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Preparative Asymmetric Synthesis of 4,4-Dimethoxytetrahydro-2H-pyran-3-ol with a Ketone Reductase and in Situ Cofactor Recycling using Glucose Dehydrogenase
Organic Process Research & Development ( IF 3.1 ) Pub Date : May 30, 2008 , DOI: 10.1021/op700255b
Birgit Kosjek 1 , Joseph Nti-Gyabaah 1 , Kathleen Telari 1 , Liam Dunne 1 , Jeffrey C. Moore 1
Affiliation  

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.

中文翻译:

酮还原酶的制备性不对称合成4,4-二甲氧基四氢-2H-吡喃-3-醇和葡萄糖脱氢酶的原位辅因子循环

4,4-二甲氧基四氢-2H-吡喃-3-酮的不对称酶酮还原提供了(R)-α-羟基缩酮,这是药物中间体的重要手性前体,具有高对映选择性(> 99%ee)。已经开发出一种经济的方法,包括使用葡​​萄糖脱氢酶进行原位NADPH辅因子再生,从而以高收率(96-98%)生产出所需的材料。在中试规模的工厂中采用了两种酶的方法,以生产80千克(R)-4,4-二甲氧基四氢-2H-吡喃-3-醇。发现扩大规模的关键因素是pH控制和搅拌速度。
更新日期:2017-01-31
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