CN107793388A

CN107793388A - Flat board mycin analog and its preparation method and application

Info

Publication number: CN107793388A
Application number: CN201710660705.XA
Authority: CN
Inventors: 段燕文; 沈奔; 黄勇; 朱湘成; 邱林; 田凯
Original assignee: CHANGSHA CIHANG MEDICAMENTS GRADUATE SCHOOL Co Ltd; HAYAO CIHANG PHARMACEUTICAL CO Ltd; CHANGSHA TIANCI BIO-PHARMACEUTICAL TECHNOLOGY Co Ltd
Current assignee: CHANGSHA CIHANG MEDICAMENTS GRADUATE SCHOOL Co Ltd; HAYAO CIHANG PHARMACEUTICAL CO Ltd; CHANGSHA TIANCI BIO-PHARMACEUTICAL TECHNOLOGY Co Ltd
Priority date: 2016-10-14
Filing date: 2017-08-04
Publication date: 2018-03-13
Anticipated expiration: 2037-08-04
Also published as: CN107793388B

Abstract

The present invention relates to a kind of flat board mycin analog and its preparation method and application, by the way that using flat board mycin as raw material, using acid as catalyst, using water and/or alcohol as solvent, flat board mycin acid-like substance of the present invention is obtained by heating response.Syntheti c route of the present invention is short, and safe operation is simple, readily available flat board mycin analog, there is provided diversity compound scaffold, can be widely applied to new medicament screen and pharmaceutical field.

Description

Flat board mycin analog and its preparation method and application

Technical field

The present invention relates to a kind of flat board mycin analog and its preparation method and application, belong to new drug synthesis technical field.

Background technology

Drug resistance pathogenic bacterial infection and diabetes are all the major diseases for seriously endangering human health.In recent years, with anti- Raw element is clinically widely used, is increasing, and the bacterial resistance because of unreasonable abuse appearance, adverse reaction, suprainfection The problems such as be also on the rise, anti-infective therapy is failed, cause the incidence of disease and case fatality rate to rise and medical expense increase, to clinic Treatment brings many difficulties, and great threat is caused to human health.Drug-resistant bacteria is more and more, and resistance scope is more and more wider, journey More and more higher is spent, bacterial drug resistance has turned into the Tough questions of anti-infective therapy of world field face.Therefore, bacterial resistance is controlled Property, it is abnormal urgent to find the antibiotic with novel mechanism, new construction.

Flat board mycin (platensimycin, PTM) peaceful laminin (platencin, PTN) is in recent years newfound one The class potent antibiotics sensitive to gram-positive bacteria.Their discovery is widely regarded as modern antibiotics research milestone formula One of achievement.Flat board mycin peace laminin structure is similar, and they are by a caged Fourth Ring or three ring beta-unsaturated ketones and a 3- Amino -2,4- dihydroxy-benzoic acids side chain is each formed by connecting by amido link, and (flat board mycin is shown in chemical structural formula (1) peace Laminin is shown in chemical structural formula (2)).The antibacterial mechanisms of flat board mycin peace laminin, which come from it, to be synthesized with bacterial fatty acid Enzyme high selectivity combines, so as to block the biosynthetic process of aliphatic acid.Aliphatic acid is one of complete key element of bacterial cell membrane, Thus the missing of aliphatic acid causes bacterial death.

In addition, flat board mycin may also be used for treating diabetes.After periodically taking flat board mycin to the mouse for suffering from diabetes, The level of the triglyceride in ill rat liver can not only be effectively reduced, and its sensitivity to insulin can be improved Property.This also can effectively block the In vitro cell experiment complete one of the biosynthesis pathway of mammal fat acid with flat board mycin Cause.

Therefore, flat board mycin peace laminin is class formation novelty, the drug leads of superior activity, has potential medicine With value.

Although flat board mycin external activity is stronger, activity in vivo has certain limitation.Using infect the mouse of S. aureus L-forms as Model, flat board mycin is persistently inputted to it can effectively treat S. aureus L-forms infection, and oral or hypodermic injection flat board mycin treatment is imitated Fruit is poor.Main cause be its internal clearance rate height, pharmacodynamics performance it is undesirable (Proc.Nat.Acad.Sci., 2011,108, 5378).And it is expected to obtain the excellent new drug of pharmacodynamic profiles by chemical modification and the screening of new congener.Therefore, from 2006 Since year, a variety of methods be used to developing flat board mycin analog (Tetrahedron Lett., 2008,49,3648； Chem.Commun.,2008, 5034；Tetrahedron Lett.,2009,50,5182；J.Antibiot.,2009,62, 699；J.Nat.Prod.,2011,74,329； Org.Lett.,2010,12,1744；Bio.Med.Chem.Lett.,2009, 19,1623；J.Am.Chem.Soc.,2008,130, 13110；J.Am.Chem.Soc.,2007,129,14850； Org.Biomol.Chem.,2014,12,486；Chem.Eur.J., 2011,17,3352；Chem.Eur.J.,2010,16, 9616.), to obtain the compound of more preferably pharmacokinetic property.But the flat board mycin analog of existing synthesis All there is no preferable bioactivity.

The content of the invention

For the above-mentioned deficiency of prior art, the present invention provides a kind of novel flat-plate mycin analog and its synthetic method, Structure such as formula (I), formula (II), formula (III), formula (IV), the formula (V) of novel flat-plate mycin analog are shown.

Wherein, in formula (I), R is the alkyl of hydrogen or 1-10 carbon atom；R is preferably the alkyl of 1-6 carbon atom；R is preferred For ethyl, n-propyl, normal-butyl；Ar¹One kind in following structure:

X is hydrogen, fluorine, chlorine, bromine or iodine；R¹For hydrogen or methyl；R²For hydroxyl, amido or methoxyl group；R³For hydrogen or methyl； R⁴ For hydrogen or methyl；

Ar²For:Aromatic group, 2- thienyls, methyl, ethyl or n-propyl；The aromatic group is preferably phenyl, 4- first Base phenyl, 4- trifluoromethyls, 4- fluorophenyls, 4- chlorphenyls, 3- trifluoromethyls, 2- trifluoromethyls, 3- fluorobenzene Base, 2- fluorophenyls, 1- naphthyls, 2- naphthyls, 9- anthryls.Flat board mycin acid and ester are that one kind has specific drugs intermediate compound The important skeleton structure of thing.The synthetic method (Bio.Med.Chem.Lett., 2009,19,1623) of existing report has multistep The shortcomings that operation, severe reaction conditions etc. are obvious.

The invention provides the synthetic method of a kind of acid of flat board mycin as shown in formula (eq.1) and ester, used in preparation method Catalyst it is cheap and easy to get, syntheti c route is short, simple to operate.

Wherein, catalyst is sulfuric acid, hydrogen chloride, trifluoromethanesulfonic acid, p-methyl benzenesulfonic acid, acetic acid, aluminium chloride, hexafluorophosphoric acid Copper；

R is hydrogen, methyl, ethyl, n-propyl, normal-butyl.

Present invention also offers a kind of synthetic method of novel flat-plate mycin analog as shown in formula (eq.2), with substitution Arylamine and flat board mycin acid are raw material, the method that a step builds novel flat-plate mycin analog.

Present invention also offers a kind of synthetic method of novel flat-plate mycin sulfur containing analogs as shown in formula (eq.3).It is flat Shown in the structural formula such as formula (III) of plate mycin analog, its preparation method comprises the following steps：With flat board mycin and thio phenyl first Acid and its derivative are raw material, and its reaction equation is：

Wherein, Ar²For：Phenyl, 4- aminomethyl phenyls, 4- trifluoromethyls, 4- fluorophenyls, 4- chlorphenyls, 4- bromophenyls, 3- trifluoromethyls, 2- trifluoromethyls, 3- fluorophenyls, 2- fluorophenyls, 3,5- difluorophenyls, 3,5- bis- trifluoromethyls Phenyl, 1- naphthyls, 2- naphthyls, 9- anthryls, 2- thienyls, methyl, ethyl and n-propyl etc..

Catalyst is：Triethylamine, diisopropyl ethyl amine (DIPEA), the carbon -7- alkene (DBU) of 1,8- diazabicylo 11, N-methylmorpholine, N, N- lutidines (DMAP), cesium carbonate, potassium carbonate, sodium carbonate etc..

Present invention also offers such as formula (eq.4) and the flat board mycin sulfur-containing compound as shown in formula (eq.5) and poly- second two The connection preparation method of alcohol, using flat board mycin sulfur-containing compound as raw material, its reaction equation is：

Preferably, in formula (eq.4), catalyst is triethylamine, diisopropyl ethyl amine (DIPEA), 1,8- diazabicylo 11 carbon -7- alkene (DBU), N-methylmorpholine, N, N- lutidines (DMAP) cesium carbonate, potassium carbonate and sodium carbonate etc..

Preferably, in formula (eq.5), catalyst any can produce univalent copper ion to be general in click chemistry Catalyst.Preferably, the catalyst of formula (eq.4 and eq.5) is copper sulphate, stannous chloride, cuprous bromide, cuprous iodide etc..

It is of the invention preferred, formula (eq.1) middle plateform mycin:Catalyst:The mol ratio of solvent is：1.0:(0.001-0.5): (100-1000), preferably ratio is：1.0：(0.01-0.1)：(100-500)

Preferably, formula (eq.1) described solvent is water, methanol, ethanol, normal propyl alcohol and n-butanol.

The step of preparation method one of the present invention, which prepares flat board mycin acid or ester, preparation method, to be included：Flat board is added in reaction bulb Mycin and solvent, are stirred at room temperature, add catalysts and solvents, are warming up to return stirring 12 hours at 80 DEG C, rotation Boil off except solvent obtains crude product, through column chromatography, obtain the flat board mycin acid or ester such as formula (I).

Flat board mycin and solvent are added in reaction bulb, is stirred at room temperature, adds catalysts and solvents, is heated up Stirred to 50-100 DEG C 4-24 hours, revolving removes solvent and obtains crude product, through column chromatography, obtains the described of formula (I) such as and puts down Plate mycin analog.

Preferably, arylamine in formula (eq.2):Flat board mycin acid:2- (7- azos BTA)-N, N, N', N'- tetramethyls Base urea hexafluorophosphoric acid ester (HATU):The mol ratio of triethylamine is：(1.0-5.0):1.0:(1.0-5.0):(3.0-6.0), preferably Ratio be：(1.0-2.0)： 1.0：(1.0-2.0):(3.0-4.0).

Preferably, the catalyst of formula (eq.2) is 2- (7- azos BTA)-N, N, N ', N '-tetramethylurea hexafluoro Phosphate (HATU), dicyclohexylcarbodiimide (DCC), 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides Or N, N'- DIC (DIC) (EDCI).

Preferably, formula (eq.2) described solvent is DMF, tetrahydrofuran, dichloromethane or three chloromethanes Alkane.

Preferably, formula (eq.2) preparation method includes：Arylamine, flat board mycin acid, 2- (7- azobenzenes are added in reaction bulb And triazole)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU), triethylamine and organic solvent, 12 is stirred at room temperature Hour, revolving removes solvent and obtains crude product, through column chromatography, obtains the flat board mycin analog such as formula (II).

Preferably, formula (eq.3) middle plateform mycin:Catalyst:The mol ratio of solvent is：1.0:(0.1-0.001).It is preferred that Ground, flat board mycin:Catalyst:The mol ratio of solvent is：1.0:0.2.

Preferably, formula (eq.3) described catalyst is triethylamine, diisopropyl ethyl amine (DIPEA), 1,8- diaza two Carbon -7- the alkene (DBU) of ring 11, N-methylmorpholine, N, N- lutidines (DMAP) or potassium carbonate.

Preferably, formula (eq.3) described solvent is dichloromethane, chloroform, 1,2- dichloroethanes, ethyl acetate, second Nitrile, ethanol or acetone etc..

Preferably, flat board mycin acid, thiobenzoate, catalyst and organic solvent are added in reaction bulb, at room temperature It is stirred, stirs 12 hours, revolving removes solvent and obtains crude product, and through column chromatography, the flat board obtained such as formula (III) is mould Plain analog.

Preferably, formula (eq.4) described solvent is dichloromethane, chloroform, 1,2- dichloroethanes, ethyl acetate, second Nitrile, ethanol or acetone etc..

Preferably, formula (eq.5) described solvent is water, dichloromethane, chloroform, 1,2- dichloroethanes, ethyl acetate, Acetonitrile, ethanol or acetone etc..

Catalyst in each reaction equation of the present invention represents catalyst.

Present invention also offers flat board mycin analog to suppress the application of drug-fast bacteria activity.Example shows, the portion of synthesis Divide novel flat-plate mycin analog to show the inhibitory activity to drug-fast bacteria (staphylococcus aureus), can be used as effectively anti-resistance to Medicine bacteria inhibitor is applied to field of medicaments.The present invention provides application of the flat board mycin in terms of antibacterials are prepared

The present invention has the advantage that and had the beneficial effect that：Synthesis is cheap and easy to get using catalyst, and syntheti c route is short, operation letter Single, cost is low, greatly improves raw material availability.The present invention can quickly and easily synthesizing new flat board mycin analog, be advantageous to It is further derivative, so as to provide multifarious flat board mycin analog, have to new medicament screen and pharmaceutical technology very important Meaning.

Embodiment

With reference to specific examples below, the present invention is described in further detail, protection content of the invention is not limited to Following examples.Under the spirit and scope without departing substantially from inventive concept, those skilled in the art it is conceivable that change and advantage All it is included in the present invention, and using appended claims as protection domain.Implement the process, condition, examination of the present invention Agent, experimental method etc., it is the universal knowledege and common knowledge of this area in addition to the following content specially referred to, the present invention Content is not particularly limited.

MOH represents that solvent is water, methanol, ethanol, normal propyl alcohol or n-butanol, and corresponding M is hydrogen, methyl, ethyl, n-propyl Or normal-butyl.

Embodiment 1：Flat board mycin (0.20mmol) is weighed, is placed it into reaction bulb, 7.0ml pure water is added, in room temperature After lower stirring 5 minutes, it is positioned in -10 DEG C.Weigh the concentrated sulfuric acid (0.10mmol) to be dissolved in pure water, be slowly added dropwise into reaction system In, it is warming up at 80 DEG C and stirs 12 hours, revolving removes solvent, obtains crude product；Pass through column chromatography (eluant, eluent again：Petroleum ether： Ethyl acetate=1：20~1：5) isolate to obtain flat board mycin acid PTMA-1, yield 90%.

Product PTMA-1 structural formulas are：

PTMA-1 is characterized as：¹H NMR(500MHz,CDCl₃) δ 6.46 (d, J=10.1Hz, 1H), 5.88 (d, J= 10.1Hz, 1H), 4.42 (s, 1H), 2.41 (t, J=6.5Hz, 1H), 2.38-2.31 (m, 2H), 2.31-2.21 (m, 2H), 2.13-2.05 (m, 1H), 2.05-1.96 (m, 2H), 1.87 (dd, J=11.2,3.5Hz, 1H), 1.81-1.68 (m, 2H), 1.60 (d, J=11.2Hz, 1H), 1.44 (s, 3H), 1.22 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ203.30,177.62,153.57,127.23,87.15,76.46,54.84, 46.31,45.94, 45.92,44.63,43.14,40.49,30.48,28.89,24.43,22.93；

HRMS(ESI)m/z calcd for C₁₇H₂₃O₄, [M+H]⁺291.1596；Found:291.1597.

Embodiment 2：Flat board mycin (0.20mmol) is weighed, is placed it into reaction bulb, 7.0ml methanol is added, in room temperature After lower stirring 5 minutes, it is positioned in -10 DEG C.Weigh the concentrated sulfuric acid (0.10mmol) to be dissolved in methanol, be slowly added dropwise into reaction system In, it is warming up at 80 DEG C and stirs 12 hours, revolving removes solvent, obtains crude product；Pass through column chromatography (eluant, eluent again：Petroleum ether： Ethyl acetate=1：20~1：5) isolate to obtain flat board mycin acid PTMA-2, yield 95%.

Product PTMA-2 structural formulas are：

PTMA-2 is characterized as：¹H NMR(500MHz,CDCl₃) δ 6.43 (d, J=10.1Hz, 1H), 5.83 (d, J= 10.1Hz, 1H), 4.34 (s, 1H), 3.60 (s, 3H), 2.36 (t, J=6.5Hz, 1H), 2.32-2.13 (m, 5H), 2.03 (d, J=5.3Hz, 1H), 2.00-1.91 (m, 3H), 1.81 (dd, J=11.1,3.4Hz, 1H), 1.70 (ddd, J=19.0, 12.8,8.2Hz, 3H), 1.57 (d, J=11.1Hz, 1H), 1.39 (s, 3H), 1.18 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ203.21,173.74,153.55,127.18,86.96,76.41,54.87, 51.60, 46.27,45.93,45.91,44.60,43.11,40.53,30.72,29.09,24.47,22.98；

HRMS(ESI)m/z calcd for C₁₈H₂₅O₄, [M+H]⁺305.1753；Found:305.1753.

Embodiment 3：Flat board mycin (0.20mmol) is weighed, is placed it into reaction bulb, 7.0ml ethanol is added, in room temperature After lower stirring 5 minutes, it is positioned in -10 DEG C.Weigh the concentrated sulfuric acid (0.10mmol) to be dissolved in ethanol, be slowly added dropwise into reaction system In, it is warming up at 80 DEG C and stirs 12 hours, revolving removes solvent, obtains crude product；Pass through column chromatography (eluant, eluent again：Petroleum ether： Ethyl acetate=1：20~1：5) isolate to obtain flat board mycin acid PTMA-3, yield 95%.

Product PTMA-3 structural formulas are：

PTMA-3 is characterized as：¹H NMR(400MHz,CDCl₃) δ 6.43 (d, J=10.1Hz, 1H), 5.84 (d, J= 10.1Hz, 1H), 4.35 (s, 1H), 4.10-4.05 (m, 2H), 2.37 (t, J=6.5Hz, 1H), 2.32 (s, 1H), 2.30- 2.11 (m, 3H), 2.03 (dd, J=6.3,5.3Hz, 1H), 1.99-1.94 (m, 2H), 1.81 (dd, J=11.1,3.6Hz, 1H), 1.77-1.64 (m, 2H), 1.61-1.54 (m, 1H), 1.40 (s, 3H), 1.19 (s, 3H), 1.19 (dd, J=6.3, 3.2Hz,3H)；

¹³C NMR(101MHz,CDCl₃)δ203.25,173.31,153.51,127.22,86.96,76.44,60.35, 54.90, 46.27,45.94,44.62,43.13,40.55,30.70,29.32,24.50,23.00,14.18；

HRMS(ESI)m/z calcd for C₁₉H₂₇O₄,[M+H]⁺319.1909；Found:319.1912.

Embodiment 4：Flat board mycin (0.20mmol) is weighed, is placed it into reaction bulb, 7.0ml n-butanols are added, in room After the lower stirring of temperature 5 minutes, it is positioned in -10 DEG C.Weigh the concentrated sulfuric acid (0.10mmol) to be dissolved in n-butanol, be slowly added dropwise into reaction In system, it is warming up at 80 DEG C and stirs 12 hours, revolving removes solvent, obtains crude product；Pass through column chromatography (eluant, eluent again：Stone Oily ether：Ethyl acetate=1：20~1：5) isolate to obtain flat board mycin acid PTMA-4, yield 94%.

Product PTMA-4 structural formulas are：

PTMA-4 is characterized as：¹H NMR(400MHz,CDCl₃) δ 6.44 (d, J=10.1Hz, 1H), 5.85 (d, J= 10.1Hz, 1H), 4.36 (s, 1H), 4.02 (td, J=6.6,3.0Hz, 3H), 2.38 (t, J=6.5Hz, 1H), 2.27 (ddd, J=13.0,11.8,8.9Hz, 4H), 2.22-2.12 (m, 1H), 2.08-1.94 (m, 5H), 1.82 (dd, J=11.1, 3.6Hz, 2H), 1.77-1.64 (m, 3H), 1.62-1.50 (m, 5H), 1.41 (s, 3H), 1.35 (dd, J=12.9,5.2Hz, 4H), 1.20 (s, 3H), 0.90 (dd, J=8.6,6.2Hz, 3H)；

¹³C NMR(101MHz,CDCl₃)δ203.25,173.40,153.49,127.24,86.96,76.46,64.29, 54.91,46.27, 45.95,44.63,43.14,40.56,30.71,30.63,29.28,24.50,23.01,19.12, 13.71；

HRMS(ESI)m/z calcd for C₂₁H₃₀NaO₄,[M+Na]⁺369.2041；Found:369.2042.

Wherein, Ar¹For：

Embodiment 5：Weigh arylamine 1a-1 (0.20mmmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 1a-2, yield 85%.

Arylamine 1a-1 and product 1a-2 structural formulas are：

1a-2 is characterized as：

¹H NMR(400MHz,CDCl₃) δ 8.51 (d, J=38.2Hz, 1H), 8.01-7.93 (m, 2H), 7.64 (d, J= 8.7 Hz, 2H), 6.52 (d, J=10.1Hz, 1H), 5.90 (d, J=10.1Hz, 1H), 4.44 (s, 1H), 3.89 (s, 3H), 2.37 (ddd, J=21.6,14.1,4.8Hz, 4H), 2.30-2.15 (m, 3H), 2.13-2.03 (m, 3H), 2.00 (d, J= 11.4Hz,2H), 1.95–1.71(m,4H),1.64(s,2H),1.45(s,3H),1.25(s,3H)；

¹³C NMR(101MHz,CDCl₃)δ203.57,171.49,170.52,153.77,138.66,132.84, 127.40, 127.25,122.89,120.28,87.16,76.47,54.88,46.46,46.04,44.67,43.15,40.62, 33.36,31.31,24.46, 23.07.

HRMS(ESI)m/z calcd for C₂₅H₂₉NNaO₅,[M+Na]⁺446.1943；Found:446.1942.

Embodiment 6：Weigh arylamine 1b-1 (0.20mmol), flat board mycin sour (0.10mmol), the 2- (nitrogen of 7- azos benzo three Azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- bis- NMF, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes molten Agent obtains crude product, through column chromatography, obtains flat board mycin analog 1b-2, yield 65%.

Arylamine 1b-1 and product 1b-2 structural formulas are：

1b-2 is characterized as：¹H NMR(400MHz,MeOD)δ8.00–7.95(m,2H),7.79–7.66(m,2H),6.67 (d, J=10.1Hz, 1H), 5.91 (d, J=10.1Hz, 1H), 4.50 (d, J=15.2Hz, 1H), 2.50-2.35 (m, 4H), 2.35-2.14 (m, 4H), 2.14-2.00 (m, 4H), 1.88 (dd, J=7.8,4.5Hz, 2H), 1.84-1.72 (m, 2H), 1.45(s,3H), 1.28(s,3H)；

¹³C NMR(101MHz,MeOD)δ205.71,174.24,169.57,156.11,144.55,131.85,127.99, 120.25,88.84,80.95,78.14,56.00,47.92,47.48,47.40,46.22,44.02,41.61,33.25, 32.50,25.45, 25.25,23.30；

HRMS(ESI)m/z calcd for C₂₄H₂₈NO₅,[M+H]⁺410.1967；Found:410.1765.

Embodiment 7：Weigh arylamine 1c-1 (0.20mmol), flat board mycin sour (0.10mmol), the 2- (nitrogen of 7- azos benzo three Azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- bis- NMF, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes molten Agent obtains crude product, through column chromatography, obtains flat board mycin analog 1c-2, yield 63%.

Arylamine 1c-1 and product 1c-2 structural formulas are：

1c-2 is characterized as：HRMS:calcd for C₂₅H₂₉NNaO₅,[M+Na]⁺446.1943；Found:446.1944.

Embodiment 8：Weigh arylamine 1d-1 (0.20mmol), flat board mycin sour (0.10mmol), the 2- (nitrogen of 7- azos benzo three Azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- bis- NMF, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes molten Agent obtains crude product, through column chromatography, obtains flat board mycin analog 2d-1, yield 52%.

Arylamine 1d-1 and product 2d-1 structural formulas are：

2d-1 is characterized as：HRMS:calcd for C₂₅H₂₈FNNaO₅,[M+Na]⁺464.1849；Found:464.1853.

Embodiment 9：Weigh arylamine 1e-1 (0.20mmol), flat board mycin sour (0.10mmol), the 2- (nitrogen of 7- azos benzo three Azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- bis- NMF, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes molten Agent obtains crude product, through column chromatography, obtains flat board mycin analog 2e-1, yield 27%.

Arylamine 1e-1 and product 2e-1 structural formulas are：

2e-1 is characterized as：HRMS:calcd for C₂₅H₂₈ClNNaO₅,[M+Na]⁺480.1553；Found:480.1552.

Embodiment 10：Weigh arylamine 1f-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2f-1, yield 23%.

Arylamine 1f-1 and product 2f-1 structural formulas are：

2f-1 is characterized as：¹H NMR(500MHz,CDCl₃) δ 10.94 (s, 1H), 8.64 (d, J=9.1Hz, 1H), 8.15 (d, J=2.4Hz, 1H), 7.70-7.58 (m, 1H), 6.50 (d, J=10.1Hz, 1H), 5.93 (d, J=10.1Hz, 1H), 4.48(s, 1H),3.96(s,3H),2.52–2.39(m,4H),2.39–2.28(m,3H),2.10–2.00(m,5H),1.90 (dd, J=11.2,3.2Hz, 3H), 1.64 (d, J=11.2Hz, 4H), 1.47 (s, 3H), 1.30 (s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ203.42,167.48,153.57,140.58,137.29,133.28, 127.26, 122.16,116.46,114.63,87.00,76.50,54.90,52.65,46.43,46.10,46.05,44.69, 43.17,40.58,37.11, 33.19,31.93,30.89,30.04,29.37,27.09,24.49,23.03；

HRMS:calcd for C₂₅H₂₈BrNNaO₅,[M+Na]⁺524.1048；Found:524.1051.

Embodiment 11：Weigh arylamine 1g-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2g-1, yield 51%.

Arylamine 1g-1 and product 2g-1 structural formulas are：

2g-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 11.09 (d, J=10.8Hz, 1H), 8.63 (d, J=8.5Hz, 1H), 8.05 (d, J=8.0Hz, 1H), 7.49 (t, J=7.9Hz, 1H), 7.03 (t, J=7.6Hz, 1H), 6.53 (d, J= 10.1Hz, 1H), 5.96 (d, J=10.1Hz, 1H), 4.57 (s, 1H), 2.47 (dd, J=20.1,13.8Hz, 3H), 2.41- 2.24 (m, 3H), 2.18-2.01 (m, 4H), 1.97 (dd, J=16.2,13.1Hz, 2H), 1.80 (dd, J=11.7,7.0Hz, 1H), 1.65 (d, J=11.3Hz, 2H), 1.48 (s, 3H), 1.28 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ203.72,171.48,170.92,153.95,141.75,134.76, 131.53, 127.31,122.29,120.26,87.46,54.67,52.56,46.57,46.02,45.70,44.75,43.11, 40.47,33.16,31.08, 29.70,29.32,27.22,24.58,22.92；

HRMS:calcd for C₂₄H₂₈NO₅,[M+H]⁺410.1967；Found:410.1967.

Embodiment 12：Weigh arylamine 1h-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2h-1, yield 61%.

Arylamine 1h-1 and product 2h-1 structural formulas are：

2h-1 is characterized as：HRMS:calcd for C₂₄H₂₇FNO₅,[M+H]⁺428.1873；Found:428.1872.

Embodiment 13：

Arylamine 1i-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos BTA)-N, N are weighed, N', N'- tetramethylurea hexafluorophosphoric acid ester (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- dimethyl methyls Acid amides, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes solvent and obtained Crude product, through column chromatography, obtain flat board mycin analog 2i-1, yield 45%.

Arylamine 1i-1 and product 2i-1 structural formulas are：

2i-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 8.56 (s, 1H), 8.34-8.24 (m, 2H), 8.19 (d, J= 8.4 Hz, 2H), 7.75-7.64 (m, 2H), 7.09-6.97 (m, 2H), 6.50 (d, J=10.1Hz, 1H), 5.92 (d, J= 10.1Hz, 1H), 4.46 (s, 1H), 2.42 (s, 2H), 2.37 (d, J=2.8Hz, 4H), 2.23 (s, 3H), 2.16-1.97 (m, 7H),1.97– 1.83(m,3H),1.83–1.71(m,2H),1.64(s,2H),1.45(s,4H),1.26(s,3H).

¹³C NMR(101MHz,CDCl₃)δ203.91,171.50,153.91,151.55,147.80,138.28, 127.19, 119.53,113.97,87.00,86.23,76.46,55.15,54.87,50.30,49.69,46.77,46.12, 46.06,44.82,44.67, 44.44,43.13,42.62,40.59,40.56,36.25,34.38,33.28,32.92, 31.29,24.30,23.50,23.02.

HRMS:calcd for C₂₄H₂₇ClNO₅,[M+H]⁺444.1578；Found:444.1581.

Embodiment 14：Weigh arylamine 1j-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2j-1, yield 40%.

Arylamine 1j-1 and product 2j-1 structural formulas are：

2j-1 is characterized as：¹³C NMR(126MHz,CDCl₃)δ203.42,171.48,170.07,153.60,139.21, 135.88,129.97,127.31,123.30,120.53,114.77,87.08,76.51,55.18,54.93,50.47, 49.25,46.47,46.13 46.05,44.86,44.72,44.52,43.21,42.71,40.69,40.62,36.24, 34.09,33.73,33.32,33.26,31.16, 29.79,27.23,24.48,23.07,22.69；

HRMS:calcd for C₂₄H₂₇BrNO₅,[M+H]⁺488.1072；Found:488.1080.

Embodiment 15：Weigh arylamine 1k-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2k-1, yield 38%.

Arylamine 1k-1 and product 2k-1 structural formulas are：

2k-1 is characterized as：¹³C NMR(101MHz,CDCl₃)δ204.17,171.64,169.16,154.05,143.07, 141.35, 139.81,127.41,121.98,116.32,100.09,87.92,83.16,76.84,54.63,46.67, 46.05,45.41,44.79, 43.13,40.42,32.90,30.44,29.70,24.62,22.87；

HRMS:calcd for C₂₄H₂₇INO₅,[M+H]⁺536.0934；Found:536.0941.

Embodiment 16：Weigh arylamine 1l-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2l-1, yield 28%.

Arylamine 1l-1 and product 2l-1 structural formulas are：

2l-1 is characterized as：¹H NMR (400MHz, Acetone) δ 11.39 (s, 1H), 8.56 (dd, J=12.5,2.7Hz, 1H), 8.17 (dd, J=8.9,6.7Hz, 1H), 6.99-6.82 (m, 1H), 6.61 (d, J=10.1Hz, 1H), 5.83 (d, J= 10.1Hz, 1H), 4.45 (s, 1H), 2.77 (s, 1H), 2.48 (ddd, J=14.1,11.9,5.0Hz, 1H), 2.43-2.36 (m, 2H), 2.36-2.20 (m, 2H), 2.07-2.04 (m, 3H), 1.91-1.81 (m, 2H), 1.78 (dd, J=10.9, 3.5Hz, 1H), 1.71 (d, J=10.9Hz, 1H), 1.38 (s, 3H), 1.25 (s, 3H)；

¹³C NMR(101MHz,Acetone)δ202.50,171.54,168.77,164.73,153.74,144.43, 144.29, 133.99,133.88,126.68,111.33,109.19,108.96,106.55,106.27,86.55,76.11, 54.57,46.19,46.09, 45.95,44.74,42.69,40.38,33.15,30.87,23.98,22.48；

HRMS:calcd for C₂₄H₂₇FNO₅,[M+H]⁺428.1873；Found:428.1872.

Embodiment 17：Weigh arylamine 1m-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2m-1, yield 43%.

Arylamine 1m-1 and product 2m-1 structural formulas are：

2m-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 10.99 (s, 1H), 8.56 (d, J=9.1Hz, 1H), 7.96 (d, J=2.6Hz, 1H), 7.39 (dd, J=9.1,2.6Hz, 1H), 6.56 (d, J=10.1Hz, 1H), 5.98 (d, J= 10.1Hz, 1H), 4.63 (s, 1H), 2.57 (s, 1H), 2.47 (dd, J=13.3,6.8Hz, 2H), 2.39-2.23 (m, 2H), 2.21-2.00 (m, 4H), 1.94 (ddd, J=29.9,15.1,10.8Hz, 1H), 1.82 (dd, J=11.7,6.8Hz, 1H), 1.67 (d, J=11.1Hz, 1H), 1.50 (s, 3H), 1.29 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ204.02,171.67,169.15,154.00,140.28,134.35, 130.95, 127.37,127.30,121.59,115.87,87.87,76.82,54.65,46.64,46.06,45.46, 44.78,43.12,40.43,32.90, 30.60,24.62,22.86；

HRMS(ESI)m/z calcd for C₂₄H₂₇FNO₅,[M+H]⁺428.1873；Found:428.1876.

Embodiment 18：Weigh arylamine 1n-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2n-1, yield 51%.

Arylamine 1n-1 and product 2n-1 structural formulas are：

2n-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 11.59 (s, 1H), 8.47 (d, J=8.4Hz, 1H), 7.40 (d, J=7.2Hz, 1H), 6.93-6.72 (m, 2H), 6.47 (d, J=10.0Hz, 1H), 6.36 (s, 1H), 5.89 (d, J= 10.0Hz, 1H), 4.44 (s, 1H), 2.42 (dd, J=22.9,8.8Hz, 3H), 2.35-2.25 (m, 2H), 2.22 (dd, J= 14.3,5.2Hz, 1H),2.01(s,2H),1.99(s,1H),1.93–1.80(m,2H),1.80–1.72(m,1H),1.60(d, J=11.1Hz, 2H), 1.43 (s, 3H), 1.26 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ203.41,171.63,167.80,153.59,142.12,133.68, 127.27, 117.38,110.07,109.84,87.03,76.48,54.86,46.44,46.00,45.98,44.66,43.15, 40.58,33.29,31.02, 24.53,23.03；

HRMS(ESI)m/z calcd for C₂₄H₂₇ClNO₅,[M+H]⁺444.1578；Found:444.1576.

Embodiment 19：Weigh arylamine 1o-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2o-1, yield 68%.

Arylamine 1o-1 and product 2o-1 structural formulas are：

2o-1 is characterized as：¹H NMR (400MHz, MeOD) δ 8.64 (dd, J=8.4,0.7Hz, 1H), 8.24 (d, J= 7.8Hz, 1H), 7.84 (dd, J=3.3,1.4Hz, 1H), 7.59-7.55 (m, 1H), 7.23-7.18 (m, 1H), 6.62 (d, J =10.1Hz, 1H), 5.87 (d, J=10.1Hz, 1H), 4.47 (s, 1H), 2.46-2.38 (m, 3H), 2.33 (dd, J= 12.2,5.7Hz, 1H), 2.30-2.19 (m, 2H), 2.11-2.01 (m, 4H), 1.89-1.76 (m, 3H), 1.70 (d, J= 11.2Hz,1H),1.42(s, 3H),1.21(s,3H).

¹³C NMR(101MHz,MeOD)δ204.25,172.49,167.23,154.72,139.18,138.11,132.36, 132.00,126.37,121.16,120.36,87.34,76.54,54.36,46.99,46.34,45.87,45.84,44.67, 42.45,40.08, 32.55,31.19,23.74,21.78；

HRMS(ESI)m/z calcd for C₂₄H₂₈N₂NaO₄,[M+Na]⁺431.1946；Found:431.1946.

Embodiment 20：Weigh arylamine 1p-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2p-1, yield 52%.

Arylamine 1p-1 and product 2p-1 structural formulas are：

2p-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 11.13 (s, 1H), 8.57 (dd, J=8.9,5.1Hz, 1H), 7.55 (t, J=4.9Hz, 1H), 7.42 (dd, J=6.2,2.6Hz, 1H), 6.79 (d, J=59.0Hz, 2H), 6.50 (dd, J =9.9,4.1 Hz, 1H), 5.92 (dd, J=10.0,4.6Hz, 1H), 4.46 (s, 1H), 2.41 (d, J=12.6Hz, 3H), 2.35-2.17 (m, 2H), 2.17-1.96 (m, 4H), 1.88 (s, 4H), 1.64 (d, J=10.9Hz, 2H), 1.47 (d, J= 4.1Hz,3H),1.26(s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ203.55,171.50,170.52,153.75,138.66,132.81, 127.41, 127.25,122.89,120.30,87.16,76.47,54.89,46.46,46.09,46.03,44.69,43.16, 40.61,33.38,31.36, 24.44,23.06；

HRMS(ESI)m/z calcd for C₂₄H₂₇FN₂NaO₄,[M+Na]⁺449.1852；Found:449.1851.

Embodiment 21：Weigh arylamine 1q-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2q-1, yield 46%.

Arylamine 1q-1 and product 2q-1 structural formulas are：

2q-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 10.96 (s, 1H), 8.55 (dd, J=9.1,5.2Hz, 1H), 7.27-7.22 (m, 1H), 7.23-7.13 (m, 1H), 6.81-6.53 (m, 2H), 6.49 (d, J=10.1Hz, 1H), 5.91 (d, J=10.1Hz, 1H), 4.46 (s, 1H), 2.48-2.31 (m, 5H), 2.25 (s, 2H), 2.15-1.95 (m, 5H), 1.85 (ddd, J=25.0,16.0,5.0Hz, 5H), 1.62 (d, J=11.0Hz, 2H), 1.45 (s, 3H), 1.25 (s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ203.56,171.41,170.51,153.73,136.23,127.27, 123.55, 119.89,119.72,114.00,113.81,87.15,76.51,54.92,46.50,46.13,46.05, 44.72,43.18,40.61,33.26, 31.38,24.45,23.05；

HRMS(ESI)m/z calcd for C₂₄H₂₇ClN₂NaO₄,[M+Na]⁺465.1556；Found:465.1556.

Embodiment 22：Weigh arylamine 1r-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2r-1, yield 18%.

Arylamine 1r-1 and product 2r-1 structural formulas are：

2r-1 is characterized as：¹H NMR(500MHz,CDCl₃) δ 10.95 (s, 1H), 8.49 (d, J=9.1Hz, 1H), 8.09 (d, J=2.4Hz, 1H), 7.50 (dd, J=9.0,2.4Hz, 1H), 6.54 (d, J=10.1Hz, 1H), 5.96 (d, J= 10.1Hz, 1H), 4.61 (s, 1H), 2.46 (t, J=6.1Hz, 1H), 2.40 (dd, J=11.4,4.7Hz, 1H), 2.30 (ddd, J=20.2,11.7,4.3 Hz, 3H), 2.16-2.09 (m, 1H), 2.06-1.97 (m, 3H), 1.97-1.87 (m, 1H), 1.80 (dd, J=11.4,6.3Hz, 1H), 1.66 (s, 1H), 1.47 (s, 3H), 1.26 (s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ203.96,171.65,169.00,153.90,140.82,137.28, 133.91, 127.43,121.85,116.17,114.59,87.88,76.85,54.67,46.66,46.08,45.50, 44.83,43.15,40.43,32.82, 30.49,24.63,22.88；

HRMS(ESI)m/z calcd for C24H28BrN2O4,[M+H]⁺487.1232；Found:487.1237.

Embodiment 23：Weigh arylamine 1s-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2s-1, yield 16%.

Arylamine 1s-1 and product 2s-1 structural formulas are：

2s-1 is characterized as：¹H NMR(400MHz,CDCl₃) δ 11.52 (s, 1H), 8.45 (dd, J=11.8,2.6Hz, 1H), 7.58 (dd, J=8.8,6.0Hz, 1H), 6.84-6.69 (m, 1H), 6.61 (d, J=27.9Hz, 2H), 6.50 (d, J= 10.1Hz, 1H), 5.91 (d, J=10.1Hz, 1H), 4.47 (s, 1H), 2.50-2.36 (m, 4H), 2.30 (ddd, J=17.3, 14.7,8.9Hz, 3H), 2.07 (s, 3H), 2.03 (dd, J=7.7,3.5Hz, 3H), 1.94-1.83 (m, 2H), 1.83-1.73 (m,2H),1.65(s,2H), 1.46(s,3H),1.26(s,3H)；

¹³C NMR(101MHz,CDCl₃)δ203.42,171.49,170.89,153.65,142.50,129.45, 127.23, 114.27,109.84,108.33,107.95,87.11,76.48,54.87,46.44,46.07,46.03, 44.68,43.15,40.59,33.40, 31.20,24.45,23.06；

HRMS(ESI)m/z calcd for C₂₄H₂₇FN₂NaO4,[M+Na]⁺449.1852；Found:449.1853.

Embodiment 24：Weigh arylamine 1t-1 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2t-1, yield 42%.

Arylamine 1t-1 and product 2t-1 structural formulas are：

2t-1 is characterized as：¹H NMR (400MHz, MeOD) δ 8.01 (d, J=8.3Hz, 1H), 7.46 (td, J=8.4, 6.4Hz, 1H), 6.98 (dd, J=10.5,8.5Hz, 1H), 6.67 (d, J=10.1Hz, 1H), 5.90 (d, J=10.1Hz, 1H),4.49(s, 1H),2.49–2.34(m,4H),2.34–2.25(m,2H),2.25–2.17(m,1H),2.15–2.01(m, 4H), 1.93-1.78 (m, 4H), 1.75 (d, J=11.2Hz, 1H), 1.44 (s, 3H), 1.27 (s, 3H)；

¹³C NMR(101MHz,MeOD)δ204.38,172.51,167.19,161.31,158.85,154.88,138.80, 132.00,131.91,126.40,118.22,111.14,110.90,87.42,76.60,54.39,47.04,46.44, 45.89,44.67, 42.48,40.11,32.42,31.02,23.71,21.81；

HRMS(ESI)m/z calcd for C₂₄H₂₇FN₂NaO4,[M+Na]⁺449.1852；Found:449.1854.

Embodiment 25：Weigh arylamine 1a-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2a-2, yield 87%.

Arylamine 1a-2 and product 2a-2 structural formulas are：

2a-2 is characterized as：¹H NMR(500MHz,CDCl₃) δ 8.33 (s, 1H), 8.04 (s, 1H), 7.91 (d, J=7.9Hz, 1H), 7.72 (d, J=7.7Hz, 1H), 7.35 (t, J=7.9Hz, 1H), 6.48 (d, J=10.1Hz, 1H), 5.88 (d, J= 10.1Hz, 1H), 4.44 (s, 1H), 3.87 (s, 3H), 2.41 (t, J=6.5Hz, 1H), 2.37-2.14 (m, 5H), 2.03 (ddd, J=25.9,20.4,8.3Hz, 4H), 1.89 (ddd, J=13.3,10.9,5.6Hz, 1H), 1.84-1.71 (m, 2H), 1.60 (d, J=11.2Hz, 1H), 1.42 (s, 3H), 1.23 (s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ204.49,171.40,166.84,154.31,138.63,130.72, 129.04, 127.08,124.90,124.18,120.47,87.12,76.46,54.90,52.17,46.95,46.14, 46.11,44.68,43.06,40.56, 32.84,31.40,24.29,22.99；

HRMS(ESI)m/z calcd for C₂₅H₂₉NNaO₅,[M+Na]⁺446.1943；Found:446.1943.

Embodiment 26：Weigh arylamine 1b-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2b-2, yield 42%.

Arylamine 1b-2 and product 2b-2 structural formulas are：

2b-2 is characterized as：¹H NMR(400MHz,CDCl₃) δ 8.96 (d, J=6.8Hz, 1H), 7.87 (s, 1H), 7.82- 7.71 (m, 1H), 7.20-7.07 (m, 1H), 6.51 (d, J=10.1Hz, 1H), 5.92 (d, J=10.1Hz, 1H), 4.44 (s, 1H), 3.89 (s, 3H), 2.43 (t, J=6.5Hz, 2H), 2.35 (d, J=7.0Hz, 1H), 2.33-2.24 (m, 2H), 2.09 (d, J=9.6 Hz, 2H), 2.03 (dd, J=16.4,7.7Hz, 3H), 1.86 (dd, J=11.4,3.1Hz, 2H), 1.76 (s, 2H), 1.71 (s, 3H), 1.63 (d, J=11.1Hz, 2H), 1.45 (s, 3H), 1.26 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ204.24,170.97,165.78,154.02,127.15,126.80, 126.13, 123.31,115.03,114.83,87.17,76.47,54.88,52.26,46.96,46.16,46.13,44.66, 43.11,40.58,33.02, 31.38,24.23,23.01；

HRMS(ESI)m/z calcd for C₂₅H₂₈FNNaO₅,[M+Na]⁺464.1849；Found:464.1846.

Embodiment 27：Weigh arylamine 1c-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2c-2, yield 34%.

Arylamine 1c-2 and product 2c-2 structural formulas are：

2c-2 is characterized as：¹H NMR(400MHz,CDCl₃) δ 8.99 (s, 1H), 7.94 (s, 1H), 7.74 (dd, J=8.4, 2.0 Hz, 1H), 7.46 (d, J=8.4Hz, 1H), 6.53 (d, J=10.1Hz, 1H), 5.95 (d, J=10.1Hz, 1H), 4.47 (s, 1H), 3.92 (s, 3H), 2.45 (t, J=6.4Hz, 2H), 2.35 (ddd, J=12.8,11.9,6.7Hz, 4H), 2.19- 2.01 (m, 5H), 1.91 (ddd, J=14.5,8.7,3.1Hz, 3H), 1.86-1.76 (m, 2H), 1.65 (d, J=11.2Hz, 3H),1.47(s,3H), 1.29(s,4H)；

¹³C NMR(101MHz,CDCl₃)δ204.07,171.20,166.21,154.00,134.82,129.95, 129.70, 129.09,127.15,125.59,122.74,87.06,76.49,54.88,52.34,46.83,46.18, 46.12,44.67,43.12,40.58, 33.07,30.30,24.25,23.01；

HRMS(ESI)m/z calcd for C₂₅H₂₈ClNNaO₅,[M+Na]⁺480.1553；Found:480.1554.

Embodiment 28：Weigh arylamine 1d-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2d-2, yield 43%.

Arylamine 1d-2 and product 2d-2 structural formulas are：

2d-2 is characterized as：¹H NMR(400MHz,CDCl₃) δ 8.23 (d, J=20.0Hz, 1H), 7.96 (dd, J=6.1, 2.7 Hz, 1H), 7.93-7.83 (m, 1H), 7.10 (t, J=9.6Hz, 1H), 6.54 (d, J=10.1Hz, 1H), 5.93 (d, J =10.0 Hz, 1H), 4.46 (s, 1H), 3.93 (s, 3H), 2.45 (t, J=6.5Hz, 1H), 2.35 (d, J=7.6Hz, 2H), 2.30 (dd, J=13.9,2.9Hz, 1H), 2.22 (dd, J=17.1,5.9Hz, 1H), 2.18-2.08 (m, 2H), 2.04 (dd, J=17.3,7.3Hz, 2H), 1.98-1.86 (m, 3H), 1.82 (dd, J=13.4,6.6Hz, 2H), 1.65 (d, J= 11.2Hz,1H),1.47(s,3H), 1.27(s,3H)；

¹³C NMR(101MHz,CDCl₃)δ204.65,171.37,164.60,154.45,134.40,134.37, 127.14, 126.03,122.69,118.58,118.47,117.48,117.25,87.14,76.46,54.88,52.41, 47.07,46.13,46.10, 44.67,43.07,40.57,32.89,31.53,24.28,22.99；

HRMS(ESI)m/z calcd for C₂₅H₂₈FNNaO₅,[M+Na]⁺464.1849；Found:464.1848.

Embodiment 29：Weigh arylamine 1e-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2e-2, yield 34%.

Arylamine 1e-2 and product 2e-2 structural formulas are：

2e-2 is characterized as：¹H NMR(400MHz,CDCl₃) δ 8.51 (s, 1H), 8.02 (s, 1H), 7.59 (d, J=6.9Hz, 1H), 7.16 (t, J=8.0Hz, 1H), 6.50 (d, J=10.1Hz, 1H), 5.92 (d, J=10.0Hz, 1H), 4.43 (s, 1H), 3.92 (s, 3H), 2.41 (dd, J=12.0,5.2Hz, 2H), 2.38-2.32 (m, 2H), 2.32-2.19 (m, 2H), 2.13-1.95 (m, 4H), 1.95-1.73 (m, 5H), 1.62 (d, J=11.2Hz, 2H), 1.44 (s, 3H), 1.25 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ204.27,171.65,164.77,154.24,127.78,127.16, 125.94, 125.82,124.02,123.98,118.33,87.17,76.48,54.87,52.41,46.97,46.12, 44.66,43.11,40.57,33.08, 31.40,24.24,23.00.

HRMS(ESI)m/z calcd for C₂₅H₂₈FNNaO₅,[M+Na]⁺464.1849；Found:464.1850.

Embodiment 30：Weigh arylamine 1f-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2f-2, yield 73%.

Arylamine 1f-2 and product 2f-2 structural formulas are：

2f-2 is characterized as：¹H NMR(500MHz,CDCl₃) δ 8.96 (s, 1H), 8.53 (d, J=8.2Hz, 1H), 7.98 (s, 1H), 7.79 (d, J=7.7Hz, 1H), 7.41 (t, J=7.9Hz, 2H), 6.55 (d, J=10.1Hz, 1H), 5.96 (d, J= 10.0Hz, 1H), 4.68 (s, 1H), 2.52-2.42 (m, 3H), 2.27 (dd, J=18.5,5.9Hz, 1H), 2.20-2.12 (m, 1H), 2.12-1.97 (m, 3H), 1.94 (dd, J=11.4,3.1Hz, 1H), 1.86-1.73 (m, 2H), 1.69 (d, J= 11.4Hz,1H),1.51(s, 3H),1.28(s,3H).

¹³C NMR(126MHz,CDCl₃)δ204.29,171.78,169.00,154.15,139.27,130.25, 129.25, 127.32,125.06,124.93,120.55,87.93,76.48,54.82,46.49,46.12,46.00, 44.83,42.96,40.33,32.66, 32.21,29.69,24.44,22.75；

HRMS(ESI)m/z calcd for C₂₄H₂₈NO₅,[M+H]⁺410.1967；Found:410.1969.

Embodiment 31：Weigh arylamine 1g-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2g-2, yield 78%.

Arylamine 1g-2 and product 2g-2 structural formulas are：

2g-2 is characterized as：¹H NMR (400MHz, MeOD) δ 8.60 (d, J=6.3Hz, 1H), 7.84 (dd, J=6.7, 5.1Hz, 1H), 7.24 (dd, J=10.3,8.6Hz, 1H), 6.67 (d, J=10.1Hz, 1H), 5.91 (d, J=10.1Hz, 1H), 4.51 (s, 1H), 2.53-2.38 (m, 4H), 2.36-2.25 (m, 2H), 2.18-2.03 (m, 4H), 1.87 (ddd, J= 13.2,6.4,3.9Hz, 3H), 1.79 (dd, J=21.6,7.3Hz, 2H), 1.45 (d, J=2.3Hz, 3H), 1.28 (s, 3H)；

¹³C NMR(126MHz,MeOD)δ204.32,172.98,154.67,127.14,126.47,126.15,115.00, 114.84,87.35,76.63,54.45,46.45,45.94,45.90,44.70,42.52,40.09,31.21,31.03, 23.72,21.79；

HRMS(ESI)m/z calcd for C₂₄H₂₇FNO₅,[M+H]⁺428.1873；Found:428.1872.

Embodiment 32：Weigh arylamine 1h-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2h-2, yield 46%.

Arylamine 1h-2 and product 2h-2 structural formulas are：

2h-2 is characterized as：¹H NMR (400MHz, MeOD) δ 8.43 (s, 1H), 7.82 (d, J=8.3Hz, 1H), 7.54 (d, J=8.3Hz, 1H), 6.68 (d, J=10.2Hz, 1H), 5.92 (d, J=10.1Hz, 1H), 4.52 (s, 1H), 2.46 (t, J= 5.6Hz, 3H), 2.41-2.26 (m, 3H), 2.10 (dd, J=11.7,5.9Hz, 5H), 1.88 (ddd, J=13.1,9.7, 5.0Hz, 3H), 1.83-1.73 (m, 3H), 1.45 (d, J=4.0Hz, 4H), 1.29 (s, 3H)；

¹³C NMR(101MHz,MeOD)δ204.32,173.01,154.69,134.48,129.12,127.06,126.47, 87.38, 76.64,54.45,46.48,45.93,45.91,44.70,42.51,40.10,31.09,23.71,21.80；

HRMS(ESI)m/z calcd for C₂₄H₂₇ClNO₅,[M+H]⁺444.1578；Found:444.1575.

Embodiment 33：Weigh arylamine 1i-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2i-2, yield 80%.

Arylamine 1i-2 and product 2i-2 structural formulas are：

2i-2 is characterized as：¹H NMR (400MHz, MeOD) δ 8.08 (dd, J=6.4,2.6Hz, 1H), 7.86 (d, J= 4.4Hz, 1H), 7.72 (dd, J=4.9,2.7Hz, 1H), 7.21 (d, J=9.3Hz, 1H), 7.17-7.08 (m, 1H), 6.67 (d, J=10.1 Hz, 1H), 5.91 (d, J=10.1Hz, 1H), 4.51 (s, 1H), 2.49-2.34 (m, 4H), 2.26 (ddd, J =14.3,11.8,6.9 Hz, 3H), 2.17-2.00 (m, 5H), 1.88 (dd, J=11.1,6.9Hz, 3H), 1.77 (dd, J= 16.0,6.9Hz, 2H), 1.44 (d, J=4.2Hz, 3H), 1.27 (s, 3H)；

¹³C NMR(101MHz,MeOD)δ204.26,172.56,154.67,134.51,129.45,127.04,126.48, 123.58,123.05,116.48,116.25,87.34,76.61,54.48,46.44,45.95,45.89,44.71,42.52, 40.10,31.58, 31.15,23.74,21.80；

HRMS(ESI)m/z calcd for C₂₄H₂₇FNO₅,[M+H]⁺428.1873；Found:428.1873.

Embodiment 34：Weigh arylamine 1j-2 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2j-2, yield 77%.

Arylamine 1j-2 and product 2j-2 structural formulas are：

2j-2 is characterized as：¹H NMR (400MHz, MeOD) δ 8.06 (t, J=6.8Hz, 1H), 7.65 (dd, J=10.5, 3.8Hz, 1H), 7.20 (t, J=7.9Hz, 1H), 6.66 (d, J=10.1Hz, 1H), 5.92 (s, 1H), 4.51 (s, 1H), 2.54-2.39 (m, 4H), 2.39-2.24 (m, 3H), 2.17-1.99 (m, 5H), 1.88 (dd, J=8.9,3.9Hz, 3H), 1.77 (dd, J=20.9,7.2 Hz, 2H), 1.44 (s, 3H), 1.27 (s, 3H)；

¹³C NMR(126MHz,MeOD)δ204.35,173.05,154.71,127.88,127.03,126.48,124.30, 123.16,117.44,87.35,76.63,54.45,48.48,48.15,47.98,47.81,47.64,47.46,47.29, 47.12,46.49, 45.93,45.89,44.70,42.52,40.10,31.26,31.05,23.74,21.81；

HRMS(ESI)m/z calcd for C₂₄H₂₇FNO₅,[M+H]⁺428.1873；Found:428.1875.

Embodiment 35：Weigh arylamine 1a-3 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2a-3, yield 65%.

Arylamine 1a-3 and product 2a-3 structural formulas are：

2a-3 is characterized as：¹H NMR (400MHz, CDCl₃) δ 10.65 (s, 1H), 10.11 (s, 1H), 8.22 (s, 1H), 7.65 (s 1H), 6.53 (d, J=10.4Hz, 1H), 6.51 (s, 1H), 5.91 (d, J=10.1Hz, 1H), 4.45 (s, 1H), 3.87 (s, 3H), 2.44 (d, J=6.4Hz, 2H), 2.39-2.34 (m, 2H), 2.34-2.20 (m, 3H), 2.17-2.06 (m, 2H), 2.02 (dd, J=17.0,7.3Hz, 3H), 1.86 (dd, J=11.3,3.7Hz, 3H), 1.83-1.74 (m, 2H), 1.64 (d, J=11.3Hz, 2H), 1.45 (s, 3H), 1.26 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ204.65,173.32,169.89,161.02,155.96,154.55, 127.06, 123.49,119.18,106.04,104.55,87.36,76.48,54.84,52.07,47.04,46.14, 46.04,44.66,43.06,40.54, 32.01,31.62,24.25,22.96.

Embodiment 36：Weigh arylamine 1b-3 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2b-3, yield 73%.

Arylamine 1b-3 and product 2b-3 structural formulas are：

2b-3 is characterized as：¹H NMR(400MHz,CDCl₃) δ 8.18 (d, J=1.6Hz, 1H), 8.09 (s, 1H), 7.71 (s, 1H), 7.36 (d, J=1.7Hz, 1H), 6.49 (s, 1H), 5.91 (d, J=10.1Hz, 1H), 4.44 (s, 1H), 3.92 (s, 3H), 3.87 (s, 3H), 2.47-2.39 (m, 2H), 2.35 (d, J=5.8Hz, 2H), 2.33-2.25 (m, 2H), 2.13-2.05 (m, 2H), 2.05-1.97 (m, 3H), 1.88 (ddd, J=14.3,8.4,3.1Hz, 3H), 1.80 (s, 4H), 1.62 (d, J= 11.2Hz,2H),1.44(s, 3H),1.26(s,3H)；

¹³C NMR(101MHz,CDCl₃)δ204.36,172.28,166.92,154.24,147.54,140.48, 127.19, 125.74,121.69,116.07,108.35,87.15,76.52,56.43,54.94,52.15,46.93, 46.19,44.74,43.17,40.63, 32.65,31.61,24.35,23.08.

Embodiment 37：Weigh arylamine 1c-3 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2c-3, yield 82%.

Arylamine 1c-3 and product 2c-3 structural formulas are：

2c-3 is characterized as：¹H NMR(400MHz,CDCl₃) δ 10.67 (s, 1H), 8.42 (d, J=2.9Hz, 1H), 8.07 (s, 2H), 7.01 (d, J=2.9Hz, 1H), 6.49 (d, J=10.1Hz, 1H), 5.92 (d, J=10.1Hz, 1H), 4.60 (s, 1H), 3.92 (s, 3H), 2.42 (dd, J=14.2,7.4Hz, 2H), 2.39-2.29 (m, 3H), 2.29-2.19 (m, 1H), 2.10-2.00 (m, 4H), 1.89 (dd, J=11.0,3.5Hz, 2H), 1.78 (dd, J=11.8,6.7Hz, 2H), 1.62 (d, J =11.2Hz, 2H), 1.46 (s, 3H), 1.27 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ204.09,172.09,170.42,153.89,148.85,143.81, 127.10, 113.66,111.54,108.75,87.03,76.54,54.85,52.43,46.80,46.08,44.72,43.15, 40.61,31.93,31.30, 24.27,22.98.

Embodiment 38：Weigh arylamine 1d-3 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2d-3, yield 56%.

Arylamine 1d-3 and product 2d-3 structural formulas are：

2d-3 is characterized as：¹H NMR(400MHz,CDCl₃) δ 10.30 (s, 1H), 9.03 (s, 1H), 8.35 (d, J= 9.1Hz, 1H), 7.68 (s, 1H), 7.26 (s, 1H), 6.48 (d, J=9.2Hz, 2H), 5.91 (d, J=10.1Hz, 1H), 4.45(s,1H), 4.09(s,4H),2.45–2.38(m,2H),2.38–2.29(m,3H),2.29–2.16(m,2H),2.15– 1.95 (m, 5H), 1.94-1.81 (m, 3H), 1.76 (dd, J=11.6,6.6Hz, 2H), 1.61 (d, J=11.1Hz, 2H), 1.44(s,3H),1.25(s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ204.07,170.88,169.94,155.68,153.89,149.60, 128.46, 127.20,119.54,107.51,99.43,86.98,76.50,54.90,53.10,46.80,46.12,46.08, 44.67,43.12,40.57, 32.89,31.56,24.33,23.03.

Embodiment 39：Weigh arylamine 1e-3 (0.20mmol), flat board mycin sour (0.10mmol), 2- (7- azos benzos three Nitrogen azoles)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid esters (HATU) (0.30mmol) are added in reaction bulb, add 1.0ml N, N- Dimethylformamide, it is stirred at room temperature；Triethylamine (0.45mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 2e-3, yield 78%.

Arylamine 1e-3 and product 2e-3 structural formulas are：

2e-3 is characterized as：

¹H NMR(400MHz,CDCl₃) δ 11.45 (s, 2H), 8.25 (s, 1H), 7.37 (d, J=10.8Hz, 1H), 6.53 (d, J=10.1Hz, 1H), 5.95 (d, J=10.1Hz, 1H), 4.46 (s, 1H), 3.94 (s, 3H), 2.57 (ddd, J= 14.8,12.0,5.5 Hz, 1H), 2.39 (ddt, J=15.9,11.8,5.4Hz, 5H), 2.08 (ddd, J=20.8,15.8, 8.4Hz, 4H), 1.99-1.75 (m, 4H), 1.65 (d, J=11.2Hz, 2H), 1.47 (s, 3H), 1.29 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ203.77,174.09,170.11,154.03,149.76,147.85, 145.49, 144.67,144.51,127.10,115.87,111.75,111.54,102.04,101.97,87.14,76.42, 54.86,52.48,46.73, 46.17,46.11,44.64,43.11,40.58,32.06,31.56,24.20,22.98.

Wherein, Ar²For：Phenyl, 4- aminomethyl phenyls, 4- trifluoromethyls, 4- fluorophenyls, 4- chlorphenyls, 4- bromophenyls, 3- trifluoromethyls, 2- trifluoromethyls, 3- fluorophenyls, 2- fluorophenyls, 3,5- difluorophenyls, 3,5- bis- trifluoromethylbenzenes Base, 1- naphthyls, 2- naphthyls, 9- anthryls, 2- thienyls, methyl, ethyl and n-propyl etc..

Embodiment 40：Weigh in thiobenzoate 3a (0.20mmol), flat board mycin (0.10mmol) addition reaction bulb, add Enter 2.0ml dichloromethane, be stirred at room temperature；DBU (0.02mmol) is slowly added to, continues stirring 12 hours, revolving removes Solvent obtains crude product, through column chromatography, obtains flat board mycin analog 4a, yield 89%.

Thiobenzoate 3a and product 4a structural formulas are：

4a is characterized as：1H NMR(400MHz,CDCl₃)δ11.77(s,1H),11.11(s,1H),8.22(s,1H), 7.90-7.81 (m, 2H), 7.50 (t, J=7.4Hz, 2H), 7.37 (t, J=7.8Hz, 2H), 6.45 (d, J=8.9Hz, 1H), 4.60 (s, 1H), 4.09 (t, J=3.7Hz, 1H), 3.22 (dd, J=14.7,4.4Hz, 1H), 2.73-2.67 (m, 1H), 2.66 (d, J=3.1Hz, 1H), 2.62 (d, J=3.1Hz, 1H), 2.51 (t, J=6.2Hz, 1H), 2.40 (s, 1H), 2.29 (dd, J=10.1,3.9Hz, 1H), 2.24 (s, 1H), 2.17 (d, J=11.6Hz, 1H), 2.11 (d, J=5.8Hz, 1H), 2.05 (dd, J=11.9,2.9Hz, 1H), 1.93 (ddd, J=14.2,10.4,6.3Hz, 1H), 1.83 (dd, J=11.4, 7.0Hz, 1H), 1.62 (d, J=11.8Hz, 1H), 1.43 (s, 3H), 1.32 (s, 3H)

¹³C NMR(101MHz,CDCl₃)δ213.04,190.09,174.07,172.94,155.38,154.54, 136.65, 134.13,128.95,128.51,127.61,114.53,111.41,103.96,87.31,77.20,53.39, 50.02,49.57,48.34, 46.17,45.65,43.72,42.80,40.66,33.18,32.57,26.45,22.95；

HRMS(ESI)m/zcalcd for C₃₁H₃₄NO₈S,[M+H]⁺580.2005；Found:580.1990.

Embodiment 41：Weigh thiobenzoate 3a (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Revolving removes solvent and slightly produced Product, through column chromatography, obtain flat board mycin analog 4a, yield 98%.

Thiobenzoate 3a and product 4a structural formulas are：

Embodiment 42：Weigh to chlorine thiobenzoate 3b (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Revolving removes solvent and slightly produced Product, through column chromatography, obtain flat board mycin analog 4b, yield 98%.

It is to chlorine thiobenzoate 3b and product 4b structural formulas：

4b is characterized as：¹H NMR(400MHz,CDCl₃) δ 11.89 (s, 1H), 8.25 (s, 1H), 7.82 (d, J=8.6Hz, 2H), 7.52 (d, J=8.9Hz, 1H), 7.36 (t, J=10.0Hz, 2H), 6.47 (d, J=8.9Hz, 1H), 4.61 (s, 1H), 4.09 (t, J=3.7 Hz, 1H), 3.24 (dd, J=14.8,4.3Hz, 1H), 2.71 (d, J=6.2Hz, 1H), 2.69 (d, J= 3.6Hz, 1H), 2.65 (d, J=3.1Hz, 1H), 2.53 (t, J=6.1Hz, 1H), 2.38 (s, 1H), 2.30 (d, J= 4.0Hz, 1H), 2.27 (d, J=3.1Hz, 1H), 2.19 (d, J=11.6Hz, 1H), 2.13 (d, J=14.1Hz, 1H), 2.05-2.01 (m, 1H), 2.01-1.92 (m, 1H), 1.85 (dd, J=11.1,7.0Hz, 1H), 1.63 (d, J=11.7Hz, 1H),1.45(s,3H),1.35(s,3H)；

¹³C NMR(101MHz,CDCl₃)δ212.97,188.65,173.70,172.68,155.05,154.19, 140.25, 134.70,128.96,128.66,128.24,114.23,111.06,103.87,86.91,77.27,53.18, 49.79,49.64,48.00, 46.00,45.34,43.48,42.43,40.43,32.91,32.36,26.18,22.71；

HRMS(ESI)m/zcalcd for C₃₁H₃₃ClNO₈S,[M+H]⁺614.1615；Found:614.1594.

Embodiment 43：Weigh to methoxyl group thiobenzoate 3c (0.20mmol), flat board mycin (0.10mmol) and carbonic acid Caesium (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Revolving removes solvent and obtained slightly Product, through column chromatography, obtain flat board mycin analog 4c, yield 95%.

It is to methoxyl group thiobenzoate 3c and product 4c structural formulas：

4c is characterized as：HRMS(ESI)m/zcalcd for C₃₂H₃₆NO₉S,[M+H]⁺610.2111；Found: 610.2095.

Embodiment 44：Weigh to methylthiobenzoic acid 3d (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving is gone Except solvent obtains crude product, through column chromatography, flat board mycin analog 4d, yield 72% are obtained.

It is to methylthiobenzoic acid 3d and product 4d structural formulas：

4d is characterized as：

¹H NMR(500MHz,CDCl₃) δ 11.89 (s, 1H), 11.14 (s, 1H), 8.27 (s, 1H), 7.80 (d, J= 8.1Hz, 2H), 7.73 (dd, J=5.7,3.3Hz, 1H), 7.56 (t, J=6.2Hz, 2H), 7.19 (d, J=8.0Hz, 2H), 6.49 (d, J=8.8Hz, 1H), 4.59 (s, 1H), 4.11 (t, J=3.7Hz, 1H), 3.24 (dd, J=14.7,4.4Hz, 1H), 2.69 (dd, J=10.2,3.5Hz, 2H), 2.65 (d, J=3.1Hz, 1H), 2.53 (t, J=6.3Hz, 1H), 2.43 (s, 2H), 2.40 (s, 1H), 2.37 (s, 3H), 2.30 (d, J=3.5Hz, 1H), 2.28 (d, J=2.8Hz, 1H), 2.19 (d, J= 11.6Hz, 1H), 2.14 (d, J=5.3 Hz, 1H), 2.05 (s, 2H), 1.97 (dd, J=14.8,9.4Hz, 2H), 1.86 (dd, J=11.2,7.0Hz, 1H), 1.79-1.69 (m, 2H), 1.65 (d, J=11.7Hz, 1H), 1.45 (s, 3H), 1.35 (s, 3H).

¹³C NMR(126MHz,CDCl₃)δ212.78,189.37,173.79,155.11,154.29,144.88, 133.92, 129.36,129.34,127.42,114.27,111.11,103.85,86.77,77.29,53.18,49.78, 49.21,48.12,46.02, 45.38,43.53,42.56,40.46,33.05,32.43,27.22,26.18,22.76, 21.68；

HRMS(ESI)m/zcalcd for C₃₂H₃₆NO₈S,[M+H]⁺594.2161；Found:594.2142.

Embodiment 45：Weigh to fluorine thiobenzoate 3e (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4e, yield 95%.

It is to fluorine thiobenzoate 3e and product 4e structural formulas：

4e is characterized as：

¹H NMR(500MHz,CDCl₃)δ11.85(s,1H),11.17(s,1H),8.25(s,1H),8.05–7.81(m, 2H), 7.55 (d, J=8.5Hz, 1H), 7.08 (t, J=8.0Hz, 2H), 6.49 (d, J=8.6Hz, 1H), 4.63 (s, 1H), 4.11 (s, 1H), 3.25 (dd, J=14.5,3.3Hz, 1H), 2.69 (s, 2H), 2.66 (s, 1H), 2.55 (s, 1H), 2.40 (s, 1H), 2.30 (d, J=9.5 Hz, 2H), 2.21 (d, J=11.6Hz, 1H), 2.16 (s, 1H), 2.06 (d, J=11.1Hz, 1H), 1.99 (d, J=16.2Hz, 2H), 1.87 (d, J=8.3Hz, 1H), 1.65 (d, J=11.5Hz, 1H), 1.47 (s, 3H),1.36(s,3H)；

¹³C NMR(126MHz,CDCl₃)δ212.64,188.30,173.74,172.76,164.87,155.09, 154.24, 132.79,130.03,129.94,128.24,114.29,111.14,103.88,86.71,77.25,53.23, 49.83,49.64,48.07, 46.13,45.35,43.52,42.49,40.47,33.04,32.52,26.11,22.76；

HRMS(ESI)m/zcalcd for C₃₁H₃₃FNO₈S,[M+H]⁺598.1911；Found:598.1898.

Embodiment 46：Weigh a fluorine thiobenzoate 3f (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4f, yield 92%.

Between fluorine thiobenzoate 3f and product 4f structural formulas be：

4f is characterized as：

¹H NMR(500MHz,CDCl₃) δ 11.97 (s, 1H), 11.20 (s, 1H), 8.21 (s, 1H), 7.67 (d, J= 7.6Hz, 1H), 7.58 (d, J=8.8Hz, 1H), 7.52 (d, J=8.8Hz, 1H), 7.33 (d, J=6.0Hz, 1H), 7.23 (d, J=7.7Hz, 1H), 6.45 (d, J=8.8Hz, 1H), 4.64 (s, 1H), 4.12 (s, 1H), 3.34-3.18 (m, 1H), 2.83-2.73 (m, 1H), 2.70 (d, J=7.4Hz, 1H), 2.67 (s, 1H), 2.61-2.48 (m, 2H), 2.30 (d, J= 12.0Hz, 2H), 2.21 (d, J=11.6Hz, 1H), 2.13 (d, J=12.0Hz, 2H), 1.96 (s, 2H), 1.86 (s, 1H), 1.63 (d, J=11.7Hz, 1H), 1.46 (s, 3H), 1.36 (s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ212.40,188.67,173.65,172.71,163.53,161.55, 154.94, 154.24,138.30,138.25,130.40,130.34,128.06,123.05,120.90,120.73, 114.26,114.08,111.06, 103.66,87.15,77.31,52.92,49.83,49.73,48.06,45.45,45.41, 43.40,42.41,40.30,32.46,32.03, 26.36,22.68；

HRMS(ESI)m/zcalcd for C₃₁H₃₃FNO₈S,[M+H]⁺598.1911；Found:598.1897.

Embodiment 47：Weigh adjacent fluorine thiobenzoate 3g (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4g, yield 92%.

Adjacent fluorine thiobenzoate 3g and product 4g structural formulas are：

4g is characterized as：

¹H NMR(400MHz,CDCl₃) δ 11.92 (s, 1H), 11.08 (s, 1H), 8.24 (d, J=19.7Hz, 1H), 7.92 (d, J=5.3Hz, 1H), 7.79 (s, 1H), 7.66-7.42 (m, 2H), 7.26-7.13 (m, 1H), 7.12-6.96 (m, 1H), 6.45 (d, J=7.9Hz, 1H), 4.58 (s, 1H), 4.10 (s, 1H), 3.23 (d, J=14.4Hz, 1H), 2.69 (s, 1H), 2.66 (s, 2H), 2.52 (s, 1H), 2.38 (d, J=9.4Hz, 1H), 2.27 (d, J=10.7Hz, 2H), 2.18 (d, J= 11.5Hz, 1H), 2.11 (d, J=12.4Hz, 1H), 2.08-1.99 (m, 2H), 1.94 (d, J=6.0Hz, 1H), 1.84 (s, 1H), 1.65 (d, J=9.9Hz, 2H), 1.45 (s, 3H), 1.33 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ212.61,188.32,186.68,173.78,172.86,161.49, 158.92, 154.93,154.30,134.93,129.92,129.70,128.25,114.19,110.96,104.12,86.93, 86.82,77.30,53.02, 49.73,49.41,47.95,45.86,45.29,43.47,42.27,40.42,32.86, 32.20,26.23,22.74；

HRMS(ESI)m/zcalcd for C₃₁H₃₃FNO₈S,[M+H]⁺598.1911；Found:598.1893.

Embodiment 48：Weigh to bromine thiobenzoate 3h (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4h, yield 85%.

It is to bromine thiobenzoate 3h and product 4h structural formulas：

4h is characterized as：¹H NMR(400MHz,CDCl₃)δ11.82(s,1H),11.20(s,1H),8.26(s,1H),7.73 (d, J=8.6 Hz, 2H), 7.50 (dd, J=8.7,4.8Hz, 3H), 6.46 (d, J=8.9Hz, 1H), 4.63 (s, 1H), 4.09 (t, J=3.4Hz, 1H), 3.24 (dd, J=14.8,4.2Hz, 1H), 2.77-2.68 (m, 2H), 2.66 (d, J=3.0Hz, 1H), 2.53 (d, J=6.1 Hz, 1H), 2.40 (s, 1H), 2.30 (d, J=2.8Hz, 1H), 2.27 (d, J=3.2Hz, 1H), 2.19 (d, J=11.7Hz, 1H), 2.15 (s, 1H), 2.05 (d, J=6.5Hz, 2H), 2.02-1.90 (m, 1H), 1.85 (dd, J=10.9,7.1Hz, 1H), 1.63 (d, J=11.7Hz, 1H), 1.46 (s, 3H), 1.35 (s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ213.11,188.85,173.71,172.53,155.08,154.17, 135.10, 131.93,128.98,128.71,128.19,114.25,111.08,103.66,87.01,77.31,53.15, 49.78,49.63,47.97, 45.93,45.33,43.45,42.39,40.42,32.86,32.31,26.23,22.69；

HRMS(ESI)m/zcalcd for C₃₁H₃₃BrNO₈S,[M+H]⁺658.1110；Found:658.1100.

Embodiment 49：Weigh to trifluoromethyl thiobenzoate 3i (0.20mmol), flat board mycin (0.10mmol) and carbon Sour caesium (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, rotation Boil off except solvent obtains crude product, through column chromatography, obtain flat board mycin analog 4i, yield 93%.

It is to trifluoromethyl thiobenzoate 3i and product 4i structural formulas：

4i is characterized as：

¹H NMR(400MHz,CDCl₃)δ11.89(s,1H),11.15(s,1H),8.29–8.17(m,1H),8.00(d,J =6.6Hz, 2H), 7.83 (d, J=7.6Hz, 1H), 7.67 (d, J=6.7Hz, 2H), 7.56 (s, 1H), 6.48 (s, 1H), 4.61 (s, 1H), 4.14 (s, 1H), 3.26 (d, J=12.6Hz, 1H), 2.67 (s, 2H), 2.54 (s, 1H), 2.38 (s, 1H), 2.29 (s, 2H), 2.18 (s, 2H), 2.05 (d, J=13.0Hz, 2H), 1.86 (s, 1H), 1.65 (d, J=11.0Hz, 1H), 1.46(s,3H),1.36(s, 3H)；

¹³C NMR(101MHz,CDCl₃)δ212.65,189.03,173.64,155.10,154.17,139.18, 135.11, 128.49,127.72,126.21,125.76,114.22,111.08,86.78,77.25,53.21,49.92, 49.79,47.99,46.12, 45.32,43.51,42.34,40.44,32.98,32.40,26.06,22.72；

HRMS(ESI)m/zcalcd for C₃₂H₃₃F₃NO₈S,[M+H]⁺648.1879；Found:648.1864.

Embodiment 50：Weigh m-trifluoromethyl thiobenzoate 3j (0.20mmol), flat board mycin (0.10mmol) and carbon Sour caesium (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, rotation Boil off except solvent obtains crude product, through column chromatography, obtain flat board mycin analog 4j, yield 70%.

M-trifluoromethyl thiobenzoate 3j and product 4j structural formulas are：

4j is characterized as：¹H NMR(400MHz,CDCl₃)δ11.89(s,1H),11.15(s,1H),8.29–8.17(m,1H), 8.00 (d, J=6.6Hz, 2H), 7.83 (d, J=7.6Hz, 1H), 7.67 (d, J=6.7Hz, 2H), 7.56 (s, 1H), 6.48 (s, 1H), 4.61 (s, 1H), 4.14 (s, 1H), 3.26 (d, J=12.6Hz, 1H), 2.67 (s, 2H), 2.54 (s, 1H), 2.38 (s, 1H), 2.29 (s, 2H), 2.18 (s, 2H), 2.05 (d, J=13.0Hz, 2H), 1.86 (s, 1H), 1.65 (d, J= 11.0Hz,1H),1.46(s,3H),1.36(s, 3H)；

Embodiment 51：Weigh o-trifluoromethyl thiobenzoate 3k (0.20mmol), flat board mycin (0.10mmol) and carbon Sour caesium (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, rotation Boil off except solvent obtains crude product, through column chromatography, obtain flat board mycin analog 4k, yield 20%.

O-trifluoromethyl thiobenzoate 3k and product 4k structural formulas are：

4k is characterized as：¹³C NMR(126MHz,CDCl₃)δ212.01,190.93,173.71,173.03,155.26, 154.33,132.01, 131.68,128.73,128.37,127.11,124.30,114.34,111.33,103.86,87.08, 77.34,52.98,50.53,49.89, 48.22,45.87,45.46,43.47,42.34,40.46,32.93,32.31, 27.32,22.77；

HRMS(ESI)m/zcalcd for C₃₂H₃₃F₃NO₈S,[M+H]⁺648.1879；Found:648.1857.

Embodiment 52：Weigh p nitrothiobenzoic acid 3l (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4l, yield 67%.

P nitrothiobenzoic acid 3l and product 4l structural formulas are：

4l is characterized as：¹³C NMR(101MHz,CDCl₃)δ213.31,188.40,173.64,172.38,155.04, 153.98,150.49, 140.82,128.29,128.12,123.79,114.17,111.11,103.60,86.96,77.28, 53.20,50.28,49.90,47.88, 45.99,45.31,43.45,42.22,40.44,32.63,32.32,26.32, 22.68；

HRMS(ESI)m/zcalcd for C₃₁H₃₃N₂O₁₀S,[M+H]⁺625.1856；Found:625.1840.

Embodiment 53：Weigh 3,5- difluoro thiobenzoate 3m (0.20mmol), flat board mycin (0.10mmol) and carbonic acid Caesium (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4m, yield 94%.

3,5- difluoro thiobenzoate 3m and product 4m structural formulas are：

4m is characterized as：¹³C NMR(126MHz,CDCl₃)δ212.02,187.59,173.57,172.81,163.73, 161.83,161.73, 154.78,154.24,139.11,127.92,114.25,110.98,110.88,110.47, 110.26,109.20,109.00,108.80, 105.16,103.62,87.19,77.27,52.75,50.18,49.89, 48.02,45.42,45.11,43.33,42.26,40.21,32.11, 31.86,26.41,22.66；

HRMS(ESI)m/zcalcd for C₃₁H₃₂F₂NO₈S,[M+H]⁺616.1816；Found:616.1807.

Embodiment 54：Weigh the trifluoromethyl thiobenzoate 3n (0.20mmol) of 3,5- bis-, flat board mycin (0.10mmol) Added with cesium carbonate (0.05mmol) in reaction bulb, add 2.0ml dichloromethane, be stirred at room temperature；It is small to continue stirring 12 When, revolving removes solvent and obtains crude product, through column chromatography, obtains flat board mycin analog 4n, yield 86%.

The trifluoromethyl thiobenzoate 3n of 3,5- bis- and product 4n structural formulas are：

4n is characterized as：¹H NMR(500MHz,CDCl₃)δ12.05(s,1H),11.22(s,1H),8.13(s,1H),7.48 (d, J=8.9 Hz, 1H), 7.37 (dd, J=18.2,5.4Hz, 2H), 6.95 (dd, J=17.4,7.9Hz, 2H), 6.41 (d, J =8.9Hz, 1H), 4.62 (s, 1H), 4.08 (t, J=3.4Hz, 1H), 3.32-3.17 (m, 1H), 3.10 (s, 1H), 2.97 (s, 1H), 2.76 (s, 2H), 2.65 (dd, J=14.8,2.7Hz, 1H), 2.56 (d, J=24.3Hz, 2H), 2.32-2.24 (m, 1H), 2.24-2.15 (m, 2H), 2.13 (d, J=9.3Hz, 2H), 2.00-1.88 (m, 1H), 1.83 (dd, J=10.8, 7.1Hz, 1H), 1.58 (d, J=11.7Hz, 1H), 1.43 (s, 3H), 1.33 (s, 3H)；

¹³C NMR(126MHz,CDCl₃)δ212.02,187.64,173.50,172.85,154.82,154.22, 138.09, 132.55,132.28,127.99,127.31,123.85,121.67,114.17,111.08,103.52,87.43, 77.27,52.89,50.91, 50.06,47.95,45.49,45.30,43.58,42.21,40.27,32.00,31.82, 26.33,22.70；

HRMS(ESI)m/zcalcd for C₃₃H₃₂F₆NO₈S,[M+H]⁺716.1753；Found:716.1731.

Embodiment 55：Weigh the thio thiophenic acid 3o (0.20mmol) of 2-, flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4o, yield 90%.

The thio thiophenic acid 3o of 2- and product 4o structural formulas are：

4o is characterized as：¹H NMR(500MHz,CDCl₃)δ11.85(s,1H),11.10(s,1H),8.26(s,1H),7.74 (d, J=3.7 Hz, 1H), 7.58 (d, J=4.9Hz, 1H), 7.54 (d, J=8.9Hz, 1H), 7.04 (d, J=4.0Hz, 1H), 6.47 (d, J=8.9 Hz, 1H), 4.60 (s, 1H), 4.10 (s, 1H), 3.23 (dd, J=14.7,4.2Hz, 1H), 2.69 (d, J =5.2Hz, 2H), 2.67-2.62 (m, 1H), 2.52 (s, 1H), 2.39 (s, 1H), 2.26 (d, J=9.1Hz, 2H), 2.16 (s, 1H), 2.13 (s, 1H), 2.06 (d, J=11.9Hz, 1H), 2.01-1.89 (m, 1H), 1.84 (dd, J=10.6, 7.1Hz, 1H), 1.64 (d, J=11.8Hz, 1H), 1.45 (s, 3H), 1.33 (s, 3H)；

HRMS(ESI)m/zcalcd for C₂₉H₃₂NO₈S₂,[M+H]⁺586.1569；Found:586.1555.

Embodiment 56：Weigh the thio naphthoic acid 3p (0.20mmol) of 2-, flat board mycin (0.10mmol) and cesium carbonate (0.05 Mmol) add in reaction bulb, add 2.0ml dichloromethane, be stirred at room temperature；Continue stirring 12 hours, revolving removes molten Agent obtains crude product, through column chromatography, obtains flat board mycin analog 4p, yield 90%.

The thio naphthoic acid 3p of 2- and product 4p structural formulas are：

4p is characterized as：¹³C NMR(126MHz,CDCl₃)δ213.01,189.71,173.65,172.90,154.16, 135.81,133.62, 132.19,129.55,128.93,128.77,128.56,127.76,127.00,122.79, 114.12,110.85,86.97,77.27,53.11, 49.79,49.56,48.10,45.85,45.38,43.50,42.53, 40.43,32.75,32.23,26.30,22.77；

HRMS(ESI)m/zcalcd for C₃₅H₃₆NO₈S,[M+H]⁺630.2161；Found:630.2145.

Embodiment 57：Weigh thioacetic acid 3q (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4q, yield 95%.

Thioacetic acid 3q and product 4q structural formulas are：

4q is characterized as：¹³C NMR(126MHz,CDCl₃)δ211.29,192.81,172.66,171.68,154.09, 153.25,127.19, 113.26,110.18,102.70,86.10,76.26,51.95,48.66,48.27,46.83, 44.57,44.32,42.28,41.38,39.29, 31.62,30.99,30.11,25.25,21.63；

HRMS(ESI)m/zcalcd for C₂₆H₃₂NO₈S,[M+H]⁺518.1848；Found:518.1834.

Embodiment 58：Weigh p-fluorophenyl thioacetic acid 3r (0.20mmol), flat board mycin (0.10mmol) and cesium carbonate (0.05 mmol) is added in reaction bulb, is added 2.0ml dichloromethane, is stirred at room temperature；Continue stirring 12 hours, revolving Remove solvent and obtain crude product, through column chromatography, obtain flat board mycin analog 4r, yield 93%.

P-fluorophenyl thioacetic acid 3r and product 4r structural formulas are：

4r is characterized as：¹³C NMR(126MHz,CDCl₃)δ212.16,195.66,173.68,172.85,163.38, 161.42, 155.20,154.34,131.35,131.28,128.77,128.27,115.80,115.62,114.38, 111.34,103.75,87.31, 77.34,52.85,49.89,49.70,49.61,47.92,45.37,43.40,42.28, 40.37,32.54,31.80,29.79,26.51, 22.73；

HRMS(ESI)m/zcalcd for C₃₂H₃₅FNO₈S,[M+H]⁺612.2067；Found:612.2048.

Embodiment 59：Inhibitory activity of the flat board mycin analog of the present invention to drug-fast bacteria (staphylococcus aureus).

Inhibition zone method test compound bacteriostatic activity：

Strain name:S.aureus 29213, MRSA115, MRSA116, MRSA117, MRSA118, MRSA119.

Experimentation:

1. with the strain of each test tube slant of oese picking in the sterilized water with bead, being vibrated several minutes with hand makes spore Son is scattered, and mixing spore suspension is made after filtering.

2. certain density mixing spore suspension 0.5mL is injected into each culture dish with aseptic straw (or syringe).To Injection 15ml-20ml fusing shape agar LB culture mediums (about 45 DEG C), bacterium solution is well mixed with culture medium, treated in each culture dish It is cooled down.

Carried disease germs 3. being homogeneously disposed in disk filter paper with tweezers on culture medium flat plate, by the 5 certain density compound solutions of μ l It is added drop-wise on filter paper, closes the lid and put under preference temperature, cultivate 12h, observes around filter paper disk the presence or absence of inhibition zone and big It is small.

Positive reference compound is flat board mycin, is born with reference to being blank solvent, Bactericidal test result see the table below 1.

Table 1：

Embodiment 60：Inhibitory activity of the flat board mycin analog of the present invention to drug-fast bacteria (staphylococcus aureus).

MIC test compound bacteriostatic activities：

Strain name:S.aureus 29213, MSSA2952, MSSA2952, MSSA2954, MSSA2955, MSSA2956, MRSA115, MRSA2968, MRSA3090, MRSA3071, MRSA3093, MRSA3110, MRSA3161.

Experimentation:

Strains tested is grown in LB culture mediums, and OD is diluted to LB culture mediums₆₂₅=0.005, after then drawing dilution Culture medium is to 96 orifice plates per the μ l of hole liquid 100.The test compound of various concentrations is added in different holes, positive reference compound For flat board mycin, it is blank solvent to bear reference.In the DMSO final concentrations of each well 1%, but the life of any test strain is not influenceed It is long.After cultivating 12h at a temperature of 37 DEG C, using the OD in each hole₆₂₅Value measure MIC value.

MIC determination experiment results see the table below 2：

Table 2：Antibacterial activities of 4in comparison to PTM,PTN and linezolid as measured by MICs (μg mL^-1)

Above test result indicates that：Contrasted with reference compound flat board mycin, some flat board mycin analogs in the present invention Certain bacteriostatic activity is showed, effective sterilization inhibitor can be used as to be applied to field of medicaments.

Claims

1. a kind of flat board mycin analog, it is characterised in that its structure such as formula (I), formula (II), formula (III), formula (IV) or formula (V) shown in：

Wherein, in formula (I), R is the alkyl of hydrogen or 1-10 carbon atom；R is preferably the alkyl of 1-6 carbon atom；R is preferably first Base, ethyl, n-propyl, normal-butyl；

In formula (II), Ar¹One kind in following structure：

X is hydrogen, fluorine, chlorine, bromine or iodine；R¹For hydrogen or methyl；R²For hydroxyl, amido or methoxyl group；R³For hydrogen or methyl；R⁴For hydrogen or Methyl；

In formula (III), Ar²For：Aromatic group, 2- thienyls, methyl, ethyl or n-propyl；The aromatic group is preferably benzene Base, 4- aminomethyl phenyls, 4- trifluoromethyls, 4- fluorophenyls, 4- chlorphenyls, 3- trifluoromethyls, 2- trifluoromethyls, 3- fluorophenyls, 2- fluorophenyls, 1- naphthyls, 2- naphthyls or 9- anthryls.

In formula (IV) and (V), n is:1-1000；Preferably 50-900, more preferably 500-800.

2. a kind of preparation method of flat board mycin analog, it is characterised in that the structural formula of the flat board mycin analog is as weighed During profit requires 1 shown in formula (I), its preparation method comprises the following steps：Using flat board mycin as raw material, using acid as catalyst, with water And/or alcohol is solvent, the compound of formula (I) in claim 1 is obtained by heating response, reaction equation is as shown in following formula eq.1：

3. preparation method as claimed in claim 2, it is characterised in that the catalyst is sulfuric acid, hydrogen chloride, fluoroform sulphur One or more in acid, p-methyl benzenesulfonic acid, acetic acid, aluminium chloride and hexafluorophosphoric acid copper；

Preferably, the reaction time of the heating response is more than 8 hours, preferably 8-20 hours, more preferably 10-15 hours；

Preferably, the mol ratio of flat board Mei Su ︰ Cuiization Ji ︰ solvents is 1.0:(0.001-0.5):(10-1000), preferred molar ratio For 1.0:(0.01-0.1):(100-500).

4. preparation method as claimed in claim 2, it is characterised in that the heating response temperature is 50-90 DEG C, preferably 60- 85 DEG C, preferably 75-80 DEG C；The solvent is the one or more in water, methanol, ethanol, normal propyl alcohol and n-butanol.

5. a kind of preparation method of flat board mycin analog, it is characterised in that the structural formula of the flat board mycin analog is as weighed During profit requires 1 shown in formula (II), its preparation method comprises the following steps：Using arylamine and flat board mycin acid as raw material, its reaction equation As shown in following formula eq.2：

6. preparation method as claimed in claim 5, it is characterised in that preferably, in formula eq.2, arylamine:Flat board mycin acid:2- (7- azos BTA)-N, N, N ', N '-tetramethylurea hexafluorophosphoric acid ester (HATU):The mol ratio of triethylamine is：(1.0- 5.0):1.0:(1.0-5.0):(3.0-6.0), preferred molar ratio are：(1.0-2.0):1.0:(1.0-2.0):(3.0-4.0)；

Preferably, in formula eq.2, catalyst is 2- (7- azos BTA)-N, N, N ', N '-tetramethylurea hexafluorophosphoric acid ester (HATU), dicyclohexylcarbodiimide (DCC), 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides (EDCI) or N, N'- DIC (DIC)；

Preferably, in formula eq.2, solvent is preferably in DMF, tetrahydrofuran, dichloromethane, chloroform One or more mixing.

7. a kind of preparation method of flat board mycin analog, it is characterised in that the structural formula such as right of flat board mycin analog will In asking 1 shown in formula (III), its preparation method comprises the following steps：Using flat board mycin and thiobenzoate and its derivative as original Material, its reaction equation is as shown in following formula eq.3：

Wherein, Ar²For：Aromatic group or 2- thienyls, methyl, ethyl, preferably n-propyl, phenyl, 4- aminomethyl phenyls, 4- tri- Trifluoromethylphenyl, 4- fluorophenyls, 4- chlorphenyls, 3- trifluoromethyls, 3,5- bis- trifluoromethyls, 2- trifluoromethylbenzenes Base, 3- fluorophenyls, 2- fluorophenyls, 1- naphthyls, 2- naphthyls, 9- anthryls.

8. preparation method as claimed in claim 7, it is characterised in that preferably, in formula eq.3, flat board mycin:Thio phenyl first Acid:The mol ratio of catalyst is：1.0:(1.0-5.0):(0.1-1.0), most suitable ratio are：1.0:(1.0-2.0):(0.1- 0.5)；Preferably, the reaction dissolvent in formula eq.3 is one in dichloromethane, chloroform, acetonitrile, acetone, ethyl acetate, water Kind is several；

Preferably, in formula eq.3, catalyst is triethylamine, diisopropyl ethyl amine (DIPEA), 1,8- diazabicylos 11 Any one of carbon -7- alkene (DBU), N-methylmorpholine, N, N- lutidines (DMAP) cesium carbonate, potassium carbonate, sodium carbonate.

9. a kind of preparation method of flat board mycin analog, it is characterised in that the structural formula such as right of flat board mycin analog will In asking 1 shown in formula (IV) and formula (V), synthetic route is according to such as formula eq.4 and as shown in formula eq.5, with flat board mycin sulfur-bearing chemical combination Thing is raw material, and its reaction equation is：

Wherein, n is the elementary cell repetition number of polyethylene glycol, n=1-1000, preferably 500-800.

Preferably, in formula eq.4, catalyst is triethylamine, diisopropyl ethyl amine (DIPEA), 1,8- diazabicylo 11 Carbon -7- alkene (DBU), N-methylmorpholine, N, N- lutidines (DMAP) and potassium carbonate；

Preferably, in formula eq.5, catalyst is general any catalyst that can produce univalent copper ion in click chemistry, Preferably copper sulphate, stannous chloride, cuprous bromide, cuprous iodide etc.；

Preferably, according to other similar connected modes, the reaction that flat board mycin is connected with polyethylene glycol and the flat board of acquisition are mould Plain polyethylene glycol compound.

10. application of the flat board mycin in terms of antibacterials are prepared described in claim 1.