Synthesis of Trimegestone: The First Industrial Application of Bakers' Yeast Mediated Reduction of a Ketone
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- 作者：Vé ; ronique Crocq ; Christian Masson ; Jacques Winter ; Christian Richard ; Guy Lemaitre ; Jacques Lenay ; Michel Vivat ; Jean Buendia ; and Denis Prat
- 刊名：Organic Process Research & Development
- 出版年：1997
- 出版时间：January 1997
- 年：1997
- 卷：1
- 期：1
- 页码：2 - 13
- 全文大小：472K
- 年卷期：v.1,no.1(January 1997)
- ISSN：1520-586X
文摘
Trimegestone(17
-methyl-17
-(2(S)-hydroxy-1-oxopropyl)estra-4,9-dien-3-one) is a new progestomimetic moleculedeveloped by Roussel Uclaf for the treatment ofpostmenopausaldiseases. It is produced on an industrial scale from arelated3-ketal, 17-keto norsteroid intermediate in a nine-stepsequenceinvolving hydrocyanation of the 17-keto group, alkylationofthe protected cyanohydrin with ethyl magnesium bromide togive a 17-hydroxy 20-ketone, stereospecific17-methylationof the corresponding 17,20-enolate, and oxidation of the20,21-enolate with air and ketal deprotection to give3,20,21-triketone. The key step of the synthesis is the chemo-,regio-,and almost stereospecific bioreduction of this triketone tothedesired 21(S) alcohol, Trimegestone (de = 99%).This bioreduction is performed with bakers' yeast in water, thusshowingthe efficiency of this method at an industrial level.
-methyl-17-(2(S)-hydroxy-1-oxopropyl)estra-4,9-dien-3-one) is a new progestomimetic moleculedeveloped by Roussel Uclaf for the treatment ofpostmenopausaldiseases. It is produced on an industrial scale from arelated3-ketal, 17-keto norsteroid intermediate in a nine-stepsequenceinvolving hydrocyanation of the 17-keto group, alkylationofthe protected cyanohydrin with ethyl magnesium bromide togive a 17-hydroxy 20-ketone, stereospecific17-methylationof the corresponding 17,20-enolate, and oxidation of the20,21-enolate with air and ketal deprotection to give3,20,21-triketone. The key step of the synthesis is the chemo-,regio-,and almost stereospecific bioreduction of this triketone tothedesired 21(S) alcohol, Trimegestone (de = 99%).This bioreduction is performed with bakers' yeast in water, thusshowingthe efficiency of this method at an industrial level.