Hanson 2 Mevalonic Acid

Full details have appeared of the incorporation of [2i - H,2- C,31 ]-, [2S- H,2- C,3i ]-, and [2- C,3/ ,5R- H]-mevalonic acids into kaurene (57), kaurenolides, and gibberellic acids. When [1- H2,2- C]- or [1- H2,1- C]-geraniol was used the radioactivity was retained in ent-kaurene (57), presumably with tritium at C-6. As expected, half of the tritium was lost with 7-hydroxy-ent-kaurenolide (60), 7,18-dihydroxy-cnt-kaurenolide (61), and gibberellic acid (63). However, Hanson has shown that gibbane aldehyde (62) retains all of the tritium, which means that in the ring contraction C-7 is oxidized and there is a hydrogen... 

A re-appraisal of the biosynthesis of the tricothecane-type sesquiterpenes is required in the light of labelling studies carried out by Hanson and co-workers. Incorporation of [2- C-4R,4- H]mevalonic acid into the culture medium of Tricothecium roseum and a Trichoderma species showed (a) that only two out of the three possible labels were incorporated in tricothecin [146, R = O, R = C(0)CH CH Me] and trichodermol (146, R = Hj, R = H) and (b) these tritium atoms were located at C-2 and C-10. Furthermore, on the basis of doublelabelling studies with [l.l- Hj, 2- C]- and [2- H,2- C]-farnesyl pyrophosphates, the authors concluded that cis,rrans-famesyl pyrophosphate is the preferred isomer for biosynthesis. 

Achilladelis and Hanson have studied the incorporation of [2- C,2- H2]-, [2- C,3J ,4R- H]-, and [2- C,5- H2]-mevalonic acid into rosane terpenoids (60). Their results, together with the non-incorporation of pimaradiene, excludes any diene intermediates between (59) and (60). Since labda-8(17),13-diene-15,19-diol... 

Interest in enzyme stereospecificity and the stereochemistry of prochiral centres, such as the methylene groups of mevalonic acid, has necessitated more precise definitions of the stereochemistry of the various molecules involved and of the enzymological consequences. The use of multiply labelled mevalonic acid in terpenoid and steroid biosynthesis has been reviewed by Hanson. The Proceedings of the 1970 Phytochemical Society symposium have been published. They include a general discussion of terpenoid pathways of biosynthesis by Clayton and specific chapters on monoterpenoids, diterpenoids, eedysones, carotenoids, isoprenoid quinones, and chromanols. Other reviews concerning biosynthesis have appeared on furanocoumarins, indole alkaloids, monoterpenoids, and diterpenoids. ... 

Hanson JR, Marten T, Siverns M (1974) Studies in Terpenoid Biosynthesis, Part XII. Carbon-13 Nuclear Magnetic Resonance Spectra of the Trichothecanes and the Biosynthesis of Trichothecolone from [2- C]-Mevalonic Acid. J Chem Soc, Perkin Trans 1 1033... 

The identity of C(8) of trichothecenes with C(2) of mevalonate was also proven directly, i.e., without the necessity of troublesome degradations and chemical conversions, by using [ Cjmevalonate (Hanson et ai, 1974). The only centers showing any enrichment in the C-NMR spectrum after the incorporation of [2- C]mevalonic acid into trichothecolone (25) were C(4), C(8), and C(14). That C(8)—and not C(10), as reported by Jones and Lowe (1960)—is derived from C(2) of mevalonate gives rise to the suggestion that the farnesyl pyrophosphate precursor of the trichothecenes is coiled as shown in structure 56, not as in structure 57 (Fig. 10) (Achilladelis et ai, 1970, 1972). 

---