| 摘要 |
Disclosed is a process for the preparation of piperidinylsulfanylacetylmutilins of formula I wherein the carbon atom of the piperidine ring attached to the sulphur atom is either in the (S)-configuration or in the (R)-configuration and the 2-amino-3-methyl-butyryl group attached to the piperidine ring is either in the (S)-configuration or in the (R)-configuration, comprising the steps of: a) deprotecting an N-protected piperidinylsulfanylacetylmutilin of formula II and isolating a compound of formula III wherein the carbon atom Of the piperidine ring attached to the sulphur atom is either in the (S)-configuration or in the (R)-configuration, in free form or in the form of an acid addition salt, in crystalline form, b) acylating said compound of formula III with either (R)- or (S)-valine protected as an enamine and activated as a carbonic acid mixed anhydride to form a compound of formula VI wherein R1 and R2 are C1-4 alkyl, and R, is hydrogen or C1-4 alkyl, deprotecting the compound of formula IV and isolating the compound of formula I. Also disclosed is a compound of formula (IV); the acid salt of formula (III) in crystalline form; 14-O-[(N-3-methyI-2-(R)-amino-butyryl-piperidine-3(S)- yl)sulfanyl)acetyl]mutilin hydrochloride; and a pharmaceutical composition containing crystalline 14-O-[(N-3-methyI-2-(R)-amino-butyryl-piperidine-3(S)- yl)sulfanyl)acetyl]mutilin hydrochloride
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