File(s) under embargo

Reason: Pending Publication

12

day(s)

until file(s) become available

Total Synthesis of Decytospolides A and B and Progress Towards the Total Synthesis of Carambolaflavone A

thesis
posted on 14.12.2020, 22:30 by Hannah M SimpsonHannah M Simpson
Decytospolides A and B are natural products isolated from Cytospora sp. No ZW02 that show mild anticancer properties. The interest in synthesizing these compound lies not in their activities, but rather the simplicity of the structure which could easily be modified to provide more potent derivatives. Previous syntheses of these compounds relied on transition metals to install the tetrahydropyran core or extensive use of protecting groups. Our first generation synthesis made use of the Achmatowicz rearrangement to synthesize the tetrahydropyran moiety. Based on this, a concise, protecting group free synthesis has been accomplished utilizing the Achmatowicz rearrangement of an optically active furanyl alcohol followed by diastereoselective Kishi reduction of the resulting dihydropyranone hemiacetal.

Carambolaflavone A is a natural product isolated from A. carambola with antidiabetic properties. Notably, these compound promote both insulin secretion and glucose uptake by muscle cells in hyperglycemic rats. A previous synthesis has been reported by Wang and coworkers, however this synthesis does not offer much potential for the formation of derivatives and relies on a C-glycosylation that requires heating for regio- and diastereoselectivity. Progress towards a concise synthesis has been made featuring a Lewis acid promoted highly diastereoselective substrate controlled C-glycosylation that does not require heating and a one pot oxidation of chroman to chromone utilizing DDQ. Further research is underway to complete the synthesis of this molecule by an oxidative addition to the chromone and subsequent removal of protecting groups.

History

Degree Type

Doctor of Philosophy

Department

Chemistry

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Arun K. Ghosh

Additional Committee Member 2

Paul G. Wenthold

Additional Committee Member 3

Christina W. Li

Additional Committee Member 4

Abram Axelrod