Mevinic acid

Using water as the solvent enhanced the rate of the hetero-Diels-Alder reaction relative to the dimerization of cyclopentadiene. In addition, the reaction is much faster at a low pH, which implies that the reaction is acid catalyzed. The 5,5-fused system generated has been used in the total synthesis of several bioactive compounds, including the anti-HIV agent (—)-carbovir (Eq. 12.51)121 and the hydroxylactone moiety of mevinic acids (Eq. 12.52).122... 

Phomopsis sp. strain endophytes of the medicinal plant Erythrina crista-galli continue to yield novel compounds (Table 1). New phenyl-propane, pyronol, benzoic acid, phenylpyran, macrocyclic, and alkene compounds were discovered, as well as the known compounds clavatol, 4-hydroxymellein, mellein, mevalonolactone, mevinic acid, nectriapyrone, phomol, scytalone, and tyrosol. The new compounds were phomopy-ronol (101), 3-phenylpropane-l,2-diol (102), 4-(2,3-dihydroxypropoxy) benzoic acid (103), 2-(hydroxymethyl)-3-propylphenol (104), 2-... 

Endo, A. Hasumi, K. (1997) Mevinic acids. In Fungal Biotechnology. Anke, T. ed.. Chapman Hall, London, pp. 162-72. 

P. Boquel, C. Loustau Cazalet, Y. Chapleur, S. Samreth, and F. Bellamy, An expeditious enantiospecific synthesis of a precursor of the lactonic portion of mevinic acids, Tetrahedron Lett. 33 1997 (1992). 

Y. Chapleur, The chemistry and total synthesis of mevinic acids, in Recent Progress in the Chemistry of Antibiotics, G. Lukacs and S. Ueno, eds., Springer, New York, 1993 pp. 829-937. 

Rhabdomyolysis in a stable renal transplant recipient was attributed to the presence of red yeast rice (Monascus purpureus) in a herbal mixture (116). The condition resolved when he stopped taking the product. Rice fermented with red yeast contains several types of mevinic acids, including monacolin-K, which is identical to lovas-tatin. The authors postulated that the interaction of ciclosporin with these compounds through cytochrome P450 had resulted in the adverse effect. Transplant recipients must be cautioned against using herbal products to lower their lipid concentrations, in order to prevent such complications. 

Lactone ring expansion.1 The 7-lactone 2 can be expanded to the protected y-lactol 4, characteristic of mevinic acids, by reaction of the lactol of 2 with this Wittig reagent to provide a vinyl sulfide 3. Conversion of the vinyl sulfide to 4 was... 

Octahydronapthalene synthesis.1 An intramolecular version of this annelation using a Michael addition to a vinyl sulfone provides the octahydronapthalene unit (1) of compactin (2), a mevinic acid of interest as an inhibitor of cholesterol synthesis. 

In DERA reactions, where acetaldehyde is the donor, products are also themselves aldehydes. In certain cases a second aldol reaction will proceed until a product has been formed that can cyclize to a stable hemiacetal.71 For example, when a-substituted aldehydes were used, containing functionality that could not cyclize to a hemiacetal after the first aldol reaction, these products reacted with a second molecule of acetaldehyde to form 2,4-dideoxyhexoses, which then cyclized to a hemiacetal, preventing further reaction. Oxidation of these materials to the corresponding lactone, provided a rapid entry to the mevinic acids and compactins (Scheme 5.43). Similar sequential aldol reactions have been studied, where two enzyme systems have been employed72 (Scheme 5.44). The synthesis of 5-deoxy ketoses with three substitutents in the axial position was accomplished by the application of DERA and RAMA in one-pot (Scheme 5.44). The long reaction time required for the formation of these thermodynamically less stable products, results in some breakdown of the normally observed stereoselectivity of the DERA and FDP aldolases. In a two-pot procedure, DERA and NeuAc aldolase have... 

Stereoselective trans a-hydroxylation of (5)-dihydro-5-(t-butyldiphenylsiloxymethyl)-2(3/f)-furanone can be realized in good yield by enolization and reaction with the Oxodiperox-ymolybdenum(pyridine)(hexamethylphosphoric triamide) complex (MoOPH) (eq 10). Appropriate manipulation of the resulting trans-hydroxylactone provides 1,3-polyols typified by (18), as well as tetrahydropyran (19) which is a key intermediate in mevinic acid syntheses. ... 

Kiyooka et al. reported that the 3i-catalyzed aldol reaction of a silyl ketene acetal involving a dithiolane moiety with y3-siloxy aldehyde resulted in the production of syn and anti 1,3-diols with complete stereoselectivity depending on the stereochemistry of the catalyst used [45b]. This methodology was applied to the enantioselective synthesis of the optically pure lactone involving a syn-l,3-diol unit, known to be a mevinic acid lactone derivative of the HMG-CoA reductase inhibitors mevinolin and compac-tin (Sch. 2). 

Boquel, P, Chapleur, Y, A new strategy for the synthesis of mevinic acids analogues. Tetrahedron Lett, 31, 1369-1372, 1990. 

Karanewsky, D.S., and Badia, M.C., Phosphorus-containing inhibitors of HMG-CoA reductase. Part 3. Synthesis of hydroxyphosphinyl-analogues of the mevinic acids. Tetrahedron Lett., 34. 39. 1993. 

The aqueous oxa-Diels-Alder reaction has been successfully exploited in the synthesis of sesbanimides A and B [70], carbovir [71], mevinic acids [72], aris-teromycin and carbodine [73], ketodeoxyoctulosonic acid (KDO) and analogs... 

Such an aqueous hetero Diels-Alder reaction, which was extended to other dienes [42], was applied in various syntheses, including sesbanimides A and B [43], carbovir [44], mevinic acids [45], aristeromycin and carbodine [46], ketodeoxyoctu-losonic acid (KDO) and analogs [47], and sialic acids [48]. Pyruvaldehyde, glyoxal, and even ketones like pyruvic acid also react with dienes in water [42],... 

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