An Efficient Large-Scale Synthesis of EDP-420, a First-in-Class Bridged Bicyclic Macrolide (BBM) Antibiotic Drug Candidate
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- 作者：Guoyou Xu ; Datong Tang ; Yonghua Gai ; Guoqiang Wang ; Heejin Kim ; Zhigang Chen ; Ly T. Phan ; Yat Sun Or ; Zhe Wang
- 刊名：Organic Process Research & Development
- 出版年：2010
- 出版时间：May 21, 2010
- 年：2010
- 卷：14
- 期：3
- 页码：504-510
- 全文大小：238K
- 年卷期：v.14,no.3(May 21, 2010)
- ISSN：1520-586X
文摘
A multistep, practical, and cost-effective synthesis of novel bridged bicyclic macrolide drug candidate EDP-420 (1) is described. Starting from inexpensive and commercially available erythromycin A 9-oxime, the current chemical process involves a series of transformations: triacetylation, Pd-catalyzed O,O-bis-allylation (bridge formation), acid-catalyzed sugar cleavage, oxime reduction, acetylation, Os-catalyzed bridge olefin oxidative cleavage, Corey−Kim oxidation, bridge oxime formation, deprotection, and final purification. Multikilogram quantities have been synthesized.