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Formal synthesis of (-)-englerin A and cytotoxicity studies of truncated englerins.

ABSTRACT: An efficient formal synthesis of (-)-englerin A (1) is reported. The target molecule is a recently isolated guaiane sesquiterpene that possesses highly potent and selective activity against renal cancer cell-lines. Our enantioselective strategy involved the construction of the BC ring system of compound 1 through a Rh(II)-catalyzed [4+3] cycloaddition reaction followed by subsequent attachment of the A ring through an intramolecular aldol condensation reaction. As such, this strategy allows the synthesis of truncated englerins. Evaluation of these analogues with the A498 renal cancer cell-line suggested that the A ring of englerin is crucial to its antiproliferative activity. Moreover, evaluation of these analogues led to the identification of potent growth-inhibitors of CEM cells with GI(50) values in the range 1-3 ?M.

SUBMITTER: Xu J

PROVIDER: S-EPMC3338859 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Formal synthesis of (-)-englerin A and cytotoxicity studies of truncated englerins.

Xu Jing J Caro-Diaz Eduardo J E EJ Batova Ayse A Sullivan Steven D E SD Theodorakis Emmanuel A EA

Chemistry, an Asian journal 20120313 5

An efficient formal synthesis of (-)-englerin A (1) is reported. The target molecule is a recently isolated guaiane sesquiterpene that possesses highly potent and selective activity against renal cancer cell-lines. Our enantioselective strategy involved the construction of the BC ring system of compound 1 through a Rh(II)-catalyzed [4+3] cycloaddition reaction followed by subsequent attachment of the A ring through an intramolecular aldol condensation reaction. As such, this strategy allows the ...[more]

PMID: 22415793

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