Synthesis of tuckolide and an unexpected analogue of xestobergsterol A
Abstract
Tuckolide, a potent cholesterol biosynthesis inhibitor, was synthesized in fourteen steps in 5.6% overall yield. The key steps contain a Sharpless catalytic asymmetric dihydroxylation (AD) and a modified Corey-Nicolaou lactonization of the seco-acid. The selectivity of the AD step was found to be highly dependent on the nature of the protecting group adjacent to the diene. The synthesis establishes the absolute stereochemistry of tuckolide showing the C3 hydroxyl bearing carbon to have the S-configuration. Another project involved a model study directed toward the total synthesis of xestobergsterol A, a potent anti-histamine drug. An unexpected and interesting analogue was synthesized in eleven steps. The key features of this synthesis involved the novel higher order cyanocuprate reagent, $\rm(NCCH\sb2)\sb2CuCNLi\sb2,$ for an $\rm S\sb{N}2\sp\prime$ addition to an unsaturated epoxide and intramolecular aldol cyclization. Based on these results, the synthesis of natural xestobergsterol A is possible.
Degree
Ph.D.
Advisors
Andrus, Purdue University.
Subject Area
Organic chemistry
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