Progress toward the total synthesis of the phomoidrides
The phomoidrides are a family of natural products isolated by Pfizer researchers in 1995 from the fermentation of an unidentified fungus found on twigs of a juniper tree in Dripping Springs, Texas. The phomoidride family of natural products display biological activity including inhibition of the enzyme squalene synthase and the enzyme Ras farnesyl transferase. The phomoidrides share many common structural motifs: a [4.3.1] bicyclic core containing a bridgehead olefin, a maleic anhydride, two different olefinic side chains, and an all-carbon quaternary center. The phomoidrides differ in the orientation of an epimerizable stereocenter and the open or closed form of a bridging -lactone ketal. The structural complexity of the phomoidrides has prompted many groups to target these molecules for total synthesis resulting in four completed total syntheses to date.
Over the last several years, research in the Wood group has evolved into a detailed retrosynthetic analysis directed toward the total synthesis of phomoidride D (1). The synthetic route targets a late-stage C-C bond fragmentation to install the bridgehead olefin. The carbon skeleton needed for the fragmentation is constructed using a novel SmI2 promoted radical anion cyclization that was developed in the Wood laboratory. Disconnection of the lactone 4 unveils a [2.2.2] bicyclic core that can be accessed via a phenolic oxidation intramolecular Diels-Alder reaction.
Name: Barry Twenter
Age: 26
Birthday: September 10, 1980
Graduate Level: 5th year
Undergrad: Illinois Institute of Technology
Degree: B.S. Chemistry
Graduate: Yale University
Degree: M.S. Chemistry
Hobbies: Baseball, poker, racquet ball, and looking good.
E-mail: barry.twenter@yale.edu
