Application of Flow and Biocatalytic Transaminase Technology for the Synthesis of a 1-Oxa-8-azaspiro[4.5]decan-3-amine,Organic Process Research & Development

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Application of Flow and Biocatalytic Transaminase Technology for the Synthesis of a 1-Oxa-8-azaspiro[4.5]decan-3-amine
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2021-04-14 , DOI: 10.1021/acs.oprd.1c00075
Jeffrey T. Kohrt ₁ , Peter H. Dorff ₁ , Michael Burns ₂ , Chewah Lee ₂ , Steven V. O’Neil ₂ , Robert J. Maguire ₂ , Rajesh Kumar ₂ , Melissa Wagenaar ₂ , Loren Price ₁ , Manjinder S. Lall ₁

Affiliation

Spirocyclic ring systems are useful intermediates in the design and synthesis of medicinally active agents and commonly found as cores in natural products. Recently, syntheses of a key intermediate Boc-protected-1-oxa-8-azaspiro[4.5]decan-3-amine 1 were examined. While multigram quantities of the racemic material could be made from the reduction of an energic azide intermediate, larger scale reactions and a chiral synthesis required further investigations. Herein, we describe the use of a continuous three-step flow process to scale the formation and reduction of an azide intermediate, and the use of a transaminase to prepare the desired enantiomer in high yield and enantiomeric excess.

中文翻译：

流动和生物催化转氨酶技术在合成 1-Oxa-8-azaspiro[4.5]decan-3-amine 中的应用

螺环系统是设计和合成药物活性剂的有用中间体，通常作为天然产物的核心存在。最近，研究了关键中间体 Boc-protected-1-oxa-8-azaspiro[4.5]decan-3-amine 1的合成。虽然可以通过还原高能叠氮化物中间体来制备数克量的外消旋材料，但需要进一步研究更大规模的反应和手性合成。在这里，我们描述了使用连续三步流程来规模化叠氮化物中间体的形成和还原，以及使用转氨酶以高产率和对映体过量制备所需的对映体。

更新日期：2021-04-14

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