Mevinic Acids Research Articles

ChemInform Abstract: Asymmetric Synthesis of the δ‐Lactone Moiety in Mevinic Acid Derivatives Using an Enzymatic Procedure.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The Use of Enzymes for the Preparation of Biologically Active Natural Products and Analogues in Optically Active Form

The enantioselective hydrolysis of chiral esters using esterases and lipases gives access to key optically active intermediates en route to prostaglandins, coriolic acid, the anti-HIV agent carbovir and mevinic acid type hypocholestemic agents. The hydrolysis of meso-esters using hydrolases is a very efficient strategy in organic synthesis and has been used to prepare the carbocyclic nucleosides neplanocin and risteromycin. Acylases have been used to prepare (-)-carbovir and both enantiomers of a GABA-mimetic from 2-azabicyclo[2.2.1)hept-5-en-3-one. The employment of nitrilases and nitrile hydratases is gaining in popularity; for example, prochiral 2-benzoyloxypropane-1,3-dinitrile is hydrolysed to (S)-3-benzoyloxy-4-cyanobutanoic acid with exquisite selectivity. Lipases in organic solvents can effect esterification, transesterification and interesterification reactions and this popular methodology has been used to prepare key norcarbocyclic nucleotides and carbocyclic oxetanocin A in single enantiomer form. Yeast­ catalysed reductions of ketones afford optically active secondary alcohols, typically employed for the synthesis of pheromones, fragrances and chemotactic agents such as leukotriene-84. Instead of a whole-cell system such as yeast, partially purified dehydrogenases can be employed to synthesise (S)-secondary alcohols, for examplan intermediate to the antifungal agent brefeldin-A. Biohydroxylations are important reactions and are being applied to a wide range of substrates. The oxidation of benzene and derivatives to the corresponding cyclohexadiene diols are classic examples and have provided a route to analogues of cyclophellitol. Similarly, mono-oxygenase catalysed Baeyer-Villiger reactions are now well-documented and have furnished intermediates to carbocyclic-AZT, lipoic acid and azadirachtin. Sulfoxides of high optical purity have been prepared by yeast-catalysed oxidation, while enzymes in the transferase and lyase classes have been used to make carbohydrates and amino acids. In conclusion, the science of biotransformations opens up numerous synthetic routes to a wide variety of target molecules that are not easily accessible by other methods of synthetic organic chemistry.

Asymmetric synthesis of the δ-lactone moiety in mevinic acid derivatives using an enzymatic procedure

Asymmetric induction into meso-1,3-diacetoxy-5-cycloheptene 4 by PFL-catalyzed hydrolysis afforded monoacetate (1S,3R)- 5 of 96% enantiomeric excess (e.e), which was converted into a synthetic equivalent 14 of the δ-lactone moiety in mevinic acid derivatives.

Formal total synthesis of an A-seco mevinic acid

Combined use of chemical and enzymatic methods for a short access to the fully functionalized B-ring, the 2′, 1′, 8a, 4a-tetrasubstituted cyclohexene unit, of A-seco mevinic acids is presented.

ChemInform Abstract: Nitrile Hydratase Enzymes in Organic Synthesis: Enantioselective Synthesis of the Lactone Moiety of the Mevinic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Nitrile hydratase enzymes in organic synthesis: Enantioselective synthesis of the lactone moiety of the mevinic acids

(R)-4-Hydroxy-5-cyanopentene (−)-9, a known precursor of the protected lactone moiety of the mevinic acids 1, has been prepared in 9 steps from (S)-3-(benzyloxy)-4-cyanobutanoic acid 5 (88% e.e.), which was obtained by the asymmetric 2 step hydrolysis of 3-benzyloxyglutaronitrile 4 involving the successive activity of a nitrile hydratase and an amidase enzyme.

Chemistry and Biology of the Zaragozic Acids (Squalestatins)

AbstractNew natural products seldom arouse much excitement. However, with their unprecedented and heavily oxygenated molecular structure, and potentially lucrative biological activity, the zaragozic acids (squalestatins) provoked a flurry of activity among academic and industrial chemists and biologists in the early 1990s. Since they are powerful inhibitors of squalene synthase, the enzyme catalyzing the first committed step on the biosynthetic pathway to cholesterol, hopes were high that the zaragozic acids would follow the huge commercial success of the mevinic acids by becoming second‐generation cholesterol‐lowering drugs. The unusual and characteristic 2,8‐dioxabicyclo[3.2.1]octane‐3,4,5‐tricarboxylic acid “core” structure of the zaragozic acids stimulated a large number of diverse synthetic studies, ranging from the traditional to the avant garde. In this review we attempt to bring together for the first time the chemistry and biology of this fascinating class of molecules.

1994 Merck Frosst Award Lecture New strategies for the stereoselective synthesis of natural and unnatural products via organometallic reagents and catalysts

Samarium in the presence of diiodomethane selectively cyclopropanates an allenic alcohol to yield a methylenecyclopropane with modest to excellent diastereoselectivity. The effect of substituents at the carbinol carbon and the allenic carbon on the diastereoselectivity was investigated. A palladium catalyst was shown to promote the intramolecular cycloaddition of the methylenecyclopropane with an electron-deficient alkyne to yield a methylenecyclopentane. The reaction was stereospecific with retention of stereochemistry as proven by X-ray diffraction. Nickel catalysts accelerate the hydroalumination of oxabicyclo[3.2.1]alkenes, leading to bicyclic trialkylalanes. Upon treatment with a Lewis acid (diisobutylaluminum chloride), the trialkylalanes fragment to provide cycloheptenols. This reaction, followed by an enantioselective enzyme-catalyzed esterification, was used as a key step in a synthesis of the mevinic acid lactone. Keywords: methylenecyclopropane, palladium, stereocontrol, oxabicyclic, nickel.

Asymmetric synthesis of the lactone moiety of mevinic acid

Nickel catalyzed reductive ring-opening of oxabicyclic[3.2.1] compound 3 and enzymatic acetylation of cycloheptenol 4 were used as key steps to prepare the (+)-enantiomer of a derivative of mevinic acid lactone.

ChemInform Abstract: Synthesis of Intermediates for the Lactone Moiety of Mevinic Acids via Tellurium Chemistry.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An efficient route to the formal total synthesis of A-seco mevinic acid analogues

An efficient route to the formal total synthesis of A-seco mevinic acid analogues

An efficient route to the formal total synthesis of A-seco mevinic acid analogues

A short, stereocontrolled access to the fully functionalized B-ring together with a chemobiological approach to the 1,2,3,4-tetrasubstituted cyclohexene unit of A-seco mevinic acids is presented.

ChemInform Abstract: Synthesis of Conformationally Restricted Relatives of the Mevinic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Intermediates for the Lactone Moiety of Mevinic Acids via Tellurium Chemistry

Treatment of p-toluenesulfonates of epoxides of specific primary allylic alcohols with telluride ion, prepared in situ by reduction of relatively nontoxic elemental tellurium, installs the two key secondary alcohol functions that occur in the lactone part of the cholesterol-lowering drugs, compactin, mevinolin, and lovastatin. Since the epoxides of the primary allylic alcohol starting materials can be synthesized in optically active form by the Sharpless-Katsuki asymmetric epoxidation (SAE) process, the stereospecific telluride transposition can give optically active secondary allylic alcohols configured for maximum inhibition of cholesterol formation

Synthesis of conformationally restricted relatives of the mevinic acids

Condensations between the tricyclic ketones 9, 19 and 23 and the sodio-lithio dianion of methyl acetoacetate lead to the conformationally restricted Mevinic acid relatives 12b, 20b and 26 respectively, following lactonization and selective reduction. The approach of the nucleophile is stereospecific in the first two instances but not in the last; explanations for this behaviour are given. The target compounds showed negligible HMGCoA reductase antagonism.

Stereoselective synthesis of the tetrasubstituted cyclohexane core of a monocyclic mevinic acid analogue

Stereoselective synthesis of a 1,2,3,4-tetrasubstituted cyclohexane 23, intermediate towards Karanewsky's monocyclic Compactin analogue 3, has been performed starting from levoglucosan 4.

ChemInform Abstract: Enantioselective Synthesis of the Hydroxy‐Lactone Moiety of Mevinic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Stereocontrolled routes to functionalized [1,8-bc]naphthopyran. A study on the total synthesis of quassinoids and tetrahydronaphthalene antibiotics

The intramolecular Diels-Alder reactions of (4E,6E)-1-(5,6-dihydro-5-oxo-2H-pyran-2-yl)-2-methyl-4,6-octadienes have been examined with a planned synthesis of quassinoids, chlorotricholides, and mevinic acids. The intramolecular Diels-Alder reactions of 1-(5-oxo-2H-pyran-2-yl)-2-methylocta-4,6-dien-3-ones preferentially afforded products possessing a trans-ring junction. For 1-(2H-pyran-2-yl)-2-methyl-3-[(thexyldimethylsilyl)oxy]-4,6-octadienes the cyclization was controlled by the methyl at C-2 and led to cis-fused or trans-fused derivatives. The reactions were performed under thermal Lewis acid catalyzed and sonochemical conditions with no changes in the reaction selectivity and reaction yields

Enantioselective synthesis of the hydroxy-lactone moiety of mevinic acids

2-Oxa-4 endo-hydroxybicyclo[3.3.0]-oct-7-en-3-one was resolved with Pseudomonas fluorescens lipase and one of the enantiomers was converted into a key intermediate in the synthesis of mevinic acids.

ChemInform Abstract: Phosphorus‐Containing Inhibitors of HMG‐CoA Reductase. Part 3. Synthesis of Hydroxyphosphinyl Analogues of the Mevinic Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.