Date of Award

1981

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Abstract

The irregular terpene, 2,6,9,13-tetramethyl-6-vinyl-tetradeca-2,8,12-trien-7-one (18), and the terpenoid, 1-phenyl-2,6-dimethyl-2-vinyl-hept-5-en-1-one (19) were synthesized by the Continuous Flow Reformatsky method using geranoyl chloride and benzoyl chloride, respectively. Geranyl bromide was used to generate the required organo-zinc adduct. Citral and geranyl bromide produced 3,6,9,13-tetramethyl-9-vinyl-tetradeca-3,7,12-trien-6-ol (17) by this method. Attempts to isomerize 17 to 2,6,9,13-tetramethyl-6-vinyl-tetradeca-2,8,12-trien-7-ol failed. It is postulated that 17 is more stable due to steric compression around the quaternary carbon. Comparison of 18 and the terpene isolated from yeast enzyme preparations by Bell('135) showed them to be identical. Attempts to synthesize 2-hydroxygeranyl thiamine by the addition of thiamine to citral failed. Cinnamaldehyde also failed to react with thiamine to yield 2-hydroxycinnamyl thiamine. Thiamine and 3-methylbenzothiazolium hemisulfate both react with benzaldehyde to produce 2-benzoyl-3-(2-methyl-4-aminopyrimidin-5-yl) methyl-3a-methylperhydrofuro {2,3-d} thiazole (5) and 3-methylbenzothiazolinyl phenyl ketone (8), respectively. Since 8 is formed via a carbene, a similar proposal is made to account for the behavior of thiamine. Tritiated citronellal, prepared by the selective hydrogenation of the (alpha),(beta)-olefin of tritiated citral, was reacted with thiamine to produce labelled 2-(1-hydroxy-3,7-dimethyl-1-oct-6-enyl) thiamine chloride hydrochloride (('3)H-1). When ('3)H-1 was incubated with geraniol or farnesol 7% of the label was incorporated into 2,6,9,13-tetramethyl-6-vinyl-2,12-tetradecadien-7-one (18a) and 2,6,9,13,17-pentamethyl-9-vinyl-octadeca-2,11,16-trien-8-one (26), respectively. Labelling studies suggest that squalene synthetase is less specific for chain length of the terpene substrate at Site II, than at Site I. Also the thiamine thiazole mimics an isoprenoid moiety of farnesol and the cofactor is not involved in squalene synthesis as proposed by Woodward. The terpenoid, 2-(1-hydroxy-3,7-dimethyloct-6-enyl)-4-methyl-5-(2-hydroxyethyl) thiazole (2) was found to be inactive in yeast enzyme preparations.('). The formation of 2-alkyl derivatives of thiamine via the Hantzsch Thiazole Synthesis was investigated. Using model systems, S-phenacyl thiobenzanilide and S-(p-chlorophenacyl) thiononanilide were synthesized but failed to yield the desired thiazolium salts. Steric hindrance of the substituents was responsible for this failure. Thus, based on the isolation of 18 from the cell-free yeast enzyme preparation, it is suggested that while thiamine is not involved in tail-tail dimerization, the vitamin may play a role in the formation of artemisia ketone and bakuchiol.

Pages

195

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