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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

Stephanie W. Chun 
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
,
Alison R. H. Narayan  *
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
› InstitutsangabenThis 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).
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Publikationsverlauf

Received: 04. Februar 2019

Accepted after revision: 18. Februar 2019

Publikationsdatum:
19. März 2019 (online)

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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

Key words

biocatalysis - biosynthesis - α-oxoamine synthases - neurotoxins - α-amino ketones - pyridoxal-5′-phosphate
 

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