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

被引：24

作者：

Henschke, Julian P. ^{[1
]}

Liu, Yuanlian ^{[2
]}

Huang, Xiaohong ^{[2
]}

Chen, Yungfa ^{[1
]}

Meng, Dechao ^{[2
]}

Xia, Lizhen ^{[2
]}

Wei, Xiuqiong ^{[2
]}

Xie, Aiping ^{[2
]}

Li, Danhong ^{[2
]}

Huang, Qiang ^{[2
]}

Sun, Ting ^{[2
]}

Wang, Juan ^{[2
]}

Gu, Xuebin ^{[2
]}

Huang, Xinyan ^{[2
]}

Wang, Longhu ^{[1
]}

Xiao, Jun ^{[2
]}

Qiu, Shenhai ^{[2
]}

机构：

[1] ScinoPharm Taiwan Ltd, Tainan 74144, Taiwan

[2] ScinoPharm Changshu Pharmaceut Ltd, Changshu 215513, Jiangsu, Peoples R China

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2012年 / 16卷 / 12期

关键词：

ASYMMETRIC DIHYDROXYLATION; ANTIGLAUCOMA; CYCLOPENTENONES; BIMATOPROST; ENISOPROST; POTENT; FURANS;

D O I：

10.1021/op300188x

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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 >= 99.5% 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%.

引用

页码：1905 / 1916

页数：12

共 41 条

[1] Sharpless asymmetric dihydroxylation on an industrial scale [J].