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Synlett 2017; 28(10): 1151-1159
DOI: 10.1055/s-0036-1588768
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© Georg Thieme Verlag Stuttgart · New York

Chemoenzymatic Synthesis of Ubiquitous Biological Redox Cofactors

Priyanka Singh ◊
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA   Email: amnon-kohen@uiowa.edu
,
Qi Guo ◊
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA   Email: amnon-kohen@uiowa.edu
,
Amnon Kohen*
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA   Email: amnon-kohen@uiowa.edu
› Author Affiliations
Further Information

Publication History

Received: 12 December 2016

Accepted after revision: 08 March 2017

Publication Date:
10 April 2017 (online)

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◊ These authors contributed equally to this work.

Abstract

Redox cofactors are utilized by a myriad of proteins, ranging from metabolic enzymes to those performing post-translational modifications. Labeled redox cofactors have served as a vital tool for a broad range of studies. This account describes chemoenzymatic syntheses of the isotopically labeled, biologically important redox cofactors: nicotinamide adenine dinucleotide, methylene tetrahydrofolate, and flavin nucleotides. An overview of the general strategy is presented. These examples demonstrate the utility of enzymatic synthesis.

1 Introduction

2 Nicotinamide Cofactors

2.1 Synthesis of Remote-Labeled 14C-NADPH

2.1.1 Synthesis of [Ad-14C]NADPH

2.1.2 Synthesis of [Carbonyl-14C]NADPH

2.2 Synthesis of S- and R-[4-3H]NADPH

2.2.1 One-Step S- and Three-Step R-[4-3H]NADPH Synthesis

2.2.2 One-Pot, One-Step R-[4-3H]NADPH Synthesis

2.3 Synthesis of S- and R-[Ad-14C, 4-2H]NADPH

2.3.1 One-Step S-, Three-Step R-[Ad-14C, 4-2H]NADPH Synthesis

2.3.2 One-Pot, One-Step R-[Ad-14C, 4-2H]NADPH Synthesis

3 Methylene Tetrahydrofolate

4 Flavin Nucleotides

5 Conclusions and Outlook

Key words

chemoenzymatic synthesis - isotopic labeling - nicotinamide - flavin - methylene tetrahydrofolate