Chemoenzymatic Synthesis of the Four Diastereoisomers of 4-Hydroxypipecolic Acid from N-Acetyl-(R,S)-allylglycine: Chiral Scaffolds for Drug Discovery

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• 作者：Richard C. Lloyd ; Mark E. B. Smith ; Dean Brick ; Stephen J. C. Taylor ; David A. Chaplin ; and Raymond McCague
• 刊名：Organic Process Research & Development
• 出版年：2002
• 出版时间：November 2002
• 年：2002
• 卷：6
• 期：6
• 页码：762 - 766
• 全文大小：76K
• 年卷期：v.6,no.6(November 2002)
• ISSN：1520-586X

文摘

All four diastereoisomers of 4-hydroxypipecolic acid wereprepared in a form conveniently protected for drug discoveryapplications with the use of industrially scaleable methodology.Resolution of the racemic starting material using proprietaryacylases followed by an acyliminium ion cyclisation gavediastereomeric mixtures of 4-formyloxypipecolic acid, whichwere differentiated using an enzyme-catalysed hydrolysis. Theproducts were separated by partition, and by following asequence of straightforward chemical steps, the individualstereoisomers of the protected 4-hydroxypipecolates werecrystallized to optical purity in 100 g quantities.