Homomevalonic acid

At the present time the candidacy of homomevalonic acid as a precursor of JH I and JH II is still attractive even though this compound has never been isolated from any living system. 

Similarly, the experiments of Matolcsy et al. (1974a 1974b 1975), in which several metabolite analogues of mevalonic acid and homomevalonic acid have been tested for anti-juvenile action, were unsuccessful. Support for the rationale that these metabolite analogues would block the formation of juvenile hormone at the mevalonate level was provided by the successful inhibition of cholesterol biosynthesis by mevalonate analogues in humans. Yet, a fluorinated mevalonate analogue, 4-fluoromethyl-4-hydroxy-tetrahydro-2H-pyran-2-one (FMev, 72) was found to act as a potent inhibitor of JH biosynthesis by Quistad and co-workers... 

JH III (34), the third juvenile hormone, is of course produced from three molecules of mevalonic acid (35) in the normal way]. Recent studies have provided support for these schemes by demonstrating that 3-hydroxy-3-ethyl-glutaric [c/. (26)], homomevalonic (27), and mevalonic acid (35) can be synthesized by crude enzymes isolated from the corpora allata of Manduca sexta ... 

Proceedings of the National Academy of Sciences, USA, 1973,70, 2921), have shown that homomevalonate starts with a propionic acid molecule as shown in Figure 6.23. In some insects it is known that the propionate is derived from isoleucine or valine only. The intermediate 3-methylenepentyl pyrophosphate in Figure 6.23 can be isomerized to two other structures. From these are obtained by reaction with IPP or DMAPP, compounds with either a terminal ethyl branch, an internal ethyl branch or two vicinal methyl branches (Figure 6.23). All three possibilities are found among insect compounds but the one on the left seems more common. 

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