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Total Synthesis of Hinduchelins A-D, Stereochemical Revision of Hinduchelin A, and Biological Evaluation of Natural and Unnatural Analogues.

ABSTRACT: Here, we report the first total synthesis of hinduchelins A-D, a family of nontoxic catechol derivatives from Streptoalloteichus hindustanus, possessing a druglike chemotype and modest iron-chelating ability. A concise synthesis was developed employing methyl 5-methyloxazole-4-carboxylate as a single starting material to provide hinduchelins A-D (and unnatural analogues) in only four steps and 5-15% overall yields; moreover, the stereochemistry of hinduchelin A was reassigned from ( S) to ( R). Biological evaluation confirmed that natural and unnatural hinduchelins are weak iron chelators (siderophores).

SUBMITTER: Childress ES

PROVIDER: S-EPMC6863084 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Total Synthesis of Hinduchelins A-D, Stereochemical Revision of Hinduchelin A, and Biological Evaluation of Natural and Unnatural Analogues.

Childress Elizabeth S ES Garrison Aaron T AT Sheldon Jessica R JR Skaar Eric P EP Lindsley Craig W CW

The Journal of organic chemistry 20190508 10

Here, we report the first total synthesis of hinduchelins A-D, a family of nontoxic catechol derivatives from Streptoalloteichus hindustanus, possessing a druglike chemotype and modest iron-chelating ability. A concise synthesis was developed employing methyl 5-methyloxazole-4-carboxylate as a single starting material to provide hinduchelins A-D (and unnatural analogues) in only four steps and 5-15% overall yields; moreover, the stereochemistry of hinduchelin A was reassigned from ( S) to ( R). ...[more]

PMID: 31039303

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