An Integrated Chemo-enzymatic Route for Preparation of 尾-Thymidine, a Key Intermediate in the Preparation of Antiretrovirals

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• 作者：Gregory E. R. Gordon ; Moira L. Bode ; Daniel F. Visser ; M. Jerry Lepuru ; Jacob G. Zeevaart ; Nasheen Ragubeer ; Molala Ratsaka ; David R. Walwyn ; Dean Brady
• 刊名：Organic Process Research & Development
• 出版年：2011
• 出版时间：January 21, 2011
• 年：2011
• 卷：15
• 期：1
• 页码：258-265
• 全文大小：279K
• 年卷期：v.15,no.1(January 21, 2011)
• ISSN：1520-586X

文摘

A chemo-enzymatic method for production of 尾-thymidine, an intermediate in the synthesis of antiretrovirals, is described. Guanosine and thymine were converted by means of enzymatic transglycosylation to yield 5-methyluridine (5-MU), which was reproducibly synthesised at a 10鈭?0-L scale in 85% yield at a final product concentration of 80 g路L^鈭?. A downstream processing (DSP) protocol was designed to remove reaction components interfering with the subsequent synthetic step. The crystallised 5-MU produced in the biocatalytic reaction was found to behave similarly to commercially available 5-MU, and the integration of the initial biocatalytic and subsequent three-step chemical process to 尾-thymidine was successfully demonstrated at bench scale.