Synthesis of trimegestone: The first industrial application of bakers' yeast mediated reduction of a ketone

被引：28

作者：

Crocq, V ^{[1
]}

Masson, C ^{[1
]}

Winter, J ^{[1
]}

Richard, C ^{[1
]}

Lemaitre, Q ^{[1
]}

Lenay, J ^{[1
]}

Vivat, M ^{[1
]}

Buendia, J ^{[1
]}

Prat, D ^{[1
]}

机构：

[1] Roussel UCLAF, Direct Rech Procedes Chim, F-93235 Romainville, France

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 1997年 / 1卷 / 01期

关键词：

D O I：

10.1021/op960004h

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Trimegestone (17 alpha-methyl-17 beta-(2(S)-hydroxy-1-oxopropyl)-estra-4,9-dien-3-one) is anew progestomimetic molecule developed by Roussel Uclaf for the treatment of postmenopausal diseases. It is produced on an industrial scale from a related 3-ketal, 17-keto norsteroid intermediate in a nine-step sequence Involving hydrocyanation of the 17-keto group, alkylation of the protected cyanohydrin with ethyl magnesium bromide to give a 17 alpha-hydroxy 20-ketone, stereospecific 17 alpha-methylation of the corresponding 17,20-enolate, and oxidation of the 20,21-enolate with air and ketal deprotection to give 3,20,21-triketone. The key step of the synthesis is the chemo-, regio-, and almost stereospecific bioreduction of this triketone to the desired 21(S) alcohol, Trimegestone (de = 99%). This bioreduction is performed with bakers' yeast in water, thus showing the efficiency of this method at an industrial level.

引用

页码：2 / 13

页数：12

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