Studies of terpenoid biosynthesis. Part 29. The cleavage of the sterol side chain in the biosynthesis of demethoxyviridin

Abstract

The structures of a group of C6 and C7 alcohols obtained from Nodulisporium hinnuleum have been elucidated. When biosynthesized from [2-14C]me~alonic acid they have been shown to have a specific activity consistent with a common origin with their co-metabolite, demethoxyviridin. The number of [2-2H2] mevalonoid hydrogen atoms which were incorporated suggests that they were formed initially at the aldehyde oxidation level.

The viridin family of steroidal antibiotics

“…The number and location of the hydrogen atoms originating from acetate and the 2-, 4-, and 5-positions of mevalonate were determined by a combination of 3H : 14C ratios in radioisotope feeding studies and 2H N M R studies. This work supported the intervention of a lanostane (35) rather than a cycloartenol (39) precursor, which would have been characteristic of plant steroid biosynthesis. The loss of a hydrogen atom from C-15 suggested that the removal of the C-14 methyl group followed a similar pathway to that found in other steroid biosyntheses.…”

“…The 13C NMR spectroscopic coupling pattern of wortmannin (34) biosynthesized from [ 1 ,2-13C2]acetate was also in accord with a triterpenoid biosynthetic pathway. 30 The incorporation of [3H]lanosterol (35) into viridin31 and w ~r t m a n n i n ~~ has been described. These studies also served to confirm the absolute stereochemistry of this series of compounds.…”

The use of stable isotopes in biosynthetic studies

“…spectra of the ( + )-methyl mandelate ester^. '^' If either (6R)-[6-2Ht]-or (6S)-[6-2H,]-~-glucose was incorporated into ribostamycin (265) by Streptomyces ribosidrJcus, the two hydrogen atoms at C-2 of the deoxystreptamine moiety were stereospecifically labelled. 287 In addition, the 6(pro-6R)hydrogen of the glucose is stereospecifically incorporated into the neosamine C unit, but the corresponding pro-S-hydrogen is lost.…”

Biosynthetic pathway for furanosteroid demethoxyviridin and identification of an unusual pregnane side-chain cleavage

“…To gain further insight into the biosynthesis of demethoxyviridin from lanosterol, Hanson et al identified a group of ergosterol side-chain-derived C6 and C7 alcohols sharing a common origin with demethoxyviridin. This suggested that the removal of the sterol side chain during demethoxyviridin biosynthesis occurs between C20 and C22, in a pathway analogous to the sterol side-chain cleavage during the biosynthesis of steroid hormones in mammalian cells 18 , 19 . Despite these advances, the genetic basis for the biosynthesis of furanosteroids has remained elusive.…”