compound shown in the VII in the preparation anti-infectives

R2 is selected from, replacement or non-substituted C1-10 straight or branched alkyl, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6;

8. suc as formula the application of the chemical compound shown in the VIII in the preparation anti-infectives

R ²Be selected from, replacement or non-substituted C1-10 straight or branched alkyl, replacement or five non-substituted or hexa-atomic aryl (CH ₂) _f-and f be selected from the integer, replacement of 1-6 or non-substituted contain 1-4 and be selected from N, heteroatomic five or the six membered heteroaryl (CH of O or S ₂) _g-and g be selected from the integer of 1-6;

9. the application in the preparation anti-infectives suc as formula the chemical compound shown in the IX and pharmaceutically acceptable salt thereof

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

10. the application in the preparation anti-infectives suc as formula the chemical compound shown in the X and pharmaceutically acceptable salt thereof

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

11. the application in the preparation anti-infectives suc as formula the chemical compound shown in the XI and pharmaceutically acceptable salt thereof

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

12. the application in the preparation anti-infectives suc as formula the chemical compound shown in the XII and pharmaceutically acceptable salt thereof

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6;

13. the application in the preparation anti-infectives suc as formula the chemical compound shown in the XIII and pharmaceutically acceptable salt thereof

M is selected from the arbitrary integer of 0-6;

N is selected from the arbitrary integer of 0-6.

14. each application is characterized in that among the claim 1-3, described infection is to be caused by antibacterial.

15. application according to claim 14 is characterized in that, described antibacterial is selected from gram negative bacteria, Gram-positive bacterium.

16. application according to claim 14, it is characterized in that described antibacterial is selected from acinetobacter, Bacillus, campylobacter, chlamydia, the coating Pseudomonas, fusobacterium, the citric acid Pseudomonas, Escherichia, the intestinal Pseudomonas, Enterococcus, Francisella, haemophilus, Helicobacter, the white stone Bacillus of Cray, listeria, do not draw all and belong to, Mycobacterium, Neisser is Pseudomonas, proteus, Rhodopseudomonas, Salmonella, Serratia, Shigella, Stenotrophomonas belongs to, staphylococcus, chain shape Coccus or Nie Ersen Pseudomonas.

17. application according to claim 14, it is characterized in that described antibacterial is selected from staphylococcus aureus, staphylococcus epidermidis, enterococcus faecalis, enterococcus faecalis, escherichia coli, Klebsiella Pneumoniae, bacillus pyocyaneus, clostridium perfringen, motionless clostridium perfringen, moraxelle catarrhalis or escherichia coli.