Chemistry and Chemical Biology ETDs

Publication Date

11-20-1968

Abstract

The hydrolytic removal and subsequent reinsertion of carbon 2 of a series of 3-substituted-4-hydroxycoumarins has been accomplished. The removal of carbon 2 presents an effective synthetic route to o-hydroxyketones with complex side chains. o-Hydroxyketones when condensed with alkyl carbonates gave good yields of 4-hydroxycoumarins. When this was carried out with ethyl carbonate-carbonyl-14C a radio label was inserted in position 2. It was shown that this decarboxylation-carboxylation cycle did not involve racemization of an optically active α-carbon on a side chain in position 3. This method was used to prepare the enantiomers of Marcumar-2-14C(3-α-ethyl-benzyl-4-hydroxycoumarin). The enantiomers of warfarin-4-14C(3-α-acetonyl-benzyl-4-hydroxycoumarin) were prepared in a different manner. The urinary excretion rates of the separate isomers of Marcumar and warfarin in the rat were not sufficiently different to explain their differences in anticoagulant potencies. No activity was detected in expired carbon dioxide from Marcumar-2-14C.

Project Sponsors

The National Heart Institute, Public Health Service Grant No. R01-HE10527

Language

English

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Bruce David West

Second Committee Member

Raymond N. Castle

Third Committee Member

Roy Dudley Caton Jr.

Fourth Committee Member

Terence Joseph Scallen

Fifth Committee Member

Guido Herman Daub

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