Mevalonolactone synthesis

Metronidazole — see also Imidazole, l-(2-hydroxy-ethyl)-2-methyl-5-nitro-antiprotozoal activity, 1, 180 veterinary use, 1, 208 mode of action, 1, 208 Metyrapol metabolism, 1, 234 Metyrapone metabolism, 1, 234 Mevaloladone synthesis, 1, 490 Mevalonolactone synthesis, 3, 846 MG18755... 

HLADH oxidation of 3-methylpentane-l,3,5-triol yields, after silver oxide oxidation, (35)-(-l-)-mevalonolactone of 14% optical purity/" The synthesis of [4,5- C2]MVA using known procedures was omitted from last year s Report, " " and another synthesis of ( )-mevalonolactone has been reported. " ... 

In view of the importance of mevalonate in the biosynthesis of terpenes and steroids, it is not surprising that numerous syntheses of mevalonolactone are available. These are briefly itemized in the detailed procedure for the synthesis of (i ,S)-mevalonolactone labelled at C-2 with 13C (Scheme 215) (81OS(60)92>. 

Lakner FJ, Hager LP (1996) Chloroperoxidase as Enantioselective Epoxidation Catalyst An Efficient Synthesis of (R)-(-)-Mevalonolactone. J Org Chem 61 3923... 

CPO has been used occasionally in complex syntheses. An important application of CPO as an enantioselective epoxidation catalyst is the efficient synthesis of (R)-2-mevalonolactone (Scheme 2.26a) [270]. A survey of the literature revealed that the previous methods required many steps to produce the lactone, in low overall yield, with moderate ee, in addition to expensive starting materials. Meanwhile, a retro-synthetic analysis starting with an appropriately functionalized epoxide provided confidence that CPO could rescue the situation if used in the key stereogenic step. Another completed synthesis is depicted in Scheme 2.26b. Again, the epoxide is generated in high yield with conversion to (R)-dimethyl-2-methylaziridine-l,2-dicarboxylate, which may serve as a synthon for P-methylamino acids [283],... 

M. Fetizon, M. Golfier, and J. M. Louis, Highly selective oxidations of diols by silver carbonate, Chem. Commun., (1969) 1102 A new synthesis of lactones application to ( )-mevalonolactone, ibid., (1969) 1118-1119. 

The typical secondary metabolites of soft corals are diterpenoids, although some species also produce sesquiterpenoids. The sesquiterpene portion of furoquinol (Structure 2.102) is labeled by [2-3H]mevalonolactone in Sinularia capillosa,m while Heteroxenia sp. converts acetate and meva-lonate into cubebol (Structure 2.103) and clavukerin A (Structure 2.104).188 In contrast, acetate is used for cetyl palmitate synthesis in Alcyonium molle, but not for de novo diterpene biosynthesis.188... 

Until recently, chemical and enzymatic approaches toward the synthesis of enantiomerically enriched aldols have been applied almost exclusively to the synthesis of secondary aldols. Conversely, we found no general methods, either chemical or enzymic, for the preparation of enantiomerically enriched tertiary aldols, even though tertiary aldols are structural motifs common to many bioactive natural products, such as Vineomyci-none B2 (14), Dicrotaline (15), Torosachrysone (16), Mevalonolactone (17), and Mycarose (18). Application of natural enzymes toward the synthesis of enantiomerically enriched tertiary aldols might partially be hindered by the fact that no known natural aldolase catalyzes the synthesis of tertiary aldols (List et al., 1999). 

Synthesis of labelled mevalonolactones continues to receive attention,47,72 and new syntheses of ( )-, (R)-, and (S)-mevalonolactones have been reported.73 The isolation74 of the energy-rich carboxylic ester (23) of prenyl mercaptan prompts the... 

Enzymes from Gluconobacter roseus organisms proved somewhat less venatile, but did allow a simple enantioselective synthesis, of the unnatural enantiomer of mevalonolactone (35 Scheme 13) in reasonable optical purity. ... 

Pig Liver Esterase (PLE). This is the more used car-boxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1, CAS 9016-18-6) which physiologically catalyzes the hydrolysis of carboxylic acid esters to the free acid anion and alcohol. PLE is a serine hydrolase which has been widely used for the preparation of chiral synthons and these applications have been fully reviewed. An active-site model for interpreting and predicting the specificity of the enzyme has been published. In the pioneering studies of the enzyme applications field, PLE was used for the chiral synthesis of mevalonolactone. Prochiral 3-substituted glutaric acid diesters... 

Hydrolases - Chymotrypsin is the best documented hydrolase. It has a very broad and predictable stereospecificlty and is widely used in resolution of racemic esters.1 L-DOPA has been prepared in this way.41 Several esterases also exhibit enantiotopic specificity. This is exploited in the synthesis of R-mevalonolactone 22 from 21.42... 

Fig. 5. Synthesis of (R)-mevalonolactone through stereoselective bioepoxidation of methallyl-propionate using chloroperoxidase [91]...

Eguchi, T. Morita, M., and Kakinuma, K., Multigram synthesis of mevalonolactone-rf, and its application to stereochemical analysis by H NMR of the saturation reaction in the biosynthesis of the 2,3-di-O-phytanyl-5 -glycerol core of the Archaeal membrane lipid, 7. Am. Chem. Soc., 120, 5427, 1998. 

I he last two examples show that acid-sensitive functional groups can be present. The reaction was used in a convenient synthesis of ( )-mevalonolactone (11, The Grignard reaction of ethyl acetate and allylmagnesium bromide gives the tertiary alcohol (1). This was ozonized and the crude ozonide reduced with... 

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