R. B. Clayton

Some aspects of substrate specificity in biological demethylation at C4 of steroids

Abstract In order to ascertain some of the structural requirements for substrate activity in the oxidative demethylation at C4 of steroids by rat liver enzymes, several steroids have been synthesized, labeled with tritium, and incubated with rat liver enzyme preparations. These include 4α-formyl-4β-methylcholestan-3β-ol ( 4 ), 4-methylcholest-3-ene ( 14 ), 3β,4β-epoxy-4α-methylcholestane ( 20 ), 3α,4α-epoxy-4β-methylcholestane ( 18 ), 4α-ethyl-4β-methylcholestan-3β-ol ( 21 ), and 4β-ethyl-4α-methylcholestan-3β-ol ( 22 ). Enzymic incubation demethylates 4 with an efficiency consistent with its being an intermediate in the biological demethylation of 4,4-dimethyl sterols, but all of the other substrates are recovered unchanged.

The role of substrate structure in the initiation of enzymic cyclization of squalene 2,3-oxide. Stereochemistry of homosterol formation from 1-methylsqualene 2,3-oxide

Squalene 2,3-oxide lanosterol cyclase selectively converts the 1′-cis-methyl isomer as a component in a mixture of cis- and trans-1-methylsqualene 2,3-oxides into 4α-ethyl-4β,14α-dimethylcholesta-8,24-dien-3β-ol.

Stereochemistry of sterol biosynthesis: interrelationship of the terminal methyl groups in squalene, the C-1,1′ methyls in squalene 2,3-oxide, and the C-30,31 methyls in lanosterol

The trans-terminal methyls of squalene derive from C-2 of mevalonic acid, and the conversion of squalene in turn into squalene 2,3-oxide and lanosterol occurs without interchange of isopropylidene methyls, so that C-2 of mevalonic acid provides the 4α-methyl group of lanosterol.