Enantiomerically pure piperazines via NaBH4/I2 reduction of cyclic amides

Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (3S,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure l-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine.     

Chiral terpene auxiliaries IV: new monoterpene PHOX ligands and their application in the catalytic asymmetric transfer hydrogenation of ketones

New PHOX ligands, derived in three steps from (1R,2S,3R,5R)-3-amino-apopinan-2-ol 1 and (1R,2R,3S,5R)-3-amino-pinan-2-ol 2 were applied as chiral ligands for the formation of ruthenium catalysts. The catalysts were used in asymmetric transfer hydrogenations of prochiral ketones producing the corresponding alcohols in moderate to high yields and enantioselectivity.     

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.     

Spectaline and iso-6 cassine,two new piperidin 3-ol alkaloids from the leaves of cassia spectabilis

From the leaves of an african leguminosae: Cassia spectabilis DC, we have isolated two unprecedented piperidin 3-ol alkaloids. By spectral data, their structures were elucidated as follows (+)Spectaline(l): 2(S)-methyl 6(R)-(13'-oxotetradecyl)piperidin 3(S)-ol and (-)iso-6-cassine(2) 2(R)-methyl 6(R)-(11'-oxodecyl) piperidin 3(R)-ol.     

Stereoselective synthesis of (R)- and (S)-Ipsdienols, pheromone components of bark beetles of the Ips family

(R)- and (S)-Ipsdienols, components of pheromones of bark beetles of the Ips family, were synthesized with high enantiomeric purity (>98%) from 8-chloro-2-methyl-6-methylideneoct-2-en-4-ol prepared from ethyl 3-chloropropionate via cyclopropanation according to Kulinkovich. 8-Chloro-2-methyl-6-methylideneoct-2-en-4-ol was converted into the corresponding hydrogen phthalate whose stereoisomeric salts with (R)- and (S)-1-phenylethanamines were separated by crystallization, and subsequent hydrolysis of the latter and dehydrohalogenation with potassium tert-butoxide gave targeted (R)- and (S)-ipsdienols.     

Prunus armeniaca hydroxynitrile lyase (ParsHNL)-catalyzed asymmetric synthesis of cyanohydrins from sterically demanding aromatic aldehydes

Herein we report the biocatalytic asymmetric synthesis of cyanohydrins by using a new (R)-HNL from Prunus armeniaca. Several sterically demanding aromatic aldehydes which have never been used as substrates for any known HNLs are employed for the new (R)-HNL from P. armeniaca. The cyanohydrins synthesized are obtained in good chemical yield with excellent enantioselectivities.     

Enantioselective hydrolysis of (RS)-2-fluoroarylacetonitriles using nitrilase from Arabidopsis thaliana

The enzymatic resolution of 2-fluoroarylacetonitriles (RS)-3 using nitrilase from the plant Arabidopsis thaliana is described. Racemic 2-fluoronitriles 3 are easily accessible from O-silylated aromatic cyanohydrins 2 by reaction with DAST. The nitriles (RS)-3 were hydrolysed with the nitrilase as a catalyst, not to the expected 2-fluoroarylacetic acids but to the corresponding (R)-2-fluoroarylacetamides (R)-5 as the main products. After optimization of reaction conditions (pH 9, 7°C), the enantiomeric excesses of (R)-5a,c and f (R=H, 3-Me, 3-OMe) could be improved to >99% by one recrystallization. The acid catalysed hydrolysis of (R)-5a,5c and 5f afforded the corresponding (R)-2-fluoroarylacetic acids (R)-4a,4c and 4f without racemization.     

Synthesis of optically active forms of seudenol,the pheromone of douglas fir beetle

(R)-(+)-Seudenol (3-methylcyclohex-2-en-1-ol) and its antipode were synthesized from optically active forms of 3-iodocyclohex-2-en-1-ol by treatment with Me₂CuLi. Their absolute configurations were determined by converting (+)-3-iodocyclohex-2-en-1-ol to the known (R)-(+)-cyclohex-2-en-1-ol.     

Synthesis of new chiral Schiff bases and their application in the asymmetric trimethylsilylcyanation of aromatic aldehydes

The new chiral Schiff base ligands 1a–1c were synthesized from (1R)-(+)-camphor and found to be efficient catalysts for the enantioselective silylcyanation of aromatic aldehydes. The corresponding aromatic cyanohydrins were obtained in good yields and with enantiomeric excesses (e.e.s) of up to 73%.     

Enzymatic acylation reactions on ω-hydroxycyanohydrins

The enzymatic acylation of certain ω-hydroxycyanohydrins protected at the primary alcohol has been studied. The best enantioselectivities are obtained with Pseudomonas cepacia lipase (PSL-C) and Candida antarctica lipase A (CAL-A), for the ω-O-tritylated cyanohydrins. The effect of the protecting group in the enzymatic reactions has been studied using molecular modeling.     

Cyclopropane intermediates in the synthesis of chiral alcohols with methyl-branched carbon skeleton. Application in the synthesis of insect pheromones

Several chiral building blocks, (2R)-2-methylundec-10-en-1-ol, (3R)-3-methylheptan-1-ol, and (4R)-4-methyloctan-1-ol, have been synthesized using cyclopropane intermediate products. It has been shown that the obtained chiral alcohols can be used in the synthesis of insect pheromones.     

Stereoselective synthesis of biologically active tetronic acids

(4R)-3-Amino-4-trimethylsilyloxy-2-alkenoates (R)-3, obtained from O-trimethylsilyl protected optically active cyanohydrins (R)-1 via the Blaise reaction, are hydrolyzed under mildly acidic conditions to give optically active tetronic acids (R)-4 without racemization. From the follow-up reactions of (R)-4 investigated, only methylation with diazomethane afforded the biologically active tetronic acid derivative (R)-5a without racemization whereas acylation and reductive alkylation, respectively, resulted in partial racemization or failed on the whole.     

Candida antarctica lipase A in the dynamic resolution of novel furylbenzotiazol-based cyanohydrin acetates

A series of novel (R)-furylbenzotiazol-based cyanohydrin acetates were prepared in over 90% isolated yields from the corresponding furancarbaldehydes. The one-pot method combines a basic resin to produce hydrogen cyanide from acetone cyanohydrin, an equilibrium between the formation and decomposition of furylbenzotiazol-based cyanohydrins and the unique enantioselectivity of Candida antarctica lipase A, allowing the acylation of (R)-cyanohydrins in the presence of vinyl acetate in anhydrous acetonitrile.     

PmHNL catalyzed synthesis of (R)-cyanohydrins derived from aliphatic aldehydes

Hydroxynitrile lyase from the Japanese apricot (Prunus mume) catalyzes the formation of several aliphatic cyanohydrins in an asymmetric fashion. By employing a biphasic reaction system, aliphatic aldehydes with various structural features can be converted to the corresponding (R)-cyanohydrins with good overall yield and enantiomeric excess.     

Chemoenzymatic synthesis of glycosylated enantiomerically pure 4-pentene 1,2- and 1,3-diol derivatives

1-Dimethylthexylsiloxy-2-chloroacetoxy-4-pentene 2 and 1-dimethylthexylsiloxy-3-chloroacetoxy-4-pentene 3 were saponified with Pseudomonas lipase to give (R)-1-dimethylthexylsiloxy-4-pentene-2-ol (ee=99%) and (S)-2 (ee=99%) and (S)-1-dimethylthexylsiloxy-4-pentene-3-ol (ee=99%) and (R)-3 (ee=98%), respectively. All enantiomers were chemically transformed into the corresponding enatiomerically pure 2-benzoyloxy-4-pentene-1-ols 8 and 3-benzoyloxy-4-pentene-1-ols 14, respectively. Mannosylation of (R)-8 and (S)-14 with 2,3,4,6-tetra-O-benzoyl-a-d-mannopyranosyl trichloroacetimidate afforded the corresponding mannopyranosides.     

Autoxidation of isotachysterol

Isotachysterol, the acid-catalyzed isomerization product of vitamin D₃, produces seven previously unknown oxygenation products in a self-initiated autoxidation reaction under atmospheric oxygen in the dark at ambient temperature. They are (5R)-5,10-epoxy-9,10-secocholesta-6,8(14)-dien-3β-ol (6a), (5S)-5,10-epoxy-9,10-secocholesta-6,8(14)-dien-3β-ol (6b), (10R)-9,10-secocholesta-5,7,14-trien-3β,10-diol (7a), (10S)-9,10-secocholesta-5,7,14-trien-3β,10-diol (7b), (7R,10R)-7,10-epoxy-9,10-secocholesta-5,8(14)-dien-3β-ol (8), 5,10-epidioxyisotachysterol (9) and 3,10-epoxy-5-oxo-5,10-seco-9,10-secocholesta-6,8(14)-dien-10-ol (10). The formation of these products is explained in terms of free radical peroxidation chemistry.     

Chiral terpene auxiliaries II. Spiroborate esters derived from α-pinene—new catalysts for asymmetric borane reduction of prochiral ketones

New spiroborate esters derived from (1R,2R,3S,5R)-3-aminopinan-2-ol and ethylene glycol, propane-1,3-diol, pinacol, catechol, (1S,2S,3R,5S)-pinane-2,3-diol, and (1R,2R,3S,5R)-pinane-2,3-diol were used as catalysts in the borane reduction of acetophenone and other prochiral aryl alkyl ketones producing the corresponding alcohols in high yields. The influence of the spiroborate structure on the enantioselectivity and configuration of the product alcohols was examined.     

Absolute configuration of (−)-4-methylheptan-3-ol,a pheromone of the smaller european elm bark beetle,as determined by the synthesis of its (3R,4R)-(+)- and (3S,4R)-(+)-isomers

Nerol and geraniol were stereoselectively converted to (±)-threo- and (±)-erythro-4-methylheptan-3-ol respectively. (R)-(+)-Citronellic acid was converted to a mixture of (3R,4R)-(+)-threo- and (3S,4R)-(+)-erythro-isomers which was separable by GLC. These syntheses established the absolute configuration of the naturally occurring (?)-4-methylheptan-3-ol to be 3S,4S.     

Production of Enantiopure Chiral Epoxides with E. coli Expressing Styrene Monooxygenase

Styrene monooxygenases are a group of highly selective enzymes able to catalyse the epoxidation of alkenes to corresponding chiral epoxides in excellent enantiopurity. Chiral compounds containing oxirane ring or products of their hydrolysis represent key building blocks and precursors in organic synthesis in the pharmaceutical industry, and many of them are produced on an industrial scale. Two-component recombinant styrene monooxygenase (SMO) from Marinobacterium litorale was expressed as a fused protein (StyAL2StyB) in Escherichia coli BL21(DE3). By high cell density fermentation, 35 g_DCW/L of biomass with overexpressed SMO was produced. SMO exhibited excellent stability, broad substrate specificity, and enantioselectivity, as it remained active for months and converted a group of alkenes to corresponding chiral epoxides in high enantiomeric excess (˃95–99% ee). Optically pure (S)-4-chlorostyrene oxide, (S)-allylbenzene oxide, (2R,5R)-1,2:5,6-diepoxyhexane, 2-(3-bromopropyl)oxirane, and (S)-4-(oxiran-2-yl)butan-1-ol were prepared by whole-cell SMO.     

Practical synthesis of (E)- and (Z)-2-silyl-3-penten-1-ols with high enantiopurity

Practical methods for the synthesis of the optically active (E)- and (Z)-2-silyl-3-pentene-1-ols are described. The optically pure (E)-allylsilane was synthesized from commercially available (R)-3-butyn-2-ol in five steps involving hydrozirconation followed by alkylation of the resulting alkenylmetal with BnOCH₂Cl. On the other hand, both enantiomers of the corresponding (Z)-allylsilane were prepared from commercially available dimethylphenylvinylsilane through epoxidation, the regioselective epoxide-opening reaction with 1-propynylmagnesium bromide, and the subsequent optical resolution using a lipase.