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Journal of the Korean Chemical Society (JKCS)

ISSN 1017-2548(Print)
ISSN 2234-8530(Online)
Volume 59, Number 6
JKCSEZ 59(6)
December 20, 2015 

 
Title
Preparation of (S)-(+)-Pranidipine by Optical Resolution

광학 분할에 의한 (S)-(+)-Pranidipine의 제조방법
Author
Du Jong Baek*, Ji Hye Yoon, Moon Sik Kim

백두종*, 윤지혜, 김문식
Keywords
(S)-(+)-pranidipine, 칼슘채널 차단제, 항고혈압제, 광학 분할, 거울상 초과량 , (S)-(+)-Pranidipine, Calcium channel blocker, Antihypertensive drug, Optical resolution, Enantiomeric excess
Abstract
본 연구에서는 칼슘채널 차단제로서 항고혈압 작용을 가진 (S)-(+)-pranidipine의 광학 분할에 의한 효과적인 제조방 법을 제시하였다. (±)-Pranidipine을 가수분해시켜 얻은 monocarboxylic acid 5의 라세미 혼합물에 광학 활성이 있는 quinidine 을 첨가하여 염을 형성한 다음 불용성 부분입체이성질체 염을 여과하고 염기와 산으로 처리하여 (R)-(-)-carboxylic acid 7을 분리하였고 이 carboxylic acid를 cinnamyl alcohol과의 에스터화 반응에 의해 (S)-(+)-pranidipine을 합성하였다. 이 화합물의 거 울상 초과량(enantiomeric excess, ee)을 카이랄 HPLC로 분석한 결과 100% ee 값이 얻어졌고, 합성 과정에서 강염기 사용과 무수 조건 및 초저온 조건을 배제하였는바 이는 산업상 매우 유용한 개량방법이라 하겠다.

In this study, the effective preparation method of (S)-(+)-pranidipine, the active component of antihypertensive drug as a calcium channel blocker, was developed using optical resolution. The racemic monocarboxylic acid 5 obtained by the hydrolysis of (±)-pranidipine was mixed with optically active quinidine to form salts, and the insoluble diastereomeric salt was collected and successive treatment with base and acid furnished (R)-(-)-carboxylic acid 7. (S)-(+)-Pranidipine was prepared by esterification of this acid with cinnamyl alcohol, and the analysis by chiral HPLC showed 100% enantiomeric excess (ee). This process would be industrially very useful to prepare chiral (S)-(+)-pranidipine, since the use of strong base and anhydrous solvents, and ultra-low temperature condition were excluded in this process.

Page
488 - 492
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