61219-76-9

A synthetic route was developed for the preparation of deuterated mevalonolactones. Using low-cost deuterated reagents, this route allows for the independent introduction of deuterium labeling into any carbon position or into any combination of positions. Following this approach, the synthesis of [6,6,6-2H3]mevalonolactone, [4,4,6,6,6-2H 5]mevalonolact-one, [5,5-2H2]mevalonolactone, [5,5,6,6,6-2H5]mevalonolact-one, and [2,2,6,6,6- 2H5]mevalonolactone is described.

The biosynthesis of the saturated isoprenoid portion of membrane lipids of the halophilic archaea Natrinema pallidum was investigated. At first, a practical method for the synthesis of [3-(2H3)methyl]mevalonate was developed. Then, incorporation experiments of [3-(2H3)methyl]mevalonate into the lipid core indicated that the isoprenoid portion was derived from mevalonate. However, a [2-13C]acetate-incorporation experiment revealed a significant difference in the degree of 13C enrichment between the expected position from the mevalonate pathway, the CH2 groups (and at one terminal CH3 group) and the CH3 groups in the saturated isoprenoid chain. These results suggest that (1) the mevalonate pathway exists and is active, and (2) a part of acetoacetyl-CoA is not derived from an acetate in the biosynthesis of the isoprenoidal lipid-core of the archaebacterium.

Incubation of deuteriated precursors in cultures of Flavobacterium produced specifically deuteriated carotenoids. Analysis of these led to several conclusions: i) Lycopene is a direct precursor of β,β-carotene. ii) Its terminal Me groups retain their inte

Incorporation of 13C-labelled acetates and nethionine indicate that andibenin B (1) and andilesin A (5), C25 metabolites of Aspergillus variecolor, are biosynthesised via a mixed polyketide-terpenoid pathway, 18O-Labelling studies, and incorporation of aromatic precursors and mevalonic acids variously labelled with 13C, 2H and 18O provide evidence for the extensive oxidative and other modifications involved in the elaboration of the highly oxygenated polycyclic structures found in these metabolites. The biosynthetic interrelationships among these and other complex meroterpenoid metabolites are discussed.

Isotope administration experiments with Nicandra physaloides plants using 2H3>- and 14C3>-mevalonic acid, analysed by 2H NMR and by degradation, respectively, show that the aromatic ring-D of Nic-1 (2) is formed by ring-D expansion in a steroid precursor with oxidative inclusion of the C/D angular methyl.