The mechanism of the alkylation step in ergosterol biosynthesis

Biosynthesis of 24-ethylcholesta-5,22,25-trien-3β-ol, a new sterol from Clerodendrum campbellii

“…This therefore eliminates the possible operation of pathways (a), (b) and (c) in the biosynthesis of compound (V) and is in accordance with the operation of a pathway such as (d). A 3H/14C ratio 6:6 for 25-methylenecycloartanol is in agreement with previous reports (Akhtar et al 1966;Raab et al 1968;Goad & Goodwin, 1969;Rees et at. 1968) in which the tritium originally present at C-24 has been relocated at C-25.…”

“…When [2-14C,(4R)-4-3HJ]mevalonate is used as substrate cycloartenol, the postulated phytosterol precursor, will be labelled with 3H at the 3ax-, 50c-, 8fi-, 17a-, 20-and 24-positions and with 14C at C-1, C-7, C-15, C-22, C-26 or -27 and C-30 (Rees, Goad & Goodwin, 1968). It has been demonstrated (Castle, Blondin & Nes, 1963;Bader, Guglielmetti & Arigoni, 1964;Villanueva, Barbier & Lederer, 1964) that the 24-ethyl group present in various phytosterols arises by two successive transmethylations from methionine, and that during the first alkylation at C-24 to give a 24-methylene compound there is a hydrogen migration from C-24 to C-25 (Scheme 1, I-III) (Akhtar, Hunt & Parvez, 1966;Raab, de Souza & Nes, 1968;Goad & Goodwin, 1969). Alkylation of structure (III) leads to the carbonium ion (IV), which can conceivably be stabilized in a number of ways to give the A25-sterol (Smith, Goad, Goodwin & Lederer, 1967).…”

The introduction of the C-22–C-23 ethylenic linkage in ergosterol biosynthesis

“…On the basis of some past work that was misinterpreted in the original paper (Stone & Hemming, 1965), two recent reports (Stone & Hemming, 1967;Frantz & Schroepfer, 1967) have speculated on the mechanism of the alkylation step in ergosterol biosynthesis. The same mechanism, however, had been unambiguously established by us (Akhtar, Parvez & Hunt, 1966a;Akhtar, Hunt & Parvez, 1966b) before these speculations. It was proved that the C-alkylation step in ergosterol biosynthesis proceeds through the intermediacy of a 24-methylene compound (Akhtar et al 1966a; Barton, Harrison & Moss, 1966) by the mechanism shown in the sequence (I) -*(IV) (Scheme 1).…”

The stereochemistry of the hydrogen elimination in the biological conversion of cholest-7-en-3-β-ol into cholesterol

“…This mechanism involves a proton addition at C-8 to yield an electron-deficient species at C-7, which may then furnish cholesterol by an intramolecular transfer of a hydride ion from C-6 to C-7 followed by proton elimination from C-5 (Scheme 4). A mechanism of this type has recently been considered in the biosynthesis of methyl sterols (Akhtar, Hunt & Parvez, 1966). This mechanism would require the retention of both 6-hydrogen atoms in cholesterol.…”