An enantioselective synthesis and biobehavioral evaluation of 7-fluoro-3-(p-fluorophenyl)-2-propyltropanes

Optically pure 7-fluorotropanes 3a-c, were synthesized as structural probes of the dopamine transporter. The synthesis of these compounds was accomplished through the asymmetric 1,3-dipolar cycloaddition reaction of the oxidopyridinium betaine 4 with the chiral dipolarophile (R)-p-tolyl vinyl sulfoxide. In the preliminary analysis, tropane 3a was found to reduce the rewarding effects of cocaine in the brain stimulation reward paradigm.     

A novel enantioselective synthesis of (S)-(-)- and (R)-(+)-nornicotine via alkylation of a chiral 2-hydroxy-3-pinanone ketimine template

An asymmetric synthesis of the optically pure isomers of the minor tobacco alkaloid and CNS nicotine metabolite, nornicotine, has been achieved with moderately high optical purity. The synthetic pathway involves alkylation of a chiral ketimine, prepared from either 1R,2R,5R-(+)- or 1S,2S,5S-(-)-2-hydroxy-3-pinanone and 3-(aminomethyl)pyridine with 3-bromopropan-1-ol. After cleavage of the respective C-alkylated ketimines with NH2OH.HCl, and treatment of the resulting amino alcohols with HBr, followed by base-catalyzed intramolecular ring closure, (S)-(-)-nornicotine and (R)-(+)-nornicotine were obtained with ee values of 91% and 81%, respectively.     

An enantioselective synthesis of (+)-(S)-[n]-gingerols via the l-proline-catalyzed aldol reaction

An enantioselective approach to (+)-(S)-[n]-gingerols (1a–c) has been developed. The requisite stereogenic centers of target molecules are facilely constructed by the proline-catalyzed cross-aldol reaction from readily available achiral starting materials.     

Novel lipase-catalysed enantioselective deacetylation of (+/-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine

(+/-)-5-Acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine has been synthesised by a highly diastereoselective [3+2] cycloaddition reaction between alpha-(4-fluorophenyl)-N-phenylnitrone and vinyl acetate in good yield. Candida rugosa lipase catalyses the deacetylation of this (+/-)-5-acetoxyisoxazolidine in a highly enantioselective fashion in diisopropyl ether containing n-butanol affording (-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine in 43% yield and >99% ee.     

Short and simple synthesis of (R)- and (S)-4-hydroxypentylaminoacetamide: both enantiomers of the (ω-1)-hydroxylated metabolite of milacemide

Both (R)- and (S)-4-hydroxypentylaminoacetamide have been synthesized by reductive amination of glycinamide on the γ-valerolactols corresponding to (R)- and (S)-γ-valerolactone, respectively. These enantiomeric lactones were readily obtained in high enantiomeric excess (ee) by enzymic porcine pancreatic lipase (PPL) kinetic resolution of rac-methyl γ-hydroxyvalerate. © 1992 Wiley-Liss, Inc.     

Carnitine and trimethylaminobutyrate synthesis in rat tissues (Short Communication)

Liver and testis slices convert 6-N-trimethyl-lysine into 4-N-trimethylaminobutyrate and carnitine. Adipose, skeletal muscle, heart, or kidney tissues metabolize trimethyl-lysine into trimethylaminobutyrate but not into carnitine. Trimethylaminobutyrate hydroxylation, forming carnitine, occurs in liver and to a minor degree in testis. Liver is the primary site of carnitine biosynthesis in the rat.     

Optimization of enantioselective synthesis of methyl (R)-2-chloromandelate by whole cells of Saccharomyces cerevisiae

Methyl (R)-2-chloromandelate, a key intermediate in the synthesis of clopidogrel, was obtained by the reduction of methyl-2-chlorobenzoylformate using whole cells of Saccharomyces cerevisiae. A 100% conversion and 96.1% of enantiomeric excess (ee) value was obtained when 17 methyl-2-chlorobenzoylformate/l was reacted with 8 g S. cerevisiae/l and 83 g glucose/l at pH 7.     

来源于西梅的(R)-醇腈酶促立体选择性转氰合成(R)-酮醇腈

在水/有机溶剂双相反应体系中,研究了来源于西梅的(R)-醇腈酶催化酮与丙酮醇腈合成(R)-酮醇腈的立体选择性转氰反应．系统探讨了不同酶源、酶粉颗粒大小、底物浓度、两底物配比、酶浓度和底物结构对转氰反应的影响．结果发现西梅醇腈酶能高效催化三甲基硅酮与丙酮醇腈的立体选择性转氰．酶粉颗粒大小以直径0.3～0.45 mm为优,底物浓度以21 mmol/L左右为佳,底物丙酮醇腈与三甲基硅酮摩尔浓度比以2∶1为宜,酶浓度以60.9 g/L左右为好．西梅醇腈酶对3, 3-二甲基-2-丁酮几乎没有催化活性,而对其硅结构类似物三甲基硅酮却具有非常高的立体选择性和催化活性,在上述优化反应条件下反应24 h的底物转化率和产物光学纯度均高达99%以上,表明底物中的硅原子对西梅醇腈酶的催化活性有非常显著的促进作用．     

Stereospecific synthesis of (-)-neplanocin F

The stereospecific synthesis of (-)-neplanocin F was achieved in 15 steps from 2,3-O-isopropylidene-D-1,4-ribonolactone. The synthetic methodology can give an access through appropriate modifications to new series of carbanucleosides.     

Possible site of flavonoid synthesis in the photosynthetic apparatus (Short Communication)

Chloroplasts were prepared in aqueous suspension from buckwheat (Fagopyrum esculentum Moench.) seedlings, and the incorporation of [1-(14)C]acetic acid into quercetin (3,5,7,3',4'-pentahydroxyflavone) by the isolated chloroplast preparations was investigated.     

Preferential synthesis of a membrane-associated protein by free polyribosomes (Short Communication)

Isolated free polyribosomes from rat liver appear to synthesize NADPH–cytochome c reductase in vitro four times as efficiently as do membrane-bound polyribosomes. The observed synthesis by the latter could result from contamination with free polyribosomes, but an alternative explanation is also suggested.     

Enantiospecific synthesis of carbocyclic (+)-(E)-5-(2-bromovinyl)-2'-deoxyuridine

(+)-1-[(1R, 3S, 4R)-3-hydroxy-4-hydroxymethylcyclopentyl]-5-[(E)-2- bromovinyl]-1H,3H-pyrimidin-2,4-dione 10 was synthesized starting from (+)-endo-5-norbornen-2-yl acetate. This chiral educt was obtained by enzymatic hydrolysis of racemic esters of endo-5-norbornen-2-ol.     

Lipase B from Candida antarctica catalyses enantioselective transesterification of 2-(4-methoxybenzyl)-1-cyclohexanols and 2-(4-methoxybenzyl)-1-cyclopentanols

The 2-(4-methoxybenzyl)-1-cyclohexanols and 2-(4-methoxybenzyl)-1-cyclopentanols are the basic structure of a series of juvenile hormone analogs which act as insect growth regulators. Their enantioselective transesterification with the lipase B from Candida antarctica produced pure enantiomers of R-cyclohexyl and R-cyclopentyl acetates (i.e. ee_p > 99%). Differences observed in the resolution of the four racemic compounds are in accordance with model structure of secondary alcohols suitable for catalysis.     

(Z)-3-(fluoromethyl)phosphoenolpyruvate: synthesis and enzymatic studies

(Z)-3-(Fluoromethyl)phosphoenolpyruvate has been synthesized in nine chemical steps from glyoxylic acid. The compound is stable at pH 3, but at pH 8 it decomposes within seconds to give 2-oxo-3-butenoate. When 3-(fluoromethyl)phosphoenolpyruvate is added to a solution of phosphoenolpyruvate carboxylase or pyruvate kinase, the enzyme is inactivated over the course of an hour. Identical kinetics of inactivation are observed whether the reaction is initiated by addition of 3-(fluoromethyl)-phosphoenolpyruvate, preformed 2-oxo-3-butenoate, or 4-fluoro-2-oxobutanoate (which rapidly undergoes elimination of fluoride ion to form 2-oxo-3-butenoate). The inactivating species in all cases is believed to be 2-oxo-3-butenoate. The inactivation is completely prevented by the presence of dithiothreitol, which reacts rapidly with 2-oxo-3-butenoate. Studies with competitive inhibitors of both enzymes indicate that inactivation does not occur at the active site.     

The determination of (-)-(S)- and (+)-(R)-ifosfamide in plasma using enantioselective gas chromatography: a validated assay for pharmacokinetic and clinical studies

An enantioselective gas chromatographic method has been developed and validated for the determination of the plasma concentration of the enantiomers of the anticancer drug ifosfamide (IFF). In this approach, the IFF enantiomers are separated from the plasma matrix by solid phase extraction, chromatographically resolved by gas chromatography on a chiral stationary phase, and detected by mass selective detection using selective ion monitoring. The assay has been validated for routine clinical and pharmacokinetic use and has a limit of detection in plasma of 250 ng/ml of each isomer.     

Solid-phase synthesis of sauvagine-(17-40)

The solid-phase synthesis of the tetracosapeptide corresponding to the C-terminal amino acid sequence of sauvagine is described. After purification by gel filtration, the polypeptide appeared to possess an acceptable degree of homogeneity, as judged by different kinds of electrophoresis and chromatography, and by automated Edman degradation analysis. Preliminary pharmacological results indicate that the fragment-(17-40) is practically devoid of any sauvagine activity on the circulatory system and endocrine glands; a weak effect on gastric emptying delay has been demonstrated (1% of the natural product).     

New synthesis of (+)-(S)-halothane

A new synthesis of non-racemic halothane (1-bromo-1-chloro-2,2,2-trifluoroethane) is reported. The stereospecificity of the key reaction, decarboxylation of a salt of optically enriched 1-bromo-1-chloro-2,2,2-trifluoropropionic acid to give halothane, is shown to be highly dependent on the nature of the cation. When the cation is trialkylammonium, a high level of stereospecificity is observed. © 1996 Wiley-Liss, Inc.     

An enantioselective synthesis of insecticidal 4-alkynyloxazolines

2-(2,6-Difluorophenyl)-4-phenylalkynyl oxazolines are potent insect growth regulators. An efficient and enantioselective synthesis to these compounds has been developed which relies on a (-)-sparteine mediated hydroxymethylation of the lithium dianion of propargylic amides.     

Highly enantioselective synthesis, crystal structure, and circular dichroism spectroscopy of (R)-bambuterol hydrochloride

The present article describes the asymmetric synthesis of (R)-bambuterol hydrochloride based on 1-(3,5-dihydroxyphenyl)ethanone as starting material, which was esterified by dimethylcarbamic chloride, and brominated by copper (II) bromide. Then the carbonyl group was reduced efficiently using (-)-B-chlorodiisopinocamphenylborane [(-)-DIP-chloridetrade mark] as an asymmetrical reducing agent. Followed by epoxide ring closure with NaOH and ring expansion with tert-butylamine led to the desired product (R)-bambuterol with e.e. up to 99%. The optical properties and absolute configuration of (R)-bambuterol hydrochloride were further investigated using circular dichroism spectroscopy and X-ray single crystal analysis.