Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Chemistry

Supervisor

Dr. Michael Kerr

Abstract

Previous work done by the Kerr group has shown that tetrahydro-1,2-oxazines can be efficiently synthesized using a three component coupling reaction between a hydroxylamine, aldehyde and cyclopropane diester. This affords the desired heterocycle efficiently with a wide variety of substitution. When one esters bears an allyl group a Tsuji dehydrocarbonylation reaction may take place resulting in the formation of a 4,5-dihydro-1,2-oxazine. This motif contains a vinylogously acidic proton which is extremely labile and easily deprotonated. Under basic conditions this proton is removed and consequently the N-O bond is cleaved and subsequent condensation occurs forming a pyrrole. Using a sequence of chemical transformations specific pyrroles generated from the above methodology could be transformed into either BM 212 an anti-tuberculosis drug or Atorvastatin Calcium an anti-cholesterol drug. Each pharmaceutical will be derived using a three component coupling reaction and then conversion to a pyrrole followed by manipulations of the resulting functional groups.

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