Mevinic acids synthesis

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... 

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. 

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... 

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... 

A review on the synthesis of mevinic acids such as compactin (1)... 

A., Willetts, A.J., and Crosby, ). (1996) Nitrile hydratase enTymes in organic synthesis enantioselective synthesis of the lactone moiety of the mevinic acids. Tetrahedron Lett., 37, 6001-6004. 

A one-carbon ring expansion of y-lactone (37) was used in a synthesis of the intermediate (38) required for mevinic acid syntheses. An ester enolate Claisen rearrangement of the glucose-derived bis(enol ether) (39) gave product (40). used for the synthesis of (+)-streptolic acid (41).4i... 

A review of syntheses of the Prelog-Djerassi lactonic acid includes carbohydrate-based routes,27 and there have been two further reports of syntheses of the P-hydroxy-5-lactone unit (38) of mevinic acid and its congeners.28, 29 jn a synthesis of the mosquito oviposition pheromone (39), the chiral centres were derived from those of 2,3-0-ethylidene-D-erythrose, with this chiron being extended by Wittig reactions, in a similar manner to the use of 2-deoxy-D-ribose in an earlier approach to the same target (S.-K. Kang and I.-H. Cho, Tetrahedron Lett., 1989, 30, 743). 

The lactone moiety 6 found in mevinic acids has been synthesized from L-malic acid using a chiral sulfoxide reagent to control the stereochemistry at C-3. Synthesis of the negamycin lactone 7 has been reported, while a lactone precursor of L-acosamine and L-daunosamine is discussed in Chapter 9. 

Scheme 15 Synthesis of the p-hydroxy-6-lactone framework of mevinic acid...

Shimizu et al. have reported the synthesis of the 4-hydroxy-6-lactone component of mevinic acid by lactonization of a 6-hydroxy ester [53] (Scheme 16). Reaction of lithio-fcrt-butylacetate with p-trichloromethyl-p-lactone 80 gave 6-hydroxy-p-keto ester 81. A stereoselective syn reduction of the ketone, lactcmization, and protection of the secOTidaiy alcohol provided the lactone. The trichloromethyl group was reduced with tri- -butyltin hydride to furnish 6-chloromethyl lactone intermediate 84. 

Synthesis of a synthetic equivalent of the 8-lactone in mevinic acids has been reported by Suemune et al. [89] (Scheme 45). Asymmetric hydrolysis of diacetate... 

Kumar and Dittmer have reported the synthesis of intermediates for the lactone moiety of mevinic acids using tellurium-induced nucleophilic reduction developed by their own group as the key step [122] (Scheme 75). Alcohol 331 was protected and converted into aldehyde 332, which upon Wittig reaction and reduction gave allylic alcohol 333. Sharpless epoxidation of 333 and tosylation of the primary alcohol afforded tosylate 334, which underwent the tellurium-induced transposition providing lactone 335 through spontaneous lactonization. However, in the case of the corresponding fcrf-butyl ester, there was no spontaneous lactonization observed. 

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