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Multistep Synthesis of 1,2,4-Oxadiazoles via DNA-Conjugated Aryl Nitrile Substrates.

ABSTRACT: A multistep protocol for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles on DNA-chemical conjugates has been developed. A set of six DNA-connected aryl nitriles were converted to corresponding amidoximes with hydroxylamine followed by the O-acylation with a series of aryl and aliphatic carboxylic acids. After cyclodehydration of the O-acyl amidoximes by heating at 90 °C in pH 9.5 borate buffer for 2 h, the desired oxadiazole products were observed in 51-92% conversion with the cleavage of O-acylamidoximes as the major side-product. The reported protocol paves the way for the synthesis of oxadiazole core-focused DNA-encoded chemical libraries.

SUBMITTER: Du HC

PROVIDER: S-EPMC6786255 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Multistep Synthesis of 1,2,4-Oxadiazoles via DNA-Conjugated Aryl Nitrile Substrates.

Du Huang-Chi HC Bangs Madison C MC Simmons Nicholas N Matzuk Martin M MM

Bioconjugate chemistry 20190410 5

A multistep protocol for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles on DNA-chemical conjugates has been developed. A set of six DNA-connected aryl nitriles were converted to corresponding amidoximes with hydroxylamine followed by the O-acylation with a series of aryl and aliphatic carboxylic acids. After cyclodehydration of the O-acyl amidoximes by heating at 90 °C in pH 9.5 borate buffer for 2 h, the desired oxadiazole products were observed in 51-92% conversion with the cleavage of O ...[more]

PMID: 30964278

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