Lactone Portion Research Articles

Total Synthesis of Biselide E, a Marine Polyketide.

The total synthesis of biselide E, a marine polyketide isolated from the Okinawan ascidian, has been accomplished. The highlight of this approach is the use of the β-elimination reaction of the chloroacetoxy group for the construction of an unstable six-membered α,β,γ,δ-unsaturated lactone portion at the late stage of the total synthesis.

ChemInform Abstract: Enantioselective Synthesis of the Lactone Moiety of the Mevinic Acids Using D-Xylose as a Chiral Precursor.

Homologation of the lactone 14 easily obtained from D-xylose afforded the pyranone 15, a key chiral synthon for the lactone portion of mevinic acids.

Stereoselective Construction of the Tricyclic Core of Neoliacinic Acid

The tricyclic core of the plant-derived sesquiterpene natural product neoliacinic acid was synthesized using a novel synthetic strategy. The pivotal synthetic transformations are construction of the key bicyclic ether-bridged intermediate by sequential deployment of metal carbenoid C-H insertion and ylide-forming reactions and installation of the lactone portion of neoliacinic acid by an acid-catalyzed intramolecular ring-opening reaction of an epoxide with a carboxylic acid.

Synthesis of the Tetracyclic Bis(acetal) Lactone Portion of Saudin

AbstractTwo synthetic approaches towards the synthesis of the tetracyclic lactone 4, containing the caged bis(acetalic) backbone of Saudin, were explored. Both sequences included the utilization of the known epoxy‐acetal 3, prepared stereoselectively by means of an intramolecular radical cyclization, as the common key intermediate, allowing total control over the relative stereochemistry of four consecutive chiral centers. Oxidative degradation with ruthenium dioxide and unsymmetrical ozonolysis reactions provided the new two key synthons in each synthetic route. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Improvement in 193 nm Photoresists Performance by 172 nm VUV Curing

In order to make the enhancement of dry etching durability of methacrylate-based ArF resists induced by VUV curing consistent with low film shrinkage, i.e., less CD deviation, characteristics of several methacrylate-based polymers were studied. It was found that the film shrinkage mainly depended on the side chain structures and polymers containing acrylate group in main chain and norbornane lactone group in side chain portion showed dry etching resistance equal to commercially available KrF resists with lower film shrinkage than methacrylate-based ArF resists by VUV curing and suitable for the process. Curing reaction mechanism of methacrylate-based polymers were also studied using an infrared micro spectrometry with gradient shaving preparation. It was confirmed that the linkage radiolysis around carbonyl sites, mainly lactone portion of methacrylate-based ArF resist polymers induced by 15sec VUV light irradiation proceeded from the film surface to the interface with the substrate. VUV curing less than 1 minute was noticed to be effective for improvement in methacrylate-based ArF resists performance and might be met with the process tact time required for mass production phase.

Determination and distribution of 6-methoxymellein in fresh and processed carrot puree by a rapid spectrophotometric assay.

Isocoumarin or 6-methoxymellein (6-MM) was extracted from carrot tissue using alkali saponification to solubilize the lactone portion of its structure into an aqueous phase. Acidification and subsequent organic solvent extraction allowed isolates to be quantified and verified as 6-MM by spectrophotometric determination. 6-Methoxymellein was analyzed in carrot cross sections, as a function of depth and before and after thermal processing. A natural propensity for 6-MM accumulation was observed in root tip sections exposed to ethylene, and levels increased as a result of wounding. Consecutive layer peeling demonstrated that small-diameter roots accumulated greater amounts of 6-MM in periderm tissue compared to large roots. Processing carrots into a puree resulted in 10-25% greater extraction of 6-MM than grinding fresh carrot samples, whereas steam-cooked and thermally processed purees had 15% greater extraction than unheated purees. This analytical technique will allow carrot processors to accurately estimate raw and processed products for the bitter compound 6-MM.

Total synthesis of isodeoxypodophyllotoxin using the Me3Sn radical initiated carbocyclization

The lactone portion of the podophylotoxin framework was assembled from a free-radical carbocyclization reaction, and the target structure was constructed based on intramolecular Friedel–Crafts reaction. In addition to isodeoxypodophyllotoxin, there were formed unusual tri- and tetracyclic compounds. Key words: free-radical carbocyclization, C—Sn bond cleavage, podophyllotoxin analog.

Deglycosylated Products of Endogenous Digoxin-like Immunoreactive Factor in Mammalian Tissue

Digoxin-like immunoreactive factor (DLIF) from adrenal cortex is an endogenous molecule with structural features remarkably similar to those of digoxin, a plant-derived cardiac glycoside (Shaikh, I. M., Lau, B. W. C., Siegfried, B. A., and Valdes, R., Jr. (1991) J. Biol. Chem. 266, 13672-13678). Two characteristic structural and functional features of digoxin are a lactone ring and three digitoxose sugars attached to a steroid nucleus. Digoxin is known to undergo deglycosylation during metabolism in humans. We now demonstrate the existence of several naturally occurring deglycosylated components of DLIF in human serum. The components are identified as DLIF-genin, DLIF-mono, and DLIF-bis, corresponding to the aglycone, and the aglycone with one and two sugars, respectively. Similar components are produced by acid-induced deglycosylation of DLIF isolated from bovine adrenal cortex. The elution pattern and sequence of DLIF-deglycosylation was identical to that of digoxin suggesting identical sugar stoichiometry. However, analysis of these newly discovered congeners by reverse-phase chromatography, spectrophotometry, antibody reactivity, and kinetics of deglycosylation, demonstrates that subtle structural and physical differences do exist when compared to digoxin. DLIF was chromatographically distinct from digoxin, and interestingly, the mobility of the DLIF-genin was shifted toward increased polarity relative to digoxigenin. DLIF and DLIF-bis, -mono, and -genin congeners have absorbance maxima at 216 nm, whereas digoxin and its congeners absorb at 220 nm. Reaction with specific antibodies directed at the lactone portion of these molecules shows DLIF and its deglycosylated congeners to be 10(3)-fold less reactive than digoxin. Kinetics of sugar removal suggests that DLIF is 8-fold more susceptible to deglycosylation than is digoxin. Two less polar DLIF components produced from the DLIF-genin have lambdamax at 196 nm and are 4-fold less immunoreactive than DLIF. Our data suggest that subtle structural differences exist between DLIF and digoxin at or near the lactone ring as well as in the nature of the sugars. The presence of deglycosylated congeners of DLIF in human serum, including the less polar components, suggests in vivo deglycosylation of these factors. This is the first demonstration of the existence of naturally occurring deglycosylated derivatives of DLIF and establishes the likelihood of active metabolism of DLIF in mammals.

Synthesis of Tuckolide, a New Cholesterol Biosynthesis Inhibitor.

Tuckolide (decarestrictine D), a 10-membered lactone isolated from P. corylophilum and polyporus tuberaster fungi that potently inhibits cholesterol biosynthesis, was synthesized. The key steps include a Sharpless catalytic asymmetric dihydroxylation reaction (AD) of the methoxymethyl (MOM) ether protected diene 2 and a direct Corey-Nicolaou lactonization reaction of seco-acid 1with added silver perchlorate. The selectivity of the dihydroxylation step was found to be highly dependent on the nature of the protecting group adjacent to the diene in 2. The selectivity of the asymmetric dihydroxylation reaction of 2 indicates that both steric and electronic effects can lead to significant amounts of the undesired isomers. This synthesis establishes the absolute stereochemistry of tuckolide showing the C3 hydroxyl bearing carbon with an S-configuration comparable in an absolute sense to that in the lactone portion of the HMG-CoA reductase inhibitor compactin.

Molecular characterization and cloning of an esterase which inactivates the macrolide toxin brefeldin A.

The macrolide antibiotic brefeldin A (BFA) was described as a phytotoxin and pathogenicity factor from Alternaria carthami Chowdhury, the causal agent of a devastating blight disease in safflower (Carthamus tinctorius L.). The toxin is known to inhibit the endoplasmic reticulum-Golgi flux and processing. Conventional breeding of safflower for resistance to the Alternaria blight disease has failed, and in situ detoxification of brefeldin A is a novel approach for the protection of field-grown safflower plants from the blight disease. As a first step towards this goal, a strain of Bacillus subtilis has been isolated which is capable of hydrolyzing brefeldin A to a non-toxic metabolite, brefeldin A acid. The BFA esterase was purified to homogeneity from B. subtilis extracts and shown to consist of a monomeric peptide of approximately 40 kDa. Besides brefeldin A, the esterase hydrolyzed ethyl valerate, which structurally resembles the lactone portion in the brefeldin A molecule, but failed to accept other macrolides such as erythromycin or zearalenone. Roughly 12% of the esterase sequence was identified by microsequencing tryptic peptides and the N terminus, which lacked a methionine leader residue. Corresponding oligonucleotide probes were employed to clone the esterase gene in pUC18. One of seven clones was sequenced and shown to code for the full size esterase protein of 372 amino acid residues. The esterase gene was subcloned in pT7-7 and expressed in Escherichia coli yielding a fusion protein with a specific esterase activity 3-fold over that of the enzyme purified from B. subtilis. The cloned esterase provides the basis for the generation of transgenic safflower plants as a valuable asset in the research on nonspecific phytotoxins and in supporting breeding for Alternaria blight resistance.

Synthesis of one of the major mouse metabolites of lovastatin and simvastatin

An unequivocal synthesis of the mouse liver metabolites of lovastatin and simbastatin resulting from β-oxidation of the lactone portion is described.

ChemInform Abstract: Enantioselective Hetero‐Diels‐Alder Reaction with Glyoxylate Catalyzed by Chiral Titanium Complex: Asymmetric Synthesis of the Lactone Portion of Mevinolin and Compactin.

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.

ChemInform Abstract: Diastereoselective Synthesis of the Lactone Portion of Compactin and Mevinolin.

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.

Enantioselective Hetero-Diels-Alder reaction with glyoxylate catalyzed by chiral titanium complex: asymmetric synthesis of the lactone portion of mevinolin and compactin

Asymmetric Diels-Alder reaction with methyl glyoxylate catalyzed by the chiral titanium complex 1 provides the dihydropyran carboxylate in high enantiomeric purity, which can be converted to the lactone portion of mevinolin or compactin.

ChemInform Abstract: Synthesis of Enantiomeric Pure Intermediate for the Lactone Portion of Compactin and Mevinolin.

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.

Enantioselective synthesis of the lactone moiety of the mevinic acids using D-xylose as a chiral precursor

Homologation of the lactone 14 easily obtained from D-xylose afforded the pyranone 15, a key chiral synthon for the lactone portion of mevinic acids.

Synthetic studies on the mevinic acids using the chiron approach: total synthesis of (+)-dihydromevinolin

A general strategy for the synthesis of the mevinic acids starting from L-glutamic acid as a chiral template is presented. The octahydronaphthalene ring system of dihydromevinolin and mevinolin is constructed from an intramolecular Diels-Alder cycloaddition involving a butenolide. The lactone portion is elaborated from a cyclopentanone by a Baeyer-Villiger oxidation with bis(trimethylsilyl) peroxide

Diastereoselective synthesis of the lactone portion of compactin and mevinolin

The highly diastereoselective [4 + 2] cycloaddition of 1-methoxybuta-1,3-diene (3) to (2R)-N-glyoxyloylbornane-10,2-sultam (2) afforded the adduct (4) which was effectively transformed into (4R,6S)-4-hydroxy-6-hydroxymethyltetrahydro-2-pyrone (1), a key synthon for the lactone moiety of compactin and mevinolin.

Synthesis of enantiomeric pure intermediate for the lactone portion of compactin and mevinolin

A diastereo and enantioselective synthesis of compound 11 a potential useful intermediate for the lactone portion of mevinolin and compactin was developed. Our strategy is based on the high stereoselective Michael addition of alkoxide to chiral norephedrine-derived oxazolidine 4.

A Facile Chiral Synthesis of the Lactone Moiety of Compactin and Mevinolin from (R)-O-Benzylglycidol

A facile chiral synthesis of (4R,6S)-4-hydroxy-6-hydroxymethyltetrahydro-2-pyrone a key synthon, for the lactone portion of compactin and mevinolin, is established