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Highly Stereoselective Synthesis of Fused Cyclopropane-?-Lactams via Biocatalytic Iron-Catalyzed Intramolecular Cyclopropanation.

ABSTRACT: We report the development of an iron-based biocatalytic strategy for the asymmetric synthesis of fused cyclopropane-?-lactams, which are key structural motifs found in synthetic drugs and bioactive natural products. Using a combination of mutational landscape and iterative site-saturation mutagenesis, sperm whale myoglobin was evolved into a biocatalyst capable of promoting the cyclization of a diverse range of allyl diazoacetamide substrates into the corresponding bicyclic lactams in high yields and with high enantioselectivity (up to 99% ee). These biocatalytic transformations can be performed in whole cells and could be leveraged to enable the efficient (chemo)enzymatic construction of chiral cyclopropane-?-lactams as well as ?-cyclopropyl amines and cyclopropane-fused pyrrolidines, as valuable building blocks and synthons for medicinal chemistry and natural product synthesis.

SUBMITTER: Ren X

PROVIDER: S-EPMC7111458 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Highly Stereoselective Synthesis of Fused Cyclopropane-γ-Lactams via Biocatalytic Iron-Catalyzed Intramolecular Cyclopropanation.

Ren Xinkun X Chandgude Ajay L AL Fasan Rudi R

ACS catalysis 20200114 3

We report the development of an iron-based biocatalytic strategy for the asymmetric synthesis of fused cyclopropane-γ-lactams, which are key structural motifs found in synthetic drugs and bioactive natural products. Using a combination of mutational landscape and iterative site-saturation mutagenesis, sperm whale myoglobin was evolved into a biocatalyst capable of promoting the cyclization of a diverse range of allyl diazoacetamide substrates into the corresponding bicyclic lactams in high yield ...[more]

PMID: 32257580

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