Synlett 2019; 30(11): 1269-1274
DOI: 10.1055/s-0037-1611755
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© Georg Thieme Verlag Stuttgart · New York

Biocatalytic Synthesis of α-Amino Ketones

a  Department of Chemistry, , University of Michigan, 930 North University Ave, Ann Arbor, MI 48109-1055, USA
b  Life Sciences Institute, University of Michigan, 210 Washtenaw Ave, Ann Arbor, MI 48109-2216, USA   Email: arhardin@umich.edu
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a  Department of Chemistry, , University of Michigan, 930 North University Ave, Ann Arbor, MI 48109-1055, USA
b  Life Sciences Institute, University of Michigan, 210 Washtenaw Ave, Ann Arbor, MI 48109-2216, USA   Email: arhardin@umich.edu
› Author Affiliations
This research was supported by funds from the University of Michigan Life Sciences Institute and the National Institute of General Medical Sciences of the National Institutes of Health (R35 GM124880).
Further Information

Publication History

Received: 04 February 2019

Accepted after revision: 18 February 2019

Publication Date:
19 March 2019 (eFirst)

Abstract

Stereospecific generation of α-amino ketones from common α-amino acids is difficult to achieve, often employing superstoichiometric alkylating reagents and requiring multiple protecting group manipulations. In contrast, the α-oxoamine synthase protein family performs this transformation stereospecifically in a single step without the need for protecting groups. Herein, we detail the characterization of the 8-amino-7-oxononanoate synthase (AONS) domain of the four-domain polyketide-like synthase SxtA, which natively mediates the formation of the ethyl ketone derivative of arginine. The function of each of the four domains is elucidated, leading to a revised proposal for the initiation of saxitoxin biosynthesis, a potent neurotoxin. We also demonstrate the synthetic potential of SxtA AONS, which is applied to the synthesis of a panel of novel α-amino ketones.

1 Introduction

2 Native SxtA Module Activity

3 New Reactions with SxtA AONS

4 Conclusions and Outlook

 
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