Chemistry and Chemical Biology ETDs

Publication Date

4-23-1973

Abstract

Interest in the compounds described by this thesis was first aroused in the early 1930's when a research team began to investigate the mass poisonings of the population in Indonesia. The cause of the poisonings seemed to be the foodstuffs which the people made for themselves from the abundant coconut. Two products in particular, Bongkrek and Semaji, made from coconut presscakes and grated coconut, were apparently the source of the toxic substance. When made under improper conditions, the toxic principle developed in an otherwise harmless food product. A compound was finally isolated and established as the toxic principle by testing on animals. The structures of the toxic principle (named toxoflavin) and of another compound, xanthothricin, were shown to be identical. Both had antibiotic properties. Another antibiotic, fervenulin, was shown to be isomeric with toxoflavin. Synthesizing analogs of toxoflavin and fervenulin as possible antimetabolites grew from the above discoveries. By replacing the nitrogen atom at position 4 on the triazine ring with a carbon atom, it is possible that the antimetabolite characteristics might be retained and the toxicity to humans decreased. It is known that sometimes a small change in the structure of a compound can change some of its properties. The most important compound synthesized was 4-deazatoxoflavin, 1, 6-dimethy1-1, 5, 6, 7-tetrahydropyrimido [4, 5-c]-5,7-pyridazinedione (XV), by the cyclization of 6-(α-methylhydrazino)-3-methyluracil (XIII) with glyoxal. Two additional analogs of toxoflavin were synthesized by condensation reactions, namely: 1-benzyl-6-methy1-1, 5, 6, 7-tetrahydropyrimido­ [4, 5-c]-5, 7-pyridazinedione and 6-methy1-1-pheny1-1, 5, 6, 7-tetrahydropyrimido [4, 5-c]-5, 7-pyridazinedione. The principle intermediate from which the three important compounds were prepared was 6-chloro-3-methyluracil which was prepared from known methods. Another group of compounds, the pyrido[2, 3-d]pyrimidines also appeared of interest. Several intermediates were synthesized by replacing the chlorine atom of 6-chloro-3-methyluracil at position 6 with alkyl and aryl amines. Attempts to cyclize these aminopyrimidines to the requisite pyrido[2, 3-d]pyrimidines were unsuccessful.

Language

English

Document Type

Thesis

Degree Name

Chemistry

Level of Degree

Masters

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Raymond N. Castle

Second Committee Member

Lee Duane Hansen

Third Committee Member

Unknown

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