Stereospecific Hydrogen Transfer from C-4 to C-6 during Enzymatic Transformation of Cholesterol into Cholestenone

概要

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In order to clarify the steric mechanism for biotransformation of ⊿^5-3β-hydroxysteroid into ⊿^4-3-ketosteroid the metabolic fate of hydrogen at C-4 during conversion of cholesterol into cholestenone by 3β-hydroxysteroid oxidase has been investigated. Of three substrates required for this purpose 4α-d_1-cholesterol was prepared through 4-d_1-cholest-4-en-3β-ol tert-butyldimethylsilyl ether as a key intermediate. The substrate was incubated with the enzyme, and the content and locality of deuterium in resulting cholestenone were determined by inspection of the mass, nuclear magnetic resonance, and infrared spectra. The transformation products formed from 4α-and 6-deuterated cholesterols retained the label almost intact, while that derived from 4β-d_1-cholesterol showed ca. 50% retention of the heavy isotope at 6β. Incubation studies using 6β-d_1-cholestenone as a substrate implied that a 50% loss of the label would be ascribable in part to the exchange with the incubation medium under the enzymatic control. These results led to a definite conclusion that 4β-hydrogen was transferred stereospecifically to the 6β-position during biotransformation of cholesterol into cholestenone.
公益社団法人日本薬学会の論文
1978-03-25