Mevinic Acids Research Articles

ChemInform Abstract: The Synthesis of the δ‐Lactone Portion of the Mevinic Acids. A New Non‐Acidic Method of Cyclic Lactone Expansion.

AbstractThe readily available chiral lactone (I) is transformed into the vinylic phenyl sulfide (II) which is cyclized upon methoxymercuration and reduction, producing the tetrahydropyran (IV).

Mevinic acids and analogs : a novel efficient route to chiral synthons from 1,6-anhydro-D-glucose

1,6-anhydro-D-glucose is efficiently and regioselectively deoxygenated at C-2 and C-4 by displacement of the corresponding ditosylate with thiophenol followed by Raney Ni hydrogenolysis. This route provides a short access to chirons of the key lactonic moiety of mevinic acids.

Synthesis and biological evaluation of a monocyclic, fully functional analogue of compactin.

Compound 8, a monocyclic analogue of compactin, has been prepared and its efficacy as an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGR) evaluated. The synthesis (Schemes I and II) requires seven steps starting with di-(-)-menthyl fumarate and employs the useful RR-phosphonate reagent 14 to attach the mevinic acid side chain to aldehyde 13. A molecular mechanics study shows that the preferred conformations of 18 (a model for compactin) and 19 (a model for 8) are nearly identical. Compound 8 inhibits HMGR with IC50 = 320 microM, compared to a corresponding value of 32 nM for the compactin ketone, 5. The factor of 10,000 difference in the two inhibitors corresponds to a difference in binding energy of 5.45 kcal mol-1, or 1.36 kcal mol-1 for each of the four carbons of 5 that are missing in analogue 8. This quantitative difference is consistent with the idea that the decalin moiety of the mevinic acids play a purely hydrophobic role in binding the inhibitors to the enzyme.

Synthesis of optically active mevinic acid subunits via acetal initiated/vinylsilane terminated polyene cyclizations

Efficient routes to optically active octahydronaphthalenol mevinic acid subunits via vinylsilane-mediated polyene cyclizations initiated by trimethylenedioxy acetals are detailed. Enantioselective alkynone reductions and Ireland-Claisen rearrangements serve to establish and transfer absolute stereochemistry.

The synthesis of the δ-lactone portion of the mevinic acids; a new non-acidic method of cyclic lactone expansion

An alkoxy-mercuration demercuration sequence has been used as the key step in an enantiospecific synthesis of a protected synthon for the lactone porton of the mevinic acids.

Chiral synthons for the elaboration of mevinic acid analogues

Baker's yeast reduction of methyl 3-oxo-5-hexenoate (6b) affords the( R )-hydroxy-ester (7b) (76% ee) which is converted into the lactones (15) and epoxy-ester (19), synthons of the lactone part of the mevinic acids.

An Alternative Approach to Mevinic Acid Analogues from Methyl (3 [formula omitted])-3-Hydroxy-5-Hexenoate and an Extension to Rational Syntheses of (+)-(6 [formula omitted])-Goniothalamin and its Non-natural (-)-(6 [formula omitted])-Enantiomer

The chiral mevinic acid analogues [(15) and (16)] have been prepared from the yeast reduction product (2) by homologation and selenolactonistion and subsequently converted into both enantiomers of Goniothalamin [(17) and (18)].

The synthesis of mevinic acids

Article de synthese en 3 parties: synthese totale des mevinoline et compactine; synthese des fragments «hexaline» et «octaline» des composes precedents et de leurs derives dihydrogenes; synthese de la partie lactone

Mevinic acids and analogues: preparation of a key chiral intermediate

The preparation of methyl 3-0-tert-butyldiphenylsilyl-2,4-dideoxy-β- D - erythro - hexopyranoside, a key chiral intermediate for mevinic acids, and its elaboration into four mevinate analogues are described.