Novel Syntheses of Medicinal Drugs via Organometallic Reagents

University Of Texas-Pan American, Edinburg TX

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The primary objectives of the present proposal are to develop new synthetic methodologies via organoborane reagents and to utilize them in the synthesis of useful medicinal drugs. The highly regio- and stereoselective synthesis of gem-dimetallic compounds containing boron-tin and boron-silicon and their synthetic versatility to prepare a retinoid, tamarotene and drugs such as phenoxan and 3-methyl-4-phenyl-3-butenoic acid are presented. The differences in the reactivity between carbon-silicon bond and carbon-tin bond are also explored. Phenoxan was discovered to have an anti-HIV activity and 3-methyl-4-phenyl-3-butenoic acid is an antihypercholesterolemic drug. The synthesis of drugs such as capillin, and capillen, which are antifungal and antibacterial agents respectively, are proposed based on thexyldialkynylborane intermediate. The preparation of tolboxane, a tranquilizer, 2-phenylphenol, an antiseptic drug, and benzomopine, antihypertensive drug, are also proposed based on palladium catalyzed cross-coupling reactions. A promising synthetic route to prepare tamoxifen which is used in the breast cancer treatment via the stepwise palladium catalyzed cross-coupling reaction of a stereodefined vic-dimetallic compound containing boron and tin is presented. These synthetic sequences will also be extended to synthesize oeplexyl and oestrobin which are synthetic estrogens. Finally, a novel synthetic approach to prepare optically active ibuprofen and naproxen which are analgesic drugs is explored based on organoboranes. The overall objective of the proposed studies is to introduce minority undergraduate students in biomedical research involving organoborane chemistry.