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Myoglobin-Catalyzed C-H Functionalization of Unprotected Indoles.

ABSTRACT: Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal-catalyzed carbene transfer has provided an attractive route to afford C3-functionalized indoles, these protocols are viable only in the presence of N-protected indoles, owing to competition from the more facile N-H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C-H functionalization of unprotected indoles is reported. Engineered variants of myoglobin provide efficient biocatalysts for this reaction, which has no precedents in the biological world, enabling the transformation of a broad range of indoles in the presence of ethyl α-diazoacetate to give the corresponding C3-functionalized derivatives in high conversion yields and excellent chemoselectivity. This strategy could be exploited to develop a concise chemoenzymatic route to afford the nonsteroidal anti-inflammatory drug indomethacin.

SUBMITTER: Vargas DA

PROVIDER: S-EPMC6376986 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Myoglobin-Catalyzed C-H Functionalization of Unprotected Indoles.

Vargas David A DA Tinoco Antonio A Tyagi Vikas V Fasan Rudi R

Angewandte Chemie (International ed. in English) 20180706 31

Functionalized indoles are recurrent motifs in bioactive natural products and pharmaceuticals. While transition metal-catalyzed carbene transfer has provided an attractive route to afford C3-functionalized indoles, these protocols are viable only in the presence of N-protected indoles, owing to competition from the more facile N-H insertion reaction. Herein, a biocatalytic strategy for enabling the direct C-H functionalization of unprotected indoles is reported. Engineered variants of myoglobin ...[more]

PMID: 29905974

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