Transaminase Triggered Aza-Michael Approach for the Enantioselective Synthesis of Piperidine Scaffolds

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• 作者：James Ryan ; Mindaugas Šiaučiulis ; Andrew Gomm ; Beatriz Maciá ; Elaine O’Reilly ; Vittorio Caprio
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：December 14, 2016
• 年：2016
• 卷：138
• 期：49
• 页码：15798-15800
• 全文大小：260K
• ISSN：1520-5126

文摘

The expanding “toolbox” of biocatalysts opens new opportunities to redesign synthetic strategies to target molecules by incorporating a key enzymatic step into the synthesis. Herein, we describe a general biocatalytic approach for the enantioselective preparation of 2,6-disubstituted piperidines starting from easily accessible pro-chiral ketoenones. The strategy represents a new biocatalytic disconnection, which relies on an ω-TA-mediated aza-Michael reaction. Significantly, we show that the reversible enzymatic process can power the shuttling of amine functionality across a molecular framework, providing access to the desired aza-Michael products.