7OSN

IRED361 from Micromonospora sp. in complex with NADP+

7OSN の概要

• エントリーDOI: 10.2210/pdb7osn/pdb
• 分子名称: 6-phosphogluconate dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: amine, nadp, imine, oxidoreductase
• 由来する生物種: Micromonospora sp. Rc5
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 193848.74

構造登録者

Gilio, A.K.,Harawa, V.,Turner, N.,Grogan, G.J. (登録日: 2021-06-09, 公開日: 2022-06-22, 最終更新日: 2024-01-31)

主引用文献

Harawa, V.,Thorpe, T.W.,Marshall, J.R.,Sangster, J.J.,Gilio, A.K.,Pirvu, L.,Heath, R.S.,Angelastro, A.,Finnigan, J.D.,Charnock, S.J.,Nafie, J.W.,Grogan, G.,Whitehead, R.C.,Turner, N.J.
Synthesis of Stereoenriched Piperidines via Chemo-Enzymatic Dearomatization of Activated Pyridines.
J.Am.Chem.Soc., 144:21088-21095, 2022

PubMed Abstract: The development of efficient and sustainable methods for the synthesis of nitrogen heterocycles is an important goal for the chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds and their precursors. A potential biocatalytic approach to the synthesis of this privileged scaffold would be the asymmetric dearomatization of readily assembled activated pyridines. However, nature is yet to yield a suitable biocatalyst specifically for this reaction. Here, by combining chemical synthesis and biocatalysis, we present a general chemo-enzymatic approach for the asymmetric dearomatization of activated pyridines for the preparation of substituted piperidines with precise stereochemistry. The key step involves a stereoselective one-pot amine oxidase/ene imine reductase cascade to convert N-substituted tetrahydropyridines to stereo-defined 3- and 3,4-substituted piperidines. This chemo-enzymatic approach has proved useful for key transformations in the syntheses of antipsychotic drugs Preclamol and OSU-6162, as well as for the preparation of two important intermediates in synthetic routes of the ovarian cancer monotherapeutic Niraparib.

PubMed: 36350999
DOI: 10.1021/jacs.2c07143

実験手法

X-RAY DIFFRACTION (2.55 Å)