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Synthesis of a library of tricyclic azepinoisoindolinones.

ABSTRACT: Hydrozirconation of 1-hexyne, the addition to in situ prepared N-acyliminium species, and ring-closing metathesis (RCM) were key steps in the preparation of a tricyclic isoindolinone scaffold. An unusual alkene isomerization process during the RCM was identified and studied in some detail. Chemical diversification for library synthesis was achieved by a subsequent alkene epoxidation and zinc-mediated aminolysis reaction. The resulting library products provided selective hits among a large number of high-throughput screens reported in PubChem, thus illustrating the utility of the novel scaffold.

SUBMITTER: Miller B

PROVIDER: S-EPMC3458725 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Synthesis of a library of tricyclic azepinoisoindolinones.

Miller Bettina B Mao Shuli S Rosenker Kara M George KM Pierce Joshua G JG Wipf Peter P

Beilstein journal of organic chemistry 20120713

Hydrozirconation of 1-hexyne, the addition to in situ prepared N-acyliminium species, and ring-closing metathesis (RCM) were key steps in the preparation of a tricyclic isoindolinone scaffold. An unusual alkene isomerization process during the RCM was identified and studied in some detail. Chemical diversification for library synthesis was achieved by a subsequent alkene epoxidation and zinc-mediated aminolysis reaction. The resulting library products provided selective hits among a large number ...[more]

PMID: 23019435

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