Selective Substitution of 31/42–OH in Rapamycin Guided by an in Situ IR Technique

Molecules

Shuang Cao¹  Xinbo Zhou²  Yuanshuai Yang¹  Wu Zhong² 

[1] Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, China; E-Mails:;Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China; E-Mail:

关键词: rapamycin derivatives;    in situ IR;    selective substitution;    aqueous solubility;   

DOI  :  10.3390/molecules19067770

来源: mdpi

【 摘 要 】

An in situ IR technique was applied in the selective synthesis of the key intermediate for rapamycin derivatives, which made the reaction endpoint easily defined. This technology solved a bothersome problem in the preparation of rapamycin derivatives, and based on this technique, the 31-OH and 42-OH of rapamycin were chemically modified by a series of quaternary ammonium salts to generate 11 compounds. The solubility of all these compounds was remarkably improved (25,000 times higher than that of rapamycin) and their structures were confirmed by MS, IR, 1D and 2D NMR techniques.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.