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Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts.

ABSTRACT: An efficient, step-economical, and scalable synthesis of a diene-bearing AB spiroketal fragment of spongistatin 1, and a demonstration of its efficient coupling to an aldehyde derived from silylformylation of a homopropargyl alcohol to produce the entire complex C(13)-C(17) linker region are described. The scalability of the synthesis of the AB spiroketal fragment was demonstrated by the preparation of 34.5 grams by one chemist in ~60 workdays, and more than 40 grams overall. With this material in hand and having established a method for its efficient coupling to the CD fragment, we have set the stage for the rapid synthesis and evaluation of a series of analogs of the CD spiroketal.

SUBMITTER: Reznik SK

PROVIDER: S-EPMC4142563 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts.

Reznik Samuel K SK Leighton James L JL

Chemical science 20130401 4

An efficient, step-economical, and scalable synthesis of a diene-bearing AB spiroketal fragment of spongistatin 1, and a demonstration of its efficient coupling to an aldehyde derived from silylformylation of a homopropargyl alcohol to produce the entire complex C(13)-C(17) linker region are described. The scalability of the synthesis of the AB spiroketal fragment was demonstrated by the preparation of 34.5 grams by one chemist in ~60 workdays, and more than 40 grams overall. With this material ...[more]

PMID: 25165503

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