Mevalonic lactone

Ketene dimer (28), made from [ " Cl-labelled acetic acid, has been used to make doubly labelled mevalonic lactone (29) for studies on the biosynthesis of terpenes. Note... 

Lactone, C(H.0O3, mevalolactone, mevalonic lactone,, i. hydroxv-,1 -methyl-0-nitcrolaclone. Hygroscopic crystals, mp 28°. 

Note MLMA-MAdMA=mevalonic lactone methacrylate (MLMA), 2-methyl-2-adamantane methacrylate (2-MAdMA) copolymer, (51 49). 

Baird et al. (I96I) have confirmed the terpenic origin of this antibiotic by adding mevalonic lactone-2-C to the medium and observing incorporation. It appears that cephalosporin Pi (I) is biosynthesized from II, a cationic precursor of fusidic acid, by the appropriate transformations. 

However, a full terpene origin for (II) was confirmed by incorporation of [2- C]-mevalonic lactone, which took place only in the nucleus ozonolysis gave acetone with one-third of the label of (II) indicating the presence of three isoprene units. 

When racemic mevalonic acid as the corresponding lactone and labeled at C-2 with is fed to the Chilean shmb SJ tanthus acutusM.ejen. labeled p-skytanthine [24282-31-3] (115) is obtained. Skjtanthus alkaloids are reputed to be tremorgenic (85). 

There is some interesting new methodology that has been worked out in the course of these studies 73>76>. in general, stereospecificity relations of this sort are examined with the help of other enzyme reactions of known stereospecificity. When mevalonic acid (lactone form, 8 is fed to Claviceps, the 5-Hs atom is incorporated into the ergot alkaloids agroclavin 9a and elymoclavin 9b, whereas the 5Hr, atom is lost. 

The therapeutic class that uniquely exemplifies lactone prodrugs are the statins, i.e., the cholesterol-lowering agents that act by inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34). This microsomal enzyme catalyzes conversion of HMG-CoA to mevalonate, an important rate-limiting step in cholesterol biosynthesis. Cholesterol synthesis occurs mainly... 

Mevalonic acid lactone. Mevalonic acid 5-phosphate, Mevalonic acid 5-pyrophosphate... 

It is difficult to identify the lipid moiety as a polyprenol, because of the small amounts present in tissues. Nevertheless, some information can be obtained by using glycosylated lipids labelled in the sugar moiety. The first indication of the presence of polyprenyl glycosyl phosphates comes from study of the properties just mentioned, namely, lability to mild acid, stability to mild alkali, and acidic properties. Information on the polyprenyl nature of the lipid may be obtained by labelling the lipid with radioactive 2,4-dideoxyO-C-methyl-D-g/ycero-pentono-l.S-lactone (mevalonic acid ). 

In fact, this is not correct Isoprene is not an intermediate, and the discovery of the true pathway started when acetate was, rather surprisingly, found to be the original precursor for all terpenes. The key intermediate is mevalonic acid, formed from three acetate units and usually isolated as its lactone. 

The biosynthesis of roquefortine was investigated by feeding labeled mevalonic acid lactone, tryptophan, and histidine to Penicillium roqueforti these compounds were incorporated (190,191). A biogenetic pathway for roquefortine obtained from Stilton cheese has been suggested (191). 

Kumar, B., Andreatta, C., Koustas, W.T., Cole, W.C., Edwards-Prasad, J., and Prasad, K.N. (2002). Mevastatin induces degeneration and decreases viability of cAMP-induced differentiated neuroblastoma cells in culture by inhibiting proteasome activity, and mevalonic acid lactone prevents these effects. JNeurosci Res 68 627-635. 

In the course of biosynthetic studies on the antibiotic, siccanin (46), Nozoe et al. have not only isolated trans-y-monocyclofarnesol (47) from the mycelia of the fungus, Helminthosporium siccans, but they have also demonstrated that a cell-free enzymatic preparation from the fungi converts mevalonic acid lactone into (47) in high yield. A key intermediate in the synthesis of abscisic acid is (48), which... 

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