SYNTHETIC EFFORTS DIRECTED TOWARDS THE TOTAL SYNTHESIS OF
THE POLYCYCLIC NATURAL PRODUCTS N-METHYLWELWISTATIN AND
COMMUNESIN B
Open Access
Author:
Crawley, Seth Lucas
Graduate Program:
Chemistry
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
June 01, 2006
Committee Members:
Raymond Lee Funk, Committee Chair/Co-Chair Ken S Feldman, Committee Member Steven M Weinreb, Committee Member Ming Tien, Committee Member
Keywords:
aza-ortho-xylylene N-methylwelwitindoline C isothiocyanate radical cyclization communesin intramolecular Diels-Alder cycloaddition
Abstract:
Part 1 discusses the investigation of a novel strategy for the total synthesis of N-methylwelwistatin. The key transformation involves sequential stereoselective 5-exo-trig, 7-endo-trig radical cyclizations to provide the tricyclic core ring system of N-methylwelwistatin. Strategies that were investigated for the completion of the total synthesis from the radical cyclization product include: 1) an intramolecular alkylation strategy; 2) an intramolecular [3+2] nitrone-olefin cycloaddition strategy; 3) an intramolecular radical cyclization strategy.
Part 2 reviews the synthetic efforts directed towards the total synthesis of communesin B. The core ring systems of both nomofungin and communesin B were synthesized via intramolecular cycloadditions of an indole tethered to an ortho-quinone methide and an aza-ortho-xylylene respectively. This work provided definitive proof that the structure of nomofungin was published erroneously. Attempts to complete the total synthesis using a benzazepine-based approach were unsuccessful, but have inspired a strategy employing a tryptamine-derived indole/aza-ortho xylylene intramolecular cycloaddition. This approach has led to the development of two novel means of generating aza-ortho-xylylenes: 1) the acid or base catalyzed ring opening of aziridines; 2) retrocycloaddition of acyl-N-acyl-3,1-benzoxazin-2-ones. Also, the acyl-N-acyl-3,1-bezoxazin-2-one route has indicated that the vicinal quaternary centers of communesin B could be installed via an alkylation strategy.
