Preparative Asymmetric Synthesis of 4,4-Dimethoxytetrahydro-2H-pyran-3-ol with a Ketone Reductase and in Situ Cofactor Recycling using Glucose Dehydrogenase

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• 作者：Birgit Kosjek ; Joseph Nti-Gyabaah ; Kathleen Telari ; Liam Dunne ; Jeffrey C. Moore
• 刊名：Organic Process Research & Development
• 出版年：2008
• 出版时间：July 2008
• 年：2008
• 卷：12
• 期：4
• 页码：584-588
• 全文大小：189K
• 年卷期：v.12,no.4(July 2008)
• ISSN：1520-586X

文摘

The asymmetric enzymatic ketone reduction of 4,4-dimethoxytetrahydro-2H-pyran-3-one provided the (R)-α-hydroxyketal, an important chiral precursor for a pharmaceutical intermediate, with high enantioselectivity (>99% ee). An economical process including in situ NADPH-cofactor regeneration using glucose dehydrogenase has been developed to produce the desired material in high yield (96–98%). The two-enzyme process was employed at pilot-plant scale to produce 80 kg of (R)-4,4-dimethoxytetrahydro-2H-pyran-3-ol. Critical factors for scale-up were found to be pH control and agitation speed.