G. D. Gamalevich

A versatile and convenient protocol for the stereocontrolled synthesis of olefinic insect pheromones

A combination of the Horner-Emmons synthesis of alkyl 2,4-dienoates with their hydrogenation over complex L.Cr(CO)3 catalysts (L = 3CO or arene) provides a versatile, stereocontrolled and operationally simple approach to the (Z)-disubstituted, (Z)-trisubstituted, (E)-trisubstituted alkenes and skipped (Z,Z)-disubstituted diolefins with a homoallylic type of functionally. This protocol, sometimes supplemented by an enzymatic hydrolysis, was successfully applied to the synthesis of configurationally pure (gp > or = 98%) pheromones of the furniture carpet beetle, dry bean beetle, rusty grain beetle, square-necked grain beetle and a trail-following pheromone mimic for subterranean termites.

Enantioselectivity of enzymatic acylation of some structurally various racemic alcohols in anhydrous aprotic media

Partial acylation of (R,S)-3,7-dimethyloctan-1-ol (1) and (R,S)-7-methoxy-3,7-dimethyloctan-1-ol (2) with vinyl acetate catalyzed by the lipase fromCandida cylindracea affords in good yields the correspondingS-configured acetates with 92–98% enantiomeric excess (ee). Under similar conditions, racemic α-cyclogeraniol (3), drim-7-en-11-ol, methyl 4-(3-hydroxy-2-methylpropyl)benzoate, and its η6-chromium(tricarbonyl) complex (6) are acylated with rather poor (and, for the two latter, opposite) enantioselectivity, whereas (R,S)-2,4∶3,5-di-O-benzylidenexylitol remains unaffected. Racemic isoborneol (8) and 2-nitro-1-phenylethanol also remain almost or completely unconverted. Attempts to perform enantioselective acylation of alcohols 3 and 8 with Ac2O in the presence of porcine pancreatic lipase (PPL) proved equally unsuccessful. By contrast, the PPL-catalyzed acylation of alcohol 6 with vinyl acetate at 17% conversion affords the levorotatory acetate (S)-6a withca. 100%ee. PPL-Mediated partial acylation of (R,S)-pantolactone with Ac2O, followed by mild deacylation of the resultingR acetate, gives (R)-(-)-pantolactone of 97% enantiomeric purity in 60% overall yield.

Lipase-mediated deracemization of secondary 1-phenyl-substituted propargylic alcohols of different topology

Acetylation of (±)-1-phenylnon-2-yn-1-ol, (±)-1-phenylhept-1-yn-3-ol, and (±)-1-phenylundec-4-yn-3-ol ((±)-5) in the presence of lipase from Candida cylindracea (CCL) proceeds slowly to give products with ee ≤20%. The acetates of these alcohols are hydrolyzed in the presence of porcine pancreatic lipase (PPL) equally unsatisfactorily. The (η6-arene)tricarbonylchromium complex of alcohol (±)-5 is acetylated in the presence of CCL up to ∼22% conversion to give (R)-acetate whose oxidative decomplexation followed by saponification results in alcohol (R)-(–)-5 with ee ≥95%. The configuration of alcohols (–)-5 and (+)-5 was determined by NMR spectroscopy of their esters with (R)- and (S)-Moshers acids.

2,5,6,7,8-Pentasubstituted (S)- and (R)-[2-chroman-2-yl]ethanols as intermediates for the synthesis of α-tocopherol and its chiral analogs

In the presence of lipase from the yeast Candida cylindracea, partial acetylation of (±)-2-[6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl]ethanol with vinyl acetate gives S-(+)-acetate whose alkaline hydrolysis affords (S)-(–)-alcohol. Repeated enzymatic acetylation of the “residual” alcohol up to ∼39% conversion afforded the R-enantiomer. The enantiomeric alcohols were oxidized to (S)- or (R)-aldehydes having the same sign of [α]D as the original alcohols. These alcohols were converted into S-(+)- and R-(–)-enantiomers of the antioxidant MDL-73404, a hydrophilic analog of α-tocopherol.

Lipase-mediated ‘meso-tricks’ to transform latently symmetrical d-aldoses into l-aldoses via alditols

Abstract l -Fucose and l -xylose were synthesized from dulcitol and xylitol, respectively, using CCL- or PPL-mediated kinetic resolution as the key step. In the first case dissymmetrization was achieved directly by acylating a meso derivative, while in the second it was preceded by the conversion of the meso polyol into a racemic intermediate.

New ways to determine the absolute configurations of alkyl 6-R-cyclohexa-1,3-dienecarboxylates

Two new methods for the determinatuion of the absolute configuration of methyl 4-methyl-6-(2-methylprop-1-enyl)cyclohexa-1,3-dienecarboxylate are proposed, and the configurations attributed previously to its (+)- and (–)-enantiometers are confirmed. Chiral methyl carboxylate is converted into the corresponding alcohol whose configuration is deduced from either the rate of hydrolysis of the respective racemic acetate in the presence of pancreatic lipase (method 1) or from the difference between the Eu(fod)3-induced shifts of the MeO signals in the 1H NMR spectra of the diastereomeric esters of S- or R-Moshers acid (method 2).

Terpenes in organic synthesis

A seven-step synthesis ofS-(+)-hydroprene (S-1) in ∼20 % overall yield starting fromS-(+)-3,7-dimethyl-1,6-octadiene (2) of 55+-10 % optical purity is described. The introduction of an optical enhancement step in the synthetic sequence at the stage ofS-(−)-3,7-dimethyl-1-octanol (9) raises the optical purity ofS-1 from ∼50 % to ∼80 %.

The absolute configuration of (+)- and (−)-1-phenylundec-4-yn-3-ols. Synthesis of ( R )-4-dodecanolide, a component of the defensive secretion of rove beetle Bledius mandibullaris

Hydrogenation of the triple bond of (+)-1-phenylundec-4-yn-3-ol (obtained from (+)-[η6-(3-hydroxyundec-4-yn-1-yl)benzene]chromium tricarbonyl) with the NaBH4-NiCl2·6H2O reagent system in MeOH leads to (−)-1-phenylundecan-3-ol. Ozonolysis of the phenyl ring in the corresponding acetate gives (R)-(−)-acetoxydodecanoic acid, lactonization of which leads to the known (R)-(+)-4-dodecanolide. The starting (+)-1-phenylundec-4-yn-3-ol was thus shown to have the S-configuration.

Enantioselective transesterification of (±)-1-phenylundecan-3-ol catalyzed by the lipase from Burkholderia cepacia

Enantiomerically enriched (R)- and (S)-1-phenylundecan-3-ols were obtained by kinetic resolution of the racemate with vinyl acetate in ButOMe at 20 °C using the lipase from Burkholderia cepacia. The absolute configuration of the enantiomers was confirmed by a direct stereochemical correlation with the known (R)- and (S)-dodecanolides.

Chiral Analogs of a-tocopherol. Antioxidant Activity of the ( R ) and ( S ) Enantiomers of {2-[6-hydroxy-2,5,7,8-tetramethylchroman-2-yl]ethyl}-trimethylammonium- p -toluenesulfonate Depending on Their Configuration

Starting with the (R) and (S) enantiomers of 2-(6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)ethanol, prepared previously by partial acylation of the corresponding racemic alcohol in the presence of the most easily available lipase, from the yeast Candida cylindracea, a four-stage syntheses was developed for both enantiomers of {2-[6-hydroxy-2,5,7,8-tetramethylchroman-2-yl]ethyl}trimethylammonium p-toluenesulfonate (MDL-73404), which are chiral analogs of α-tocopherol. Comparative biomedical testing of samples of MDL-73404 salts with different enantiomer compositions in relation to their effects on the generation of reactive oxygen species by peritoneal macrophages from white rats in systems containing luminol or lucigenin demonstrated different levels of inhibition of spontaneous and 12-O-myristyl-13-O-acetylphorbol-activated macrophage chemiluminescence.