The Manufacture of a Homochiral 4-Silyloxycyclopentenone Intermediate for the Synthesis of Prostaglandin Analogues

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• 作者：Julian P. Henschke ; Yuanlian Liu ; Xiaohong Huang ; Yungfa Chen ; Dechao Meng ; Lizhen Xia ; Xiuqiong Wei ; Aiping Xie ; Danhong Li ; Qiang Huang ; Ting Sun ; Juan Wang ; Xuebin Gu ; Xinyan Huang ; Longhu Wang ; Jun Xiao ; Shenhai Qiu
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：December 21, 2012
• 年：2012
• 卷：16
• 期：12
• 页码：1905-1916
• 全文大小：378K
• 年卷期：v.16,no.12(December 21, 2012)
• ISSN：1520-586X

文摘

A process is described for the synthesis of kilogram quantities of homochiral 4-silyloxycyclopentenone (R)-1, a key intermediate useful for the synthesis of a plurality of prostaglandin analogue drugs. Cyclopentenone (R)-1 was synthesized in 14 isolated steps from furfural. Key steps in the synthesis include a Wittig reaction, Piancatelli rearrangement, and an enzymatic resolution featuring in situ recycling of the undesired enantiomer furnishing the desired homochiral alcohol in 鈮?9.5% ee. As a retort to the unsatisfactory coformation of about 8% at best of the trans-olefin in the Wittig reaction, a change to the order of several steps and the identification of a recrystallisable, amine salt derivative, 2, allowed the unwanted isomer to be controlled to as low as 0.2%.