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Importance of a 4-Alkyl Substituent for Activity in the Englerin Series.

ABSTRACT: The ring closing metathesis/transannular etherification approach to the englerin nucleus was adapted to provide two key intermediates for analogue synthesis: the 4-desmethyl ?5,6 tricycle and the 4-oxo ?5,6 tricycle. The former was elaborated to 4-desmethyl englerin A and the latter served as a common precursor for englerin A, 4-ethyl englerin A, and 4-isopropyl englerin A. 4-Desmethyl englerin A was less active than the natural product by an order of magnitude, but the 4-ethyl and 4-isopropyl analogues were comparable in activity to englerin A. These results are consistent with the premise that the 4-alkyl group enforces the binding conformation of the cinnamoyl ester substituent. Furthermore, they suggest that 4-alkyl englerin structures may prove to be useful tool compounds.

SUBMITTER: Elliott DC

PROVIDER: S-EPMC5512125 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Importance of a 4-Alkyl Substituent for Activity in the Englerin Series.

Elliott Daniel C DC Beutler John A JA Parker Kathlyn A KA

ACS medicinal chemistry letters 20170606 7

The ring closing metathesis/transannular etherification approach to the englerin nucleus was adapted to provide two key intermediates for analogue synthesis: the 4-desmethyl Δ5,6 tricycle and the 4-oxo Δ5,6 tricycle. The former was elaborated to 4-desmethyl englerin A and the latter served as a common precursor for englerin A, 4-ethyl englerin A, and 4-isopropyl englerin A. 4-Desmethyl englerin A was less active than the natural product by an order of magnitude, but the 4-e ...[more]

PMID: 28740610

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