Lactones mevinic acid

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). 

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... 

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). 

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. 

S)-Hydro3grmethyl-5-valerolactone (18) has been made firom D-mannitol via isopropylidene-D-glyceraIdehyde.2i Epoxides of type (19) can be made in a few steps from triacetyl-D-glucal, and provide intermediates for the lactone ring of the mevinic acids, as demonstrated by their conversion to (20) with benzyl magnesium chloride.22... 

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... 

Scheme 45 Preparation of a synthetic equivalent for the 5-lactone in mevinic acids...

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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