- A facile and economic method for the synthesis of (S)-N-Boc-3′-hydroxyadamantylglycine
-
(S)-N-Boc-3′-hydroxyadamantylglycine (I) is an important intermediate of saxagliptin for type 2 diabetes mellitus (T2DM). It was prepared from 1-adamantanecarboxylic acid(1) via mild reaction with sulfuric acid/nitric acid, VHA reagent (SOCl2/DMF) and sodium diethyl malonate, then was treated with hydrolysis, decarboxylation, alkalization and oxidation to give 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (4), then through oximation, reduction and (Boc)2O protection to give the N-Boc-3′-hydroxyadamantylglycine(6), then was treated with quinidine to get (S)- N-Boc-3′-hydroxyadamantylglycine(I) and quinine to get (R)–N-Boc-3′-hydroxyadamantylglycine(II). Finally, Compound II was racemized by dicyclohexylcarbodiimide (DCC) and sodium?hydride (NaH) to afford compound 6. In this route, the overall yield of preparing compound I was about 35?% and the enantiomeric excess (ee) reach to 99?%. This route provided a novel idea for the preparation of (S)-N-Boc-3′-hydroxyadamantylglycine.
- Li, Jie,Jiang, Xue,Gan, Run,Zhang, Ming,Pan, Xinmei,Hu, Xiangnan
-
-
Read Online
- Synthetic method of saxagliptin intermediate (by machine translation)
-
(1) The compound 1 is reacted under the action of sodium ethoxide in a substitution reaction under the action of sodium ethoxide to form compound 2 by stirring and refluxing 2 under the action of sodium ethoxide to form compound 2; (8 hours) compound 3 is reacted 3 at room temperature under the alkaline condition by adding L - arginine to obtain a salvildagliptin intermediate, compound 3) and liquid bromine under the action of sodium ethoxide and then adding L-arginine under the action of sodium ethoxide under the action of sodium ethoxide and then 8 hours adding L-arginine 4 under the 4 action of 4 sodium ethoxide 12 hours. Raw materials and reagents are cheap and easily available, the reaction operation is simple, the reaction conditions are mild, the yield is high, the quality is good, the resolution end product can reach 99% ee values, and the requirements of drug intermediates are met. (by machine translation)
- -
-
Paragraph 0044-0046
(2020/11/23)
-
- Synthesis and biological evaluation of all eight stereoisomers of DPP-IV inhibitor saxagliptin
-
All eight stereoisomers of saxagliptin have been synthesized and evaluated for their inhibitory activity against DPP-IV. It was unambiguously confirmed that the configuration of saxagliptin was critical to potent inhibition of DPP-IV. Docking study was performed to elucidate the configuration-activity relationship of saxagliptin stereoisomers. Tyr662 and Tyr470 have been suggested as the key residues of DPP-IV interacting with the inhibitors. This work provides valuable information for further inhibitor design against DPP-IV.
- Dong, Jizhe,Gong, Yanchun,Liu, Jun,Chen, Xiangfeng,Wen, Xiaoan,Sun, Hongbin
-
p. 1383 - 1393
(2014/03/21)
-