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Irreversible endo-selective diels-alder reactions of substituted alkoxyfurans: a general synthesis of endo-cantharimides.

ABSTRACT: The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are shown to react with a variety of alternative dienophiles to generate 7-oxabicyclo[2.2.1]heptane derivatives under mild conditions. DFT calculations have been performed to rationalize the activation effect of the 3-alkoxy group on a furan Diels-Alder reaction.

SUBMITTER: Foster RW

PROVIDER: S-EPMC4406157 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Irreversible endo-selective diels-alder reactions of substituted alkoxyfurans: a general synthesis of endo-cantharimides.

Foster Robert W RW Benhamou Laure L Porter Michael J MJ Bučar Dejan-Krešimir DK Hailes Helen C HC Tame Christopher J CJ Sheppard Tom D TD

Chemistry (Weinheim an der Bergstrasse, Germany) 20150310 16

The [4+2] cycloaddition of 3-alkoxyfurans with N-substituted maleimides provides the first general route for preparing endo-cantharimides. Unlike the corresponding reaction with 3H furans, the reaction can tolerate a broad range of 2-substitued furans including alkyl, aromatic, and heteroaromatic groups. The cycloaddition products were converted into a range of cantharimide products with promising lead-like properties for medicinal chemistry programs. Furthermore, the electron-rich furans are sh ...[more]

PMID: 25756502

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