title: 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.
authors.affiliation: Department of Chemistry, Columbia University, 3000 Broadway, New York, New York, 10027, USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Reznik
authors.affiliation: Department of Chemistry, Columbia University, 3000 Broadway, New York, New York, 10027, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Leighton