Methyl Mevalonolactone

Finally, natural (i )-(-)-mevalonolactone, a key intermediate from a broad spectrum of cellular biological processes and their regulation, was synthesised via eight steps in 55% overall yield and > 99% ee (Scheme 19). In the key step, the aforementioned enantioconvergent chemoenzymatic deracemization route was applied. Thus, 2-methyl-2-benzyl-oxirane ( )-2 g was deracemized on a large scale (10 g) using lyophilized cells of Nocardia EHl and sulfuric... 

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... 

The biosynthesis of virginiamycin Ml in Streptomyces virginiae has been studied using both radiolabeled precursors (63) and stable isotope techniques (45, 63-65). Incorporation of [2-l4C]acetate, L-[methyl-3H]methionine, dl-3-14C]serine, L-[3,4-3H2]proline, and [2-14C]glycine established these compounds as the main precursors (63). The assumption that carbons 2, 26, 27, and 28 arose from valine was supported by the observation that no incorporation of appropriately labeled mevalonolactone was observed (65). On the basis of the radio-... 

The Reformatsky reactions of methyl or ethyl bromoacetate with 4-acetoxy-,2,24 4-benzyloxy-,2 4-tetrahydropyranyloxy-,2 4-chloro-,8 and 4,4-dimethoxy-2-butanone1418 have been carried out. The adducts were converted to mevalonolactone by hydrolysis and, in the case of the acetal reactant, by appropriate reduction and oxidation procedures. The same Reformatsky-type syntheses of mevalonolactone have also been performed using the lithium and magnesium carbanions of acetate esters5,19 25 26 and the dianion of acetic acid28,27 instead of the usual zinc reagent. The intramolecular Reformatsky reaction of 4-(bromoacetoxy)-2-butanone gives mevalonolactone directly.28 A related route to mevalonolactone involves boron trifluoride-catalyzed cycloaddition of ketene to 4-acetoxy-2-butanone followed by hydrolysis.183... 

Many of the procedures given above have been utilized for the preparation of mevalonolactone labeled with isotopes of carbon, hydrogen, and oxygen.7-9 Mevalonolactone-14C has been prepared with the label at all six positions l-,7 29 2-,7 143 24 3-,llb 3 -, 203,30 4-,7,183 and 5-14C.19 Preparations of singly and doubly labeled meva-lonolactone-13C have been reported recently 2-,26,31 3-,32 4-,33 3, 4-,7,183 3,4-,26,33b and 4,5-13C.34 The procedure described here26 for the preparation of mevalonolactone-2-13C is both convenient and economical compared to the usual Reformatsky methods since acetic acid-2-13C is utilized directly in the condensation reaction, rather than methyl or ethyl bromoacetate. The overall yield of mevalonolactone-2-13C is 46-52% based on acetic acid-2-13C. 

S) -( — )-2-Methyl-2-hydroxy-y-butyrolactone (176a) is a useful synthon for the asymmetric construction of acyclic tertiary a-hydroxy acids found in natural products such as the pheromone frontalin and mevalonolactone, the biosynthetic precursor of terpenoids and steroids. This compound is readily prepared from lactone (175) using the asymmetric enolate oxidation protocol and dimethoxy oxaziridine ( + )-(158) <95JOC6l48>. The a-hydroxy lactone (176b), isolated as the benzoate, was obtained in 84% ee and 70% yield. A single crystallization from ethyl acetate improved the ee to >94% (Equation (41)). 

Methyl vinyl ketone, 31-32, 225, 676, 697-703, 887, 970, 974,1112 Methyl a- and /5-xylopyranoside, 834 DL-Mevalonic acid 5-phosphate, 811 Mevalonolactone, 146, 809-810 (R and S), 809 Michael reaction, 1069 Mitomycin, 941 Mobay, 1171 Molecular rotations, 297 Molecular sieves, 333, 431, 703-705, 739 Mondur TD-80,1171 Monobromopentaerythritol, 450 Monochlorourea, 1107,1267 Monoethylamme-borane, 16 Monoethyl raalonate, 523 Monomethylamine-borane, 16 Monoperoxytucdnic acid, an Penuodnlc acid... 

The oxidation was used in a new synthesis of ( )-mevalonolactone (3) from 4-methyl-l, 6-heptadiene-4-ol (1). 

A)-Mevalonolactone [mevalolactone, (/ )-tetrahy-dro-4-hydroxy-4-methyl-2A/-pyran-2-one]. 

Based on the CPO-catalyzed stereoselective epoxidation of terminal alkenes, Lakner et al. designed a concise synthetic route for the preparation of the natural lactone (R)-mevalonolactone 27 (Scheme 13.5). The key step of the sequence was the epoxidation of ethyl 3-methyl-3-butenoate catalyze by CPO, which yielded the corresponding (R)-24 in 67% yield and 93% ee. Tlie final product was achieved in 57% overall yield and identical purity (Scheme 13.5) [87]. 

Figure 6.69 Reformatsky approach to the synthesis of racemic [2- C ]mevalonolactone from methyl bromo[2d C]acetate...

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