Studies directed toward the total synthesis of cytochalasin C

Millagahamada Gedara Ranasinghe, Purdue University

Abstract

This thesis describes the results of the studies directed towards the total synthesis of cytochalasin C, a member of a group of fungal metabolities possessing a high level of biological activity. The synthetic strategy employs an intramolecular Diels-Alder reaction of a chiral Z-diene for construction of the tetrahydroisoindolone nucleus. Conjugate addition/alkylation reaction of a chiral vinyl sulfone with a $\beta$-keto ester dianion ultimately yields a tetracyclic precursor for an enolate-assisted intraannular fragmentation to construct the 11-membered macrocycle. A tricyclic precursor to the required pre-fragmentation substrate was prepared by an intramolecular Diels-Alder reaction of chiral Z-diene. Subsequent attempts at synthesis of this substrate by annulative methods were unsuccessful. Efficient methods for the preparation of symmetrical and unsymmetrical thiosulfonates, electrophilic and nucleophilic mecaptanylation with $\beta$-trimethylsilylethane thiol derived reagents, and a synthesis of exocyclic allylsilanes were discovered. The reaction of mercaptans with p-toluenesulfonyl bromide produced thiosulfonate esters. The reaction of 2-trimethylsilylethyl sulfides with dimethylthiomethylsulfornium fluoroborate produced disulfides which were subsequently transformed to mercaptans by reaction with tri-n-butylphosphine. Sulfenylation of an $\alpha$-sulfonyl anion with 2-trimethylsilylethyl thiosulfonate afforded an $\alpha$-sulfenylated sulfone which was oxidized to a bis-sulfone. This bis-sulfone was further functionalized and converted to exocyclic allylsilanes using the Rambergy-Backlund reaction. Chemodirected annulation of such allysilanes with fluoride or Lewis acids produced the trans- and cis-fused (4.3.0) bicyclononane ring systems.

Degree

Ph.D.

Advisors

Fuchs, Purdue University.

Subject Area

Organic chemistry

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