Stereochemistry of the biosynthesis of presqualene alcohol

G. Popják, Hark lim Ngan, William Agnew

Research output: Contribution to journalArticlepeer-review

Abstract

Current hypotheses of the biosynthesis of presqualene pyrophosphate were tested by the examination of presqualene alcohol biosynthesized from [1R,5R,9R-1,5,9-D3]farnesyl pyrophosphate and from [1-18O]farnesyl pyrophosphate. Nuclear magnetic resonance spectrometry showed that the octet of the two cyclopropylcarbinyl protons seen in the spectrum of protio-presqualene alcohol, centered at τ 6.35, was replaced by a broad doublet of one proton (τ, 6.23; J, 6.2 Hz), which became sharpened after deuterium decoupling and was reduced to a singlet after deuterium and proton decoupling. Also the doublet of a single olefinic proton adjacent to the cyclopropane ring, seen in the spectrum of protio-presqualene alcohol at τ 5.08 (J, 8.5 Hz), was reduced to a broad singlet. The presqualene alcohol biosynthesized from the [1-18O]farnesyl pyrophosphate contained the same isotopic concentration as its precursor. The observations, taken together with previous results, are interpreted to mean that the pyrophosphate-bearing group of one farnesyl pyrophosphate molecule appears without chhnge of configuration, and without previous cleavage of the CO bond of farnesyl pyrophosphate, in presqualene pyrophosphate and that the pro-R hydrogen atom at C-1 of the second farnesyl pyrophosphate molecule appears at C-3 of the cyclopropane ring anti to the vinylic substituent. The observations support the view that presqualene pyrophosphate is not an artifact, but a true intermediate in the biosynthesis of squalene.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalBioorganic Chemistry
Volume4
Issue number3
DOIs
StatePublished - Sep 1975
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

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