TWI297009B - Structure of camphor-derived chiral auxiliary and the method for forming the same - Google Patents

Description

BRIEF DESCRIPTION OF THE DRAWINGS [Technical Field] The present invention relates to a structure of an asymmetric compound and a method for forming the same, and more particularly to a palm auxiliaries derived from a camphor structure and a method for forming the same. [Prior Art] According to Frost & Sulivan's report and forecast, the world's palm compound (product) market reached US$8.57 billion in 2004, and was about 3 billion US dollars in 2005. Oh, and with an average annual growth rate of U. 4%, it will reach about $1.5 billion in 2009. The palm chemical industry can be divided into two main categories: palm compound manufacturing and palm compound analysis. Among them, palm compound manufacturing dominates most markets and can be further subdivided into: inthesis and Chirai separation. Compared to chiral separati〇n, the market size is more exciting than (4) synthesis. In addition, in the pharmaceutical industry, according to the 2.3 years sales statistics report (extracted from "hidden AL OffiMISTW, Chemical & Engineering _ Story, June 14, 2004, Volume 82, Number 24, ρρ· 47-62), Formerly known as the world's most sold drugs, the active ingredients of nine drugs are palm-like. It is known that palm compounds play a very important role in the pharmaceutical industry.

By synthesizing the g of the integrator, it can catalyze the reaction of the lion and lion, and produce the high image transcendental value f' to prepare many pharmaceutical intermediate products. Well-known examples are: Monsanto's method developed by Kn〇wies (ws) to produce Z-D0PA 1297009 dihydrexyphenylM for Parkinson's Disease -alanine] 1 The basal ganglia in the brain of patients with Jinsen's disease lacks the precursor of 1⁄Z DQPA疋 dopamine, which can be catalyzed by enzymes to form dopamine. Therefore, Z DQPA can be used as a drug to treat Parkinson's disease. The research field developed by Nuo_, after more than 20 years of development, has gained great repercussions in the synthesis of organic chemistry. Chemists have succeeded in the development of hundreds of pairs of palm-integrating agents and catalysts, and their successful application to many different forms of organic reactions, relying heavily on the preparation of optical materials.

Catalyst, H2 NHAc

MeO

(95% ee) L-DOPA

AcO catalyst: [Rh(R, R)-DiPAMP)COD]+BF4~

H+

Another well-known method is the application of the ▲-branch rigid-structured palm-adhesive developed by 0pp〇lzer to the synthesis of optically active substances. For example, in a study by Bernard P. ROQUES et al. in 1995, 4-phosphonomethyl-phenylalanine (Pmp) was successfully prepared by the derivative of camphor sultam developed by 〇pp〇lzer. The phosphorylation and dephosphorylation of the tyrosine residues of proteins play an important role in cellular signal 1297009 transduction. These reactions are centrally regulated by proteins with tyrosine kinase (PTK) and phosphatase (PTP) catalytic activity, while abnormal expression of PTK and PTP leads to nepitest ceH transformation. Therefore, the development of the above-mentioned identifiable inhibitors (inhibit〇r) has attracted extensive attention. Through various studies to understand the signaling pathways in order to prepare potential anticancer drugs, the aforementioned studies can be performed using micropeptide bonds. Among them, the peptide bond is derived from the enzyme sequence surrounding the 0-phosphotyrosine residue, and the Pmp is a stable analog of the 〇- 咖 〇 ( (5) • residue. The stereoselectivity of the desired pmp can be controlled by the derivative of camphor siiltam developed by 0_lzer as shown in the following scheme.

9 1297009 The palm adjuvant has a significant and decisive influence on asymmetric chemical reactions. Because the price of the 对 掌 袼 is expensive and the synthesis method is complicated, if the recovery rate of the palm adjuvant can be improved, the low operating cost can be reused, and the environmental awareness of the draft can be met.爰疋 'How to synthesize an appropriate pair of auxiliary ships has become an important issue, and it is also a research and development direction that the industry has paid much attention to. SUMMARY OF THE INVENTION In order to meet the requirements of the industry, the present invention provides a new camphor-derived palm-assisted agent and a method for forming the same. The present invention is aimed at the secret of a silky touch of a silky body, introducing a group having a steric hindrance by a hydrazine derivative, and performing a cyclization process (bringing amines to manufacture-first-pair) The present invention is intended to be formed by the first pair of palm adjuvants and the absence of _, and the second pair of palm adjuvants are formed. Because of the formation method of the present invention The invention is simple and the product is selective and can obtain sufficient yield at the same time. Accordingly, the present invention can meet the economic benefits and the industrial utilization. According to the above purpose, the original meaning reveals that - scales _ Lai, Wei Xue The general formula (1) is as follows, wherein the _ group and the R 2 group are independent hydrogen atoms or alkyl groups having 1 to 10 carbon atoms, and the X group is an oxygen atom, two wind atoms or sulfur atoms. The Y group is a group having a steric obstacle. In addition, the present invention is also a method for forming a 1297009 palm adjuvant mainly based on the S (four) knowledge-type ageing sub-architecture.

[Embodiment] The invention is directed to the formation of the lion bottle by the __ brain structure. In order to be able to thoroughly understand the present invention, detailed process steps or constituent structures will be presented in the following description. In the face, the hair _ face is not a special fine g卩 familiar to the enemy. On the other hand, the public knowledge or process steps are not described in the details, so as to avoid unnecessary barriers to the gamma. The present _ 健 阙 阙 详细 详细 详细 详细 详细 详细 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 健 剌 剌. General (1) Ben: One of the structures of a pair of palm adjuvants,

1297009

Wherein the 'R® group and the R2®1 group are a hydrogen atom or a group having 1 JL of 1 G broken atoms, and the X group is an oxygen atom, two hydrogen atoms or a sulfur atom, and the above preferred R1 group The base is a hydrogen atom, and the ruthenium group is a methyl group, and preferably the oxime group is an oxygen atom. Next, a hydrazine derivative is provided, wherein the γ group is a group having a steric hindrance. The selection of the above γ group is the same as in the first embodiment. Then, a hydrazine derivative leg and a starting material are subjected to a dehydration process to form an imine compound (imi) compound, wherein the general formula of the above imine compound is as follows:

The equivalent number of the above hydrazine derivative hwnhy is greater than the above-mentioned dehydration process in dihalomethane (CH2C12) _ when the equivalent amount of the above starting materials is! When the above-mentioned hydrazine initial 1, the preferred equivalent number is about 1.2. Further, in the above dehydration solution, the operation temperature ranges from about 25 to 3 Torr. After the formation, a cyclization process is carried out so that the general formula of the imine compound described above is as follows: After the above-mentioned dehydration process is completed, the compound forms a brewing amine compound, wherein, the upper salty household 13 1297009

The V S匕 process is a one-pot reaction. In the preferred embodiment of the present embodiment, the above cyclization process may further comprise a hydrazine halogenation step and a (four) step, wherein the S ▲ self-catalyst step is carried out by reacting SQZ2 with an upper imine compound to form a middle portion. The composition, the mouth configuration is as follows, and the Z system is chlorine (ci), bromine (this) or ruthenium (I).

When the number of equivalents of the above imine compound is! When the amount of t is greater than 2, and the preferred number of miles is about 2.4. Further, in the above preferred embodiment, the above cyclization process is carried out in an ethyl acetate (EA) solution at an operating temperature range of about 5 Torr. . To 8〇 〇c. In this embodiment, after the cyclization process is completed, a reciprocating process is performed, and the above-mentioned guanamine compound reacts with the county ship to form a cis-pair _, and its chemical structure is general (I ) as follows: 1297009

In a preferred embodiment according to this embodiment, the reducing agent further comprises s〇dium cyanoborohydride (NaCNBIL.). When the number of equivalents of the above guanamine compound is 1, the number of equivalents of the above reducing agent is more than 15, and the preferred equivalent number thereof is about 18. Further, the above-mentioned reduction process is carried out in an acetic acid (AcOH) solution, and the operating temperature range is about throwing. c to 30 °C. EXAMPLE 1 Refer to scheme 1 and take (5)-camphorone decanoic acid [(+)-ketopinicacid] 1 (20. 00 g' lW76mm〇le), placed in a 500 ml double-necked round bottom bottle, add two Methane (15〇mL), stirred with magnet; after mixing until dissolved, force into the ^^〇luenesulf〇nhydrazi (je (MNH-Ts) (28. 62 g' 153·66 "unole), in the nitrogen system At room temperature (25 °C ~ 30 °C), stirring for about one hour / valley / night to clarify 'to stop the reaction with water, extract with dichloromethane, take the organic layer, remove water with anhydrous magnesium sulfate, filter, After slightly drying, the product was washed with n-hexane and methylene chloride 2-3 times, and concentrated under reduced pressure to give a white solid product 2, which was crystallised to give colorless transparent crystals (36. 54 g, yield 95%). !H NMR: 15 1297009 JH NMR (CDCla, 200 MHz) (57. 83 (d, /= 8. 4 Hz, 2H), Ί. 34 (d, 8· 2

Hz, 2H), 2.57 - 2.31 (m, 2H), 2.42 (s, 3H), 2.04 - 1·95 (m, 3H), l·66 (td, /= 9.8,3·6 Hz, 1H), 1-3. 134· 3, 130· 1,128·3, • 127·9,61· 1,51· 7,44 3,33· 9,31· 1,27.5,21· 5,19· 7 HRMS (high resolution mass spectrometry ): • Found: 350· 1283 (caicd for C17H22N2O4S 350.1300) Take compound 2 (9·00 g, 25.70 mmole) in a 1000 ml double-necked round bottom bottle 'ethyl acetate (EA) ( 660 mL of O, stir to dissolve with magnet, add 0SO0 (7·34 g, 61·69 mmole) to '60~80. (:, reflux for five hours, stop the reaction with water, then extract organic with ethyl acetate The layer is separated from water by anhydrous sulphuric acid, filtered, and reduced to dryness under reduced pressure. Purification by column chromatography, hexane : ethyl acetate = 3 · ί, 丄 _ °·1 horse extract, product 3 (6.66 g, yield 78%), recrystallized to give a clear, colorless crystal. !H NMR: $ NMR ( CDCL·, 200 MHz ) 5 7.87 (d, / = 7·4 Hz, 2H), 7·29 (d, / = 8 4

Hz, 2H), 2· 60 - 2· 51 (m, 1H), 2· 39 (s, 3H), 2· 25 - 2· 00 (m, 4H), j 6? 1297009 (td, /=9.8 , 3·4Ηζ, 1H), 1.45 (td, /=9.2, 3.8 Hz, 1H), 1.07 (s, 3H), 0.57 (s, 3H) 13C NMR: 13C NMR (CDCls, 200 MHz) 5176.2, 172.8, 145.2, 135.3, 129· 7, 127.9, 64.0, 50.9, 48.7, 32· 2, 26.8, 26.0, 2L 5,; 18.5, 18.1 i X-ray crystallographic analysis:

Crystal data for 3·Η2〇at 25〇C : C17H20N2O3S, M 332. 422, Orthorhombic, 10· 1101 (2) AK2· 9076 (3)A, 25· 9674 (8)A, P 3388· 67 (15)A,Z = 8,λ= 0.71073 A,A = 1·303 Mg/in3,# 二〇·21 Leg 1,2336 reflections, 416 parameters, R= 0.093, Rw- 0.096 for all data. HRMS (High Resolution Mass Spectrometry):

Found: 332.1190 (calcd for C17H20N2O3S 332.1195) Take compound 3 (4. 00 g, 12.04 mmole), place in a 500 ml round bottom flask, and add 60 ml of acetic acid (AcOH) to the magnet. Dissolve, in a nitrogen system, at room temperature (25 °C ~ 30 °C), (powdered NaCNBH3 (10) 62 g, 216 79 _le) into multiple batches, first add the first batch of NaCNBH3, and trace the reaction by thin layer chromatography To the extent that the first batch of powder was dissolved, a second batch of NaCNBIL· was added until all NaCNBH3 was added and dissolved. Then, a large amount of water was added to terminate the reaction, and the mixture was extracted with di-methane for 4 to 5 times. The organic layer was taken, and water was removed from anhydrous sulphuric acid, filtered, concentrated under reduced pressure to dryness, and purified by column chromatography to hexane: ethyl acetate = 2 : 1 As the extract, the product 4 (3.86 g, yield 96%) was obtained, and a clear colorless crystal was obtained by recrystallization. !Η NMR analysis: $ NMR ( CDCh, 200 MHz ) 57·94 (d, /= 8·4 Hz, 2H), 7·33 (d, / 2·8 Hz, 2H), 3.49 (dd, / = 8,4·4 Hz,1H),2.44 (s,3H),2.15 - 1.99 (m, ❿ 2H),1·90 - 1·80 (m, 2H),1·67 (dd, /= 13.2 , 8·4Ηζ, 1H), 1.29 - 1·16 (m, 2Η), 0·94 (s, 3Η), 0· 77 (s, 3Η) 13C NMR analysis: 13C NMR (CDCls, 200 MHz) 5172.4, 145.3, 134.7, 129.5, 128.6, 64.7, 59.0, 52.5, 47.2, 36.4, 29.0, 26.5, 21.6, 20.5, 19.7 • X-ray crystallographic analysis:

Crystal data for pps-1 ·Μ) at 25°C: C17H22N2O3S, C17H22N2O3S, #334.438, * Monoclinic, P2h 5= 9.7297 (3)A, b= 14.6999 (4)A, c- 12.2705 (5)A, _ F= 1714.77 (10)A3, ^ = 4, D, = 1.295 Mg/ra3, β - 0.205 ram'1, 5864 reflections, 415 parameters, R= 0.0999, 0,1829 for all data. HRMS (High Resolution Mass Spectrometry) :

Found: 334· 1350 (calcd for C17H22N2O3S 334· 1351) 1297009

SCHEME 1 A third embodiment of the present invention discloses a structure of a palm adjuvant, the chemical structure of which is generally as follows:

(π) R1 wherein the R1 group and the R2 group are independent hydrogen atoms or the alkyl group having 1 to 10 carbon atoms is an oxygen atom, two hydrogen atoms or a sulfur atom. The above preferred R1 group is a hydrogen atom, and 1297009 preferably the R2 group is a methyl group, and preferably the X group is an oxygen atom. A fourth embodiment of the present invention discloses a method of forming a palm adjuvant. First provide a starting object, the general formula of the starting material is as follows:

Wherein the R1 group and the R2 group are independent hydrogen atoms or an alkyl group having 1 to 10 carbon atoms, and the X group is an oxygen atom, two hydrogen atoms or a sulfur atom, and the above preferred R1 group The base is a hydrogen atom, preferably the R2 group is a methyl group, and preferably the X group is an oxygen atom. Next, a hydrazine derivative IfcNNHY is provided, wherein the Y group is a group having a steric hindrance. The selection of the above Y group is the same as that of the first embodiment. Then, a dehydration process is carried out by the hydrazine derivative leg NHY and the starting material to form an imine compound, wherein the general formula of the above imine compound is as follows:

The equivalent number of the starting material of the field is one leaf, and the equivalent number of the above hydrazine derivative 沁nnhy is more than 1 ', and the preferred equivalent number is about 1.2. In addition, the above-described dehydration process is carried out in a two-gas calcination (CH2Cl2) solution at an operating temperature range of about 25 ° C to 30 ° C. 20 1297009 In the present embodiment, after the above-described dehydration process is completed, a cyclization process is carried out to form an imine compound to form a guanamine compound, wherein the general formula of the above guanamine compound is as follows:

The above cyclization process is a one-pot reaction. In a preferred embodiment of the present embodiment, the cyclization process may further comprise a hydrazine halogenation step and a dehalogenation step, wherein the 醯-chemification step is carried out by reacting S0Z2 with the imine compound described above to form An intermediate having the structural formula is as follows 'and the Z system is gas (C1), actor (Br) or yttrium (I).

When the number of equivalents of the above imine compound is 1, the equivalent number of foxes is more than 2, and the number of succinct is preferably about 2.4. Further, in the above preferred embodiment, the above cyclization process is carried out in an ethyl acetate (EA) solution at an operating temperature in the range of about 5 Torr to (9). c. In this embodiment, after the completion of the cyclization process described above, a reduction process is performed, and the above-mentioned amide amination and the reduction of the ship are reacted to form a first-to-the-palm adjuvant, the chemical structure of which is generally Formula (I) is as follows: 1 21 1297009

Then 'by the first-to-palm 嶋----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- (triethylamine, EhN) 'and the general formula of the second pair of palm adjuvants described above is as follows:

In a preferred embodiment according to this embodiment, the reducing agent further comprises s〇dium cyanoborohydride (NaCNBIL.). When the number of equivalents of the above guanamine compound is 1, the above-mentioned reducing agent has a number of turns of more than 15, and its preferred equivalent number is about μ. In addition, the above reduction process is carried out in an acetic acid (AcOH) solution at an operating temperature range of about 25 to 30 t: 〇〇EXAMPLE 2 as shown in Scheme 2, taking (3)-camphor _ citrate [(1)_ket〇 Pinic acid] i (2〇· 〇〇g, 109· 76 mmole), placed in a 500 ml double-necked round bottom bottle, add two methane (15 〇), 22 1297009 stir with a magnet until dissolved, add ^^〇luenesulf〇nhy(jrazi(ie (H2NNH-Ts) (28.62 S' ^3.66 mm〇le), under nitrogen system, at room temperature (25 〇c~3〇. 〇, stirring for about one hour after solution change) Clarification, adding water to terminate the reaction, extracting with dichloromethane, taking the organic layer, removing water with anhydrous barium sulfate, filtering, slightly drying, washing the product with hexane and di-methane for 2-3 times, and concentrating to dryness under reduced pressure. The product 2 is obtained as a white solid. After recrystallization, colorless transparent crystals (36. 54 g, yield 95%) are obtained. 〇 _ Take compound 2 (9· 〇〇g, 25·70 _le), placed in a 1000 ml double neck Add ethyl acetate (ethyl acetate, EA) (660 mL) to a round bottom flask, stir to dissolve with magnet, and add S0C12 (7·34). g, 61·69 mmole), heated to 60-80 ° C, refluxed for five hours, the reaction was quenched with water, then the organic layer was extracted with ethyl acetate, and water was removed with anhydrous sulphuric acid, filtered, and concentrated to dryness Purification by column chromatography, using hexane : ethyi acetate = 3 : 1 as the extract, product 3 (6·66 g, yield 78%), recrystallized to obtain transparent colorless crystals. 00 g,12·04 mmole), placed in a 500 ml round bottom bottle, add 60 ml of acetic acid (aceticacid; Ac〇iQ, stir to dissolve with magnet, under nitrogen system, room temperature (25 °C~30) 〇, (Part the powdered NaCNBH3 (13.62 g, 216.79 mmole) into multiple batches 'first add the first batch of NaCNBH3' and analyze the degree of the tracer reaction by thin layer chromatography. After the first batch of powder is dissolved, add the first Two batches of NaCNBIfc were added until all NaCNBH3 was added and dissolved. Then, a large amount of water was added to terminate the reaction, and the mixture was extracted with di-methane for 4-5 times. The organic layer was taken, water was removed with anhydrous magnesium sulfate, and filtered under reduced pressure to dryness. Purified by column chromatography to hexane · ethyl 23 1297009 etate 2 . As a liquid extract, the product 4 (3 86 & coffee 1 (1 96%) was obtained, and a clear colorless crystal was obtained by recrystallization. S,5·99 mm〇ie), placed in a 1 〇〇 double neck round bottom bottle, take compound 4 (2· 〇〇

Add two gas to the fine mL), add magnetic acid to dissolve and add triethylamine (1) U π surface (6). Under nitrogen, at room temperature, after 12 hours, the reaction is complete, and the reaction is terminated by adding water. The organic layer was taken, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness to give a white solid product 5' recrystallized to give colorless crystals (1.Q1 g, 95%). !h nmr: !OMR ( CDCh, 200 MHz ) δ8·56 (bs, 1H), 2·62 (ddd, /Μ7·6, 4 0 2·6 Hz, 1H), 2·36 - 2·05 ( m,4H),1·73 (td,/= 9.9,3·7 Hz,1H) 1·5 (td, / 2·8·4·9 Hz, 1H), 1·22 (s, 3H) , 0.97 (s, 3H) _ 13C NMR: 13C 臓 (CDCh, 200 MHz) 5 176.7, 175.5, 62,5, 49.7, 49·4, 32· 〇, 26· 9 25,3, 19.0, 18.5 X- Ray crystallographic analysis:

Crystal data for Compound 5 · H2O at -73 °C : C10H16N2O2, m 196 25, Orthorhombic, P2i2i2i, a = 6. 7310(2) A, 11. 5370(4) A, 0=13 3580(6) A, 7= 1037·32(7) A3, 4, A = 1·257 Mg/m3, // = 0·〇88 mm-, 1788 24 1297009 reflections, 128 parameters, 0.0564, 0.1314 for all data.

3

Et3N -^ ch2ci2 N2, r.t., 12 hr 4

H SCHEME 2 25 5 l297〇〇9 In the above-described examples of the present invention, the object of the present invention is to introduce a group having steric hindrance by using a readily available rod brain derivative as a raw material by a Wrazine derivative. The base is subjected to a cyclization process (amylamine) to produce a palm adjuvant. This is because the method of formation of the present invention is simple, the product selectivity is high, and at the same time, sufficient freshness is obtained. Accordingly, the present invention can meet economic benefits and industrial applicability. In summary, the present invention discloses two pairs of palm adjuvants whose chemical structures are generally as shown in the following formulae (1) and (H), wherein the R1 group and the r2 group are independent hydrogen atoms or have! The alkyl group is an oxygen atom, two hydrogen atoms or a sulfur atom, and the γ group is a group having a steric hindrance.

Obviously, the present invention may have many modifications and differences in light of the above description. It is therefore to be understood that within the scope of the appended claims, the invention may be The above is only the preferred embodiment of the present invention, and the patent modification or modification performed in the spirit of the other inventions of the invention is included in the following patents. Within the scope. 26

Claims (1)

曰修(more) Original, the scope of application for patent: U _ month Seed-to-palm aids The general formula of the pair of palm adjuvants is as follows: Wherein, the R1 group and the R1 2 3 group are mono- or A-clay groups having 1 to 10 carbon atoms are oxygen atoms, two disks I are two Langzi or sulfur atoms, and the Y group is - a steroid with steric hindrance, selected from one of the following groups: 0 1 Z1 Π Horse system ^ from the following groups: hydrogen atom, methyl, gas atom, bromine atom, iodine atom, nitrile f nitrite group (mtnle group), ether group, amine group, nitro group, Z2 Phenyl group and propylene group (aUyi_p). 27 1 is selected from the following groups: methyl and isopropyl 2 2. For example, please refer to #_, the preferred one of the above 3 / ^ tolunesulfonyl, the structural formula is as follows 1297009 - a method for forming a pair of palm adjuvants, the method for forming the palm adjuvant comprising providing a starting material, the general formula of the starting material is as follows: R2 Wherein the R group and the R group are independent hydrogen atoms or the alkyl group having 1 to carbon atoms is an oxygen atom, two hydrogen atoms or a sulfur atom; providing a hydrazine derivative (hydrazine) Derivative) H2 Li HY, wherein the Y group is a group with steric hindrance, which is selected from one of the following groups: .z1 (1) 〇U 4 is selected from one of the following groups: hydrogen atom, methyl group, gas atom, shoulder atom, argon atom, nitrile group, mystery group, amine group, nitro group, phenyl group ( Phenyl group) with propylene (allyl gmjp). Z2 Z2, Z is selected from one of the following groups: methyl and isopropyl; by the Wei toucher MMY touches the rugged-financial compound, the imine compound, wherein the imine compound The general formula is as follows; 28 1297009 Performing a cyclization process to form the imine compound into a monoamine compound, wherein the general formula of the guanamine compound is as follows; The pair of palm-assisted swords are formed by the _compound and-reduction ship-reduction process, wherein the general formula of the pair of palm adjuvants is as follows. 4. The group system of the palm adjuvant as described in item 3 of the patent application scope is p-tolunesulfony, and its structural formula is as described above. 29 1297009 5. If the method of forming the above-mentioned starting material is 1, the equivalent number of the hydrazine derivative Η2ΝΝΗΥ is greater than i. 6. If the application of the special fiber (4) 5 is described as the auxiliary assistance, the preferred equivalent number of the above-mentioned combined gas derivative IfcNNHY is about 丨.2. 7. 7. (4) The method of forming the third job of the special fiber circumference, wherein the above-mentioned dehydration process is carried out in a dichloromethane (cmci2) solution. -8. The method of forming a palm adjuvant as described in claim 3, wherein the dehydration process has an operating temperature range of about 25 ° C to 30 ° C. 9. The method as claimed in claim 3, wherein the above-described cyclization process further comprises a step of 醯- and a step of removing. 10. If the application method of the transfer assistance method described in item 3 of the special design is applied, the above-mentioned cyclization process is a one-pot reaction. Π········································································ The formula is as follows and the Z system is gas (C1), bromine (Br) or iodine (I). When the number of equivalents of the method for forming a palm adjuvant as described in the above-mentioned imidization of the invention is 1, the number of equivalents of the s〇z2 is more than 2. 13. The application of the above-mentioned (10) is preferably about 2.4. 14. The method for forming a counter-rotation as described in claim 3, wherein the cyclization process is carried out in an ethyl acetate (EA) solution. 15. If you apply for the third item of the riding aid, the county green, the operating temperature range of the above-mentioned cyclization process is about 50 °C to 80 t. The method of forming a palm adjuvant as described in claim 3, wherein the reducing agent further comprises sodium cyanoborohydride (NaCNBHs). 17. The method for forming a palm adjuvant according to claim 3, wherein when the number of equivalents of the above-mentioned alanated 31 1297009 is 1, the method for forming the equivalent of the reducing agent is greater than π, wherein Reduction 18. The preferred equivalent weight of the palm adjuvant as described in claim 17 is about 18. 19. The method as claimed in claim 3, wherein the reduction process is carried out in an acetic acid (AcOH) solution. 20. The method of forming a palm adjuvant as described in claim 3, wherein the above-mentioned reduction process has an operating temperature range of about 25 ° C to 30 t. 21. A method for forming a lining aid, the method for forming a palm assisted lie comprising: providing Woluenesulfonhydmzide (H2__Ts) and (3) _ camphor ketone citrate [(+)-ketopinic acid], the structural formula of which is as follows; 〇H in a solution of methylene chloride (cm: 2), a dehydration process is carried out by H2NNH_Ts and ((+)-ketopinic acid] to form an imine compound, wherein The structural formula of the imine compound is as follows; 32 1297009 In acetic acid (10) (10) fine her, EA) Xie, ♦ ringing amine compounds form a guanamine compound, wherein, 卞, the general formula of the guanamine compound is Κ / Λ Λ / Λ y y The Ts is in an acetic acid (brush) solution, and the guanamine compound is subjected to a reduction process to form the pair of palm adjuvants, wherein the pair of palm adjuvants are the fun & swordsmanship Me, JVie ° 22. The method for forming a palm adjuvant as described in claim 21, when the upper part is (the number of equivalents of [(1)-ketopinic acid], the 樟 is about 1.2. 33 1297009 'The above-mentioned dehydration 23 · The process for forming the palm auxiliaries as described in claim 21 of the patent application range is about 25 ° C to 30 ° C. 24 · If the patent application scope is 21 The method for forming a palm adjuvant as described in the above, wherein the above-mentioned strictening process is a one-pot reaction (one-pot reacti), and comprises - 醯 = 牛..., milk step. The method of forming a method according to the item of item 24, wherein the step of reacting with the imine compound by S0C12 forms an intermediate, wherein the structural formula of the intermediate is as follows. 26. The method for forming a palm adjuvant as described in claim 25, wherein when the number of equivalents of the imine compound is 1, the equivalent number of the SOC12 is about 2.4. & For the method of forming the lion as described in Item 21 of the application, the operating temperature range of the above-mentioned cyclization process is about 50 ° C to 80 t. 34.1297009 28. The method for forming a palm adjuvant according to claim 21, wherein the reducing agent further comprises sodium cyanoborohydride (NaCNBHs) 〇 29. as described in claim 28 The method of forming the auxiliary agent, #################################################################################################### The method for forming a palm adjuvant, wherein the above-mentioned reduction process has an operating temperature range of about 25 t to 30 t. 31· a pair of palm adjuvants, the general formula of the palm adjuvant is as follows: N I 烷 to 10 carbon atoms of the alkane wherein the group of the group and the group of the group R2 are independently a hydrogen atom or have a group, and the group of the group X is an oxygen atom, two hydrogen atoms or a sulfur atom. - Kind of palm _ decorated her, the _ aid axis into the method contains. Provide a wide t〇lUenesulfonhydrazid acid [(1) she is fine, its structural style zen brain shouting 35 02. 1297009 OH is dehydrated in a solution of dichloromethane (CH2Ch) by h2NNH-Ts and (5)-camphorone decanoic acid [(+)-ketopinic acid] to form an imine compound, wherein The structural formula of the imine compound is as follows; In a solution of ethyl acetate (EA), a cyclization process is carried out to form the imine compound into a monoamine compound, wherein the general formula of the guanamine compound is as follows; In an acetic acid 'AcOH solution, a reducing process is carried out by a saftamine compound and a reducing agent to form the first-to-palm adjuvant. The general formula of the first-to-palm adjuvant is as follows; 1297009 Forming a second pair of palm adjuvants in the dioxane methane (CH2Cl〇 solution by the first pair of palm adjuvants and triethylamine (EtsN), wherein the second pair of palms The structural formula of the adjuvant is as follows.