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Fluorous parallel synthesis of a piperazinedione-fused tricyclic compound library.

ABSTRACT: A fluorous-linker-assisted solution-phase protocol has been developed and applied to parallel synthesis of a piperazinedione-fused tricyclic compound library. The one-pot [3 + 2] cycloaddition of fluorous amino esters, aldehydes, and maleimides afforded bicyclic proline derivatives. The intermediates were subjected to N-acylation with chloroacetyl chloride, followed by displacement reactions with amines. Linker cleavage with concomitant lactamization yielded the final products. Microwave heating was employed to facilitate several reaction steps and fluorous solid phase extraction (F-SPE) was employed to purify the intermediates. During the method development, a small library containing sixteen analogs was prepared. The optimized conditions were applied to the synthesis of a production library containing ninety analogs.

SUBMITTER: Werner S

PROVIDER: S-EPMC2921976 | biostudies-literature | 2009 May-Jun

REPOSITORIES: biostudies-literature

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Fluorous parallel synthesis of a piperazinedione-fused tricyclic compound library.

Werner Stefan S Nielsen Simon D SD Wipf Peter P Turner David M DM Chambers Peter G PG Geib Steven J SJ Curran Dennis P DP Zhang Wei W

Journal of combinatorial chemistry 20090501 3

A fluorous-linker-assisted solution-phase protocol has been developed and applied to parallel synthesis of a piperazinedione-fused tricyclic compound library. The one-pot [3 + 2] cycloaddition of fluorous amino esters, aldehydes, and maleimides afforded bicyclic proline derivatives. The intermediates were subjected to N-acylation with chloroacetyl chloride, followed by displacement reactions with amines. Linker cleavage with concomitant lactamization yielded the final products. Microwave heating ...[more]

PMID: 19301852

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