CN111233713A - Synthesis method of telavancin intermediate - Google Patents
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- CN111233713A CN111233713A CN202010063868.1A CN202010063868A CN111233713A CN 111233713 A CN111233713 A CN 111233713A CN 202010063868 A CN202010063868 A CN 202010063868A CN 111233713 A CN111233713 A CN 111233713A
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Abstract
The invention discloses a synthesis method of a telavancin intermediate, which takes N-decanol and aminoethanol as starting materials, and obtains N- (9-fluorenylmethoxycarbonyl) decylamineacetaldehyde through condensation, Fmoc-Cl amino protection and oxidation.
Description
The technical field is as follows:
the invention belongs to the technical field of medicines, and particularly relates to a synthesis method of a telavancin intermediate.
Background art:
telavancin is a novel lipoglycopeptide antibiotic, a new drug developed jointly by Shiwang, USA (Theravance) and Anthras, Japan (Astelas). FDA was approved in us for the treatment of skin infections caused by gram-positive bacteria in 2009, and EMA was approved in 2011 for the treatment of adult hospital-acquired pneumonia caused by MRSA. The activity of telavancin on MRSA, MRSE and the like is higher than that of vancomycin, the half-life period is longer than that of vancomycin, and clinical administration is carried out once a day. The super bacteria is caused by the abuse of antibiotics for human beings, the super bacteria is multi-drug resistant bacteria, the antibiotic drugs in the market have no treatment effect on the super bacteria, and telavancin has anti-drug resistance, is used for infection caused by sensitive bacteria for a long time, has definite curative effect, is an important drug for anti-infective therapy and has wide market prospect.
In the prior patent US7074890, 2-decylaminoethanol is used as a starting material, N-Fmoc-2- (decylamino) ethanol is obtained by protecting amino with Fmoc-Cl, and N- (9-fluorenylmethoxycarbonyl) decylaminoethylaldehyde is obtained by Swern oxidation at-40 ℃ with dichloromethane as a solvent DMSO/oxalyl chloride.
The prior patent WO03018607 uses decanal and ethanolamine as principles, and adopts amination reduction to obtain 2- (N-decylamino) ethanol, Fmoc-Cl protection and Swern oxidation to obtain N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde, and the same problems exist in the above patent.
In addition, another investigator, Cao Sheng, et al, uses decylamine and aminoacetaldehyde dimethyl acetal as starting materials, and obtains N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde through reductive amination, Fmoc-Cl protection and hydrochloric acid hydrolysis, the reaction is easy to control, but the starting materials decylamine and aminoacetaldehyde dimethyl acetal are more expensive.
In conclusion, the N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde is an important intermediate for synthesizing telavancin, and has great significance in preparation and synthesis.
The invention content is as follows:
aiming at the problems, the technical problem to be solved by the invention is to provide a synthesis method of a telavancin intermediate, which comprises the following steps:
(1) dissolving n-decanol in dichloromethane at normal temperature, adding organic base 1, dropwise adding methanesulfonyl chloride, and reacting for 12 h;
(2) adding the reaction solution after reacting for 12 hours into ice water, layering, and concentrating to obtain a concentrated solution 1;
(3) dissolving the concentrated solution 1 with ethanol, adding organic base 2, adding aminoethanol, and heating to react for 24 h;
(4) adding dichloromethane and water into the reaction solution after the temperature rise reaction for 24 hours, extracting, and concentrating to obtain a concentrated solution 2;
(5) dissolving the concentrated solution 2 by using dichloromethane, adding organic base 3 and Fmoc-Cl, controlling the temperature of the reaction solution to be not more than 25 ℃, and reacting for 4 hours;
(6) adding the reaction solution after reacting for 4 hours into water, layering, washing an organic layer once by using a sodium bicarbonate aqueous solution, and concentrating to obtain a concentrated solution 3;
(7) dissolving the concentrated solution 3 in dichloromethane, adding an aqueous solution of TEMPO and potassium bromide, controlling the pH value of the reaction solution at a certain value, controlling the reaction temperature, and dropwise adding sodium hypochlorite for oxidation reaction;
(8) after the reaction, the layers were separated, and the organic layer was washed with an aqueous sodium bicarbonate solution, dried and concentrated to obtain N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde.
Preferably, the organic base 1 is triethylamine, N-diisopropylamine or pyridine, preferably triethylamine.
Preferably, the organic base 2 is triethylamine, N-diisopropylamino or pyridine, preferably N, N-diisopropylamino.
Preferably, the ratio of the aminoethanol to the concentrated solution 1 in the step 3) is 1-20, preferably 10/1, and the reaction temperature is 0-100 ℃, preferably 80-90 ℃.
Preferably, the organic base 3 is triethylamine, N-diisopropylamino or pyridine, preferably N, N-diisopropylamino.
Preferably, the reaction temperature in the step (5) is not higher than 25 ℃, and is preferably-5-0 ℃.
Preferably, in the step (7), the reaction temperature is controlled to be-10-25 ℃, preferably-5-0 ℃, the reaction pH is controlled to be 7-12, and preferably the reaction pH is 8-9.
Preferably, the concentration of sodium hypochlorite in the step (7) is 10%, and the reaction is detected by TLC.
The invention has the beneficial effects that: the materials such as n-decanol, aminoethanol, methylsulfonyl chloride and the like involved in the synthesis are low in price, and the synthesis cost is greatly reduced. High synthesis yield, less side reaction, simple operation of each synthesis step, simple subsequent treatment and environmental protection. TEMPO oxidation condition is mild, pH value and reaction temperature of reaction liquid are controlled, aldehyde can be selectively oxidized, reaction condition is easy to control, and subsequent treatment is simple.
Description of the drawings:
FIG. 1 is a schematic diagram of the synthesis method of the present invention.
The specific implementation mode is as follows:
in order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described below with specific embodiments and accompanying drawings. It is to be understood that such description is merely illustrative and not intended to limit the scope of the present invention. Moreover, in the following description, descriptions of well-known structures and techniques are omitted so as to not unnecessarily obscure the concepts of the present invention.
As shown in fig. 1, the method for synthesizing a telavancin intermediate in this embodiment aims to provide a method for synthesizing a telavancin intermediate, N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde: n-decanol and aminoethanol are used as starting materials, and N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde is obtained by condensation, Fmoc-Cl amino protection and oxidation, 2,6, 6-tetramethylpiperidine oxide (TEMPO) is selected as an oxidant, the reaction temperature is below 0 ℃, dichloromethane is used as a solvent, and primary alcohol is selectively controlled to be oxidized into aldehyde, wherein the method comprises the following steps:
(1) dissolving n-decanol in dichloromethane at normal temperature, adding organic base 1, dropwise adding methanesulfonyl chloride, and reacting for 12 h;
(2) adding the reaction solution after reacting for 12 hours into ice water, layering, and concentrating to obtain a concentrated solution 1;
(3) dissolving the concentrated solution 1 with ethanol, adding organic base 2, adding aminoethanol, and heating to react for 24 h;
(4) adding dichloromethane and water into the reaction solution after the temperature rise reaction for 24 hours, extracting, and concentrating to obtain a concentrated solution 2;
(5) dissolving the concentrated solution 2 by using dichloromethane, adding organic base 3 and Fmoc-Cl, controlling the temperature of the reaction solution to be not more than 25 ℃, and reacting for 4 hours;
(6) adding the reaction solution after reacting for 4 hours into water, layering, washing an organic layer once by using a sodium bicarbonate aqueous solution, and concentrating to obtain a concentrated solution 3;
(7) dissolving the concentrated solution 3 in dichloromethane, adding an aqueous solution of TEMPO and potassium bromide, controlling the pH value of the reaction solution at a certain value, controlling the reaction temperature, and dropwise adding sodium hypochlorite for oxidation reaction;
(8) after the reaction, the layers were separated, and the organic layer was washed with aqueous sodium bicarbonate, dried and concentrated to give N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde without further purification.
Specifically, in the step (1), the organic base 1 can be triethylamine, N, N-diisopropylamine, pyridine and the like, preferably triethylamine, and pyridine has large toxic and side effects and is expensive.
The organic base 2 in the step (3) can be triethylamine, N, N-diisopropylamine, pyridine and the like, and preferably N, N-diisopropylamine; the ratio of the aminoethanol to the concentrated solution is 1-20, preferably 10/1, the aminoethanol is too high, on one hand, the material waste is caused, on the other hand, the aminoethanol is not completely treated in the washing step and also participates in oxidation in the oxidation step, and when N- (9-fluorenylmethoxycarbonyl) decylamineacetaldehyde and vancomycin are subjected to butt joint, the aminoacetaldehyde also participates in butt joint reaction, so that impurities are generated; the reaction temperature is 0-100 ℃, preferably 80-90 ℃.
The organic base 3 in the step (5) can be triethylamine, N, N-diisopropylamine, pyridine and the like, and preferably N, N-diisopropylamine; the reaction temperature is not higher than 25 ℃, and preferably-5-0 ℃.
In the step (7), the reaction temperature is controlled to be-10-25 ℃, and is preferably-5-0 ℃; the reaction pH is controlled to be 7-12, and the preferable pH is 8-9. In the step (7), the concentration of sodium hypochlorite is required to be 10%, TLC is used for reaction detection, and the reaction can be stopped by dropwise adding equivalent sodium hypochlorite.
Example 1 synthesis of N-decylaminoethanol:
adding 8g (50mmol) of n-decanol into a three-necked bottle, stirring and diluting 25ml of dichloromethane, adding 4g (59mmol) of triethylamine, controlling the reaction temperature to be 0 ℃, dropwise adding 8g (70mmol) of methanesulfonyl chloride, after the dropwise addition is finished, heating to room temperature, and reacting for 12 hours. After TLC (iodine fumigation) detection reaction, adding ice water, layering, collecting an organic layer, drying with sodium sulfate, and concentrating to obtain concentrated solution 1, which can be used for the next reaction without purification. Dissolving the concentrated solution 1 in 30ml of absolute ethanol, transferring the solution to a three-necked bottle, adding 30g (0.5mol) of aminoethanol, slowly heating to 90 ℃, and reacting for 12 hours. 100ml of methylene chloride and 100ml of water were added, layers were separated, and the organic layer was dried over sodium sulfate and concentrated to obtain a concentrated solution 2, which was subjected to the next reaction without purification.
Example 2 synthesis of N-decylaminoethanol:
adding 8g (50mmol) of n-decanol into a three-necked bottle, stirring and diluting 25ml of dichloromethane, adding 4g (59mmol) of triethylamine, controlling the reaction temperature to be 0 ℃, dropwise adding 8g (70mmol) of methanesulfonyl chloride, after the dropwise addition is finished, heating to room temperature, and reacting for 12 hours. After TLC (iodine fumigation) detection reaction, adding ice water, layering, collecting an organic layer, drying with sodium sulfate, and concentrating to obtain concentrated solution 1, which can be used for the next reaction without purification. Dissolving the concentrated solution 1 in 30ml of absolute ethanol, transferring the solution to a three-necked bottle, adding 60g (1mol) of aminoethanol, slowly heating to 90 ℃, and reacting for 12 hours. 100ml of methylene chloride and 100ml of water were added, and the layers were difficult to separate without conducting the next reaction.
Example 3 Synthesis of N- (9-fluorenylmethoxycarbonyl) -N-N-decylaminoethanol:
9.3g (41.2mmol) of decylaminoethanol and 7.2ml of DIPEA are added into a three-neck flask, 30ml of dichloromethane is added into the three-neck flask, the temperature is controlled to be not higher than 0 ℃, dichloromethane solution of Fmoc-Cl (9.4g of Fmoc-Cl, 37.2mmol and 10ml of dichloromethane) is added dropwise, reaction is carried out for 2 hours at the temperature of 0 ℃ after the dropwise addition is finished, 200ml of saturated sodium bicarbonate aqueous solution is added after the reaction is finished, the layers are separated, an organic layer is washed once by dilute hydrochloric acid, dried by sodium sulfate and concentrated to obtain concentrated solution 3.
Example 4 synthesis of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde:
dissolving 10g N- (9-fluorenylmethoxycarbonyl) -N-Fmoc-Cl-aminoethanol (23.6mmol) in 200ml of dichloromethane, adding 100ml of purified water, adding 10.2g of sodium bicarbonate, adjusting the pH of a reaction solution to about 8.5, adding 0.4g (3.4mmol) of potassium bromide and 0.1g of TEMPO, cooling the temperature of the reaction solution to-5 ℃, dropwise adding 40ml of sodium hypochlorite, after the dropwise addition, detecting by TLC (thin layer chromatography), layering, extracting an aqueous layer once with 100ml of dichloromethane, combining organic layers, washing once with saturated sodium carbonate aqueous solution, washing once with saline, drying, concentrating to obtain light yellow oily substances, adding 100ml of N-hexane, stirring, freezing, and crystallizing to obtain an off-white solid, namely, N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde was found to be about 8.5g, and the yield was 85%.
Example 5 Synthesis of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde:
dissolving 10g N- (9-fluorenylmethoxycarbonyl) -N-Fmoc-Cl-aminoethanol (23.6mmol) in 200ml of dichloromethane, adding 100ml of purified water, adding 10.2g of sodium bicarbonate, adjusting the pH of the reaction solution to about 10, adding 0.4g of potassium bromide (3.4mmol) and 0.1g of TEMPO, cooling the temperature of the reaction solution to-5 ℃, dropwise adding 40ml of sodium hypochlorite, after the dropwise addition, detecting the completion of the reaction by TLC (producing much N- (9-fluorenylmethoxycarbonyl) decylaminoacetic acid), carrying out layering, extracting the water layer once with 100ml of dichloromethane, combining the organic layers, washing once with saturated aqueous sodium carbonate solution, washing once with saline solution, drying, concentrating to obtain pale yellow oily matter, adding 100ml of N-hexane, stirring, freezing, and crystallizing to obtain a white-like solid, namely about 3.6g of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde, the yield thereof was found to be 36%.
Example 6 Synthesis of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde:
dissolving 10g N- (9-fluorenylmethoxycarbonyl) -N-Fmoc-Cl-aminoethanol (23.6mmol) in 200ml of dichloromethane, adding 100ml of purified water, adding 10.2g of sodium bicarbonate, adjusting the pH of the reaction solution to about 8.5, adding 0.4g (3.4mmol) of potassium bromide and 0.1g of TEMPO, cooling the temperature of the reaction solution to 10 ℃, dropwise adding 40ml of sodium hypochlorite, after the dropwise addition, detecting the completion of the reaction by TLC (producing much N- (9-fluorenylmethoxycarbonyl) decylaminoacetic acid), carrying out layering, extracting the water layer once with 100ml of dichloromethane, combining the organic layers, washing once with a saturated sodium carbonate aqueous solution, washing once with saline, drying, concentrating to obtain a pale yellow oily substance, adding 100ml of N-hexane, stirring, freezing, and crystallizing to obtain a white-like solid, namely about 4.3g of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde, the yield thereof was found to be 43%.
Example 7 Synthesis of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde:
10g N- (9-fluorenylmethoxycarbonyl) -N-Fmoc-Cl-aminoethanol (23.6mmol) was dissolved in 200ml of dichloromethane, 100ml of purified water was added, 10.2g of sodium bicarbonate was added, the pH of the reaction solution was adjusted to about 8.5, 0.4g of potassium bromide (3.4mmol) and 0.1g of TEMPO were added, the temperature of the reaction solution was cooled to-5 ℃, 80ml of sodium hypochlorite was added dropwise, the completion of the addition was detected by TLC (complete formation of N- (9-fluorenylmethoxycarbonyl) decylamineacetic acid and absence of N- (9-fluorenylmethoxycarbonyl) decylamineacetaldehyde), the reaction failed, and no post-treatment was performed.
Example 8 Synthesis of N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde:
dissolving 100g N- (9-fluorenylmethoxycarbonyl) -N-Fmoc-Cl-aminoethanol (0.24mol) in 2000ml of dichloromethane, adding 1000ml of purified water, adding 102g of sodium bicarbonate, adjusting the pH of the reaction solution to about 8.5, adding 4g (34mmol) of potassium bromide and 1g of TEMPO, cooling the temperature of the reaction solution to-5 ℃, dropwise adding 400ml of sodium hypochlorite, after the dropwise adding, detecting the reaction by TLC, layering, extracting the water layer once with 1000ml of dichloromethane, combining the organic layers, washing once with a saturated sodium carbonate aqueous solution, washing once with a saline solution, drying, concentrating to obtain light yellow oily matter, adding 1000ml of N-hexane, stirring, freezing, and crystallizing to obtain a white-like solid, namely, N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde was found to be present in an amount of about 92.4g, and the yield was found to be 92.4%.
The invention provides a method for synthesizing telavancin intermediate N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde, which comprises the steps of taking N-decanol and aminoethanol as starting materials, carrying out condensation, Fmoc-Cl amino protection, and oxidizing to obtain the N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde. The invention selects 2,2,6, 6-tetramethyl piperidine oxide (TEMPO) as an oxidant, the reaction temperature is below 0 ℃, dichloromethane is used as a solvent, and primary alcohol is selectively controlled to be oxidized into aldehyde.
The foregoing shows and describes the basic principles and principal features of the invention, together with the advantages thereof. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are given by way of illustration of the principles of the present invention, and that various changes and modifications may be made without departing from the spirit and scope of the invention as defined by the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (8)
1. A synthesis method of a telavancin intermediate is characterized by comprising the following steps: the method comprises the following steps:
(1) dissolving n-decanol in dichloromethane at normal temperature, adding organic base 1, dropwise adding methanesulfonyl chloride, and reacting for 12 h;
(2) adding the reaction solution after reacting for 12 hours into ice water, layering, and concentrating to obtain a concentrated solution 1;
(3) dissolving the concentrated solution 1 with ethanol, adding organic base 2, adding aminoethanol, and heating to react for 24 h;
(4) adding dichloromethane and water into the reaction solution after the temperature rise reaction for 24 hours, extracting, and concentrating to obtain a concentrated solution 2;
(5) dissolving the concentrated solution 2 by using dichloromethane, adding organic base 3 and Fmoc-Cl, controlling the temperature of the reaction solution to be not more than 25 ℃, and reacting for 4 hours;
(6) adding the reaction solution after reacting for 4 hours into water, layering, washing an organic layer once by using a sodium bicarbonate aqueous solution, and concentrating to obtain a concentrated solution 3;
(7) dissolving the concentrated solution 3 in dichloromethane, adding an aqueous solution of TEMPO and potassium bromide, controlling the pH value of the reaction solution at a certain value, controlling the reaction temperature, and dropwise adding sodium hypochlorite to perform an oxidation reaction;
(8) after the reaction, the layers were separated, and the organic layer was washed with an aqueous solution of sodium hydrogencarbonate, dried and concentrated to give N- (9-fluorenylmethoxycarbonyl) decylaminoacetaldehyde.
2. A synthesis method of telavancin intermediate as claimed in claim 1, wherein the organic base 1 is triethylamine, N-diisopropylamine or pyridine, preferably triethylamine.
3. A synthesis process of a telavancin intermediate as claimed in claim 1, wherein the organic base 2 is triethylamine, N-diisopropylamino or pyridine, preferably N, N-diisopropylamino.
4. The synthesis method of telavancin intermediate according to claim 1, wherein the ratio of aminoethanol to concentrate 1 in step 3) is 1-20, preferably 10/1, and the reaction temperature is 0-100 ℃, preferably 80-90 ℃.
5. A synthesis process of a telavancin intermediate as claimed in claim 1, wherein the organic base 3 is triethylamine, N-diisopropylamino or pyridine, preferably N, N-diisopropylamino.
6. The synthesis method of a telavancin intermediate as claimed in claim 1, wherein the reaction temperature in step (5) is not higher than 25 ℃, preferably-5-0 ℃.
7. The synthesis method of a telavancin intermediate as claimed in claim 1, wherein in the step (7), the reaction temperature is controlled at-10-25 ℃, preferably-5-0 ℃, and the reaction pH is controlled at 7-12, preferably 8-9.
8. The synthesis method of a telavancin intermediate as claimed in claim 1, wherein the concentration of sodium hypochlorite in step (7) is 10%, and the reaction detection is by TLC.
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| CN112592940A (en) * | 2020-12-16 | 2021-04-02 | 江西邦泰绿色生物合成生态产业园发展有限公司 | Biological enzyme synthesis method of N-fluorenyl methoxycarbonyl-decyl acetaldehyde |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003106399A2 (en) * | 2002-06-17 | 2003-12-24 | Theravance, Inc. | PROCESS FOR PREPARING N-PROTECTED β-AMINO ALDEHYDE COMPOUNDS |
| CN1610692A (en) * | 2001-08-24 | 2005-04-27 | 施万制药 | Process for preparing glycopeptide derivatives |
| CN101671242A (en) * | 2009-09-02 | 2010-03-17 | 烟台显华化工科技有限公司 | Method for synthesizing trans-4-(trans-4'-alkyl cyclohexyl) cyclohexanal |
| WO2011005959A1 (en) * | 2009-07-09 | 2011-01-13 | Plus Chemicals Sa | Process for the preparation of n-protected-decylaminoethanal |
| CN106631902A (en) * | 2016-09-23 | 2017-05-10 | 上海步越化工科技有限公司 | Method for preparing telavancin side chain 9H-fluoren-9-ylmethyl decyl(2-oxoethyl)carbamate |
| CN107325159A (en) * | 2016-04-29 | 2017-11-07 | 中国科学院上海药物研究所 | One class vancomycin derivatives, its preparation method, pharmaceutical composition and purposes |
| CN108821964A (en) * | 2018-04-13 | 2018-11-16 | 太仓运通新材料科技有限公司 | A kind of synthetic method of royal jelly acid |
-
2020
- 2020-01-20 CN CN202010063868.1A patent/CN111233713A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1610692A (en) * | 2001-08-24 | 2005-04-27 | 施万制药 | Process for preparing glycopeptide derivatives |
| WO2003106399A2 (en) * | 2002-06-17 | 2003-12-24 | Theravance, Inc. | PROCESS FOR PREPARING N-PROTECTED β-AMINO ALDEHYDE COMPOUNDS |
| WO2011005959A1 (en) * | 2009-07-09 | 2011-01-13 | Plus Chemicals Sa | Process for the preparation of n-protected-decylaminoethanal |
| CN101671242A (en) * | 2009-09-02 | 2010-03-17 | 烟台显华化工科技有限公司 | Method for synthesizing trans-4-(trans-4'-alkyl cyclohexyl) cyclohexanal |
| CN107325159A (en) * | 2016-04-29 | 2017-11-07 | 中国科学院上海药物研究所 | One class vancomycin derivatives, its preparation method, pharmaceutical composition and purposes |
| CN106631902A (en) * | 2016-09-23 | 2017-05-10 | 上海步越化工科技有限公司 | Method for preparing telavancin side chain 9H-fluoren-9-ylmethyl decyl(2-oxoethyl)carbamate |
| CN108821964A (en) * | 2018-04-13 | 2018-11-16 | 太仓运通新材料科技有限公司 | A kind of synthetic method of royal jelly acid |
Non-Patent Citations (2)
| Title |
|---|
| 刘泺等: "万古霉素衍生物-特拉万星的合成方法改进", 《有机化学》 * |
| 熊伦: "特拉万星的制备工艺研究及其类似物的合成与抗菌活性筛选", 《中国优秀硕士学位论文 医药卫生科技辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112592940A (en) * | 2020-12-16 | 2021-04-02 | 江西邦泰绿色生物合成生态产业园发展有限公司 | Biological enzyme synthesis method of N-fluorenyl methoxycarbonyl-decyl acetaldehyde |
| CN112592940B (en) * | 2020-12-16 | 2023-05-02 | 江西邦泰绿色生物合成生态产业园发展有限公司 | Biological enzyme synthesis method of N- (9-fluorenylmethoxycarbonyl) -decylaminoacetaldehyde |
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