Resolution of racemic 1-azido-3-aryloxy-2-propanols by lipase-catalyzed enantioselective acetylation

Kinetic resolution of racemic 1-azido-3-aryloxy-2-propanols 1a–g was performed using supported lipase of Candida antarctica-B (Novozym^® SP 435) in toluene at 4°C with isopropenyl acetate as the acyl donor to afford the optically active (S)-alcohols 2a–g and their corresponding (R)-acetates 3a–g with E values from 56 to 72.     

Resolution of 2-aryloxy-1-propanols via lipase-catalyzed enantioselective acylation in organic media

2-Aryloxy-1-propanols, primary alcohols with an oxygen atom at the stereocenter, were resolved with good to high enantioselectivity by acylation with vinyl butanoate mediated by Pseudomonas sp. lipase in di-iso-propyl ether. Potential factors affecting the enantioselectivity of the enzymatic acylation were examined: solvents, acyl donors and temperature. Using this enantioselective acylation procedure, enantiomerically pure (R)-2-(4-chlorophenoxy)-1-propanol was prepared on a gram scale.     

Resolution of non-protein amino acids via Carica papaya lipase-catalyzed enantioselective transesterification

Carica papaya lipase-catalyzed transesterification of the 2,2,2-trifluoroethyl esters of N-benzyloxycarbonylated dl-amino acids carrying aliphatic side chains proceeded smoothly and, in almost all the cases, enantiospecifically (E = >200), affording the l-methyl esters and leaving the d-trifluoroethyl esters intact.     

Resolution of an iridoid synthon, gastrolactol, by means of dynamic acetylation and lipase-catalyzed alcoholysis

A short synthetic route to asymmetric iridoids was developed. The three key steps were an intramolecular [4 + 2] cycloaddition reaction of an enamine derivative of 8-oxocitral (2), a dynamic acetylation, and an enzymatic resolution of the gastrolactyl acetates 5a and 5b, iridoids with three stereocenters. Some regio- and stereoselective heterogeneous catalytic hydrogenations of double bonds in iridoid aglucones were discussed.     

Enantioselective Synthesis of 3-Heterosubstituted-2-amino-1-ols by Sequential Metal-Free Diene Aziridination/Kinetic Resolution

A general protocol for the enantioselective synthesis of 3-heterosubstituted-2-amino-1-ols was developed based on metal- free intramolecular regio- and stereoselective diene aziridination and regioselective opening. Kinetic resolution of the resulting (1′-NR¹R² and 1′-SR)-4-oxazolidinones was performed using ABCs organocatalysts, expanding the application of this methodology.     

Synthesis of enantiomerically pure 3-aryloxy-2-hydroxypropanoic acids,intermediate products in the synthesis of cis-4-Aminochroman-3-ols

Oxidation of accessible (R)-3-chloropropane-1,2-diol to (R)-3-chloro-2-hydroxypropanoic acid and subsequent reaction of the latter with ortho-substituted sodium phenoxide gave a number of enantiomerically pure 3-aryloxy-2-hydroxypropanoic acid which are intermediate products in the synthesis of nonracemic 4-aminochroman-3-ols.     

Kinetic resolution of fluorinated propargyl alcohols by lipase-catalyzed enantioselective transesterification

In order to obtain optically active fluorinated propargyl alcohols, a lipase-catalyzed kinetic resolution has been carried out. The effect of lipase types, organic solvents, reaction temperature, and acyl donors was examined in the lipase-catalyzed transesterification of 1,1,1-trifluoro-4-phenyl-3-butyn-2-ol. Various enantiomerically pure fluorinated propargyl alcohols have been successfully prepared in good enantiomeric excess (>84%) by Novozym 435-catalyzed transesterification with vinyl butanoate at 60 °C in n-hexane. In some cases, the enantiomeric purities were excellent (>99% ee).     

Resolution of racemic 2-amino-1-butanol with immobilised penicillin G acylase

Racemic 2-amino-1-butanol has been resolved to obtain (S)-2-amino-1-butanol with >99% e.e. via enantioselective hydrolysis of its N-phenylacetyl derivative with penicillin G acylase immobilised on Eupergit C.     

Resolution of racemic substances by liquid ion-exchange

Two optically active liquid anion-exchangers have been synthesized. The separation factors of the enantiomers of sodium (+/-)-mandelate and sodium-N-acetyl-(+/-)-alanate have been determined by batchwise equilibration of aqueous solutions of the salts with chloroform solutions of each of the exchangers. Sodium mandelate has been resolved by Craig countercurrent extraction with one of these exchangers. Optically pure products can be obtained even though the liquid ion-exchanger is not optically pure.     

Some properties of 2-alkoxy-1-alken-3-ols

Conclusions The reaction of 2-alkoxyacroleins with Grignard reagent gave some new 2-alkoxy-1-alken-3-ols, which in the presence of p-toluenesulfonic acid are cyclodimerized to 2,3,5,6-tetraalkyl-2,5-dialkoxy-1,4-dioxanes, which tend to cleave ethanol to give 2,3,5,6-tetraalkyl-5-alkoxy-1,4-dioxenes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2534–2538, November, 1980.The authors express their gratitude to V. I. Lavrent'ev and V. Yu. Vitkovskii for taking the mass spectra.     

A catalytic highly enantioselective direct synthesis of 2-bromo-2-nitroalkan-1-ols through a Henry reaction

Highly enantiomerically enriched 2-bromo-2-nitroalkan-1-ols are prepared by direct condensation of aliphatic and aromatic aldehydes with bromonitromethane in the presence of a catalytic amount of copper(ii) acetate and a C(1)-symmetric camphor-derived amino pyridine ligand.     

Resolution of racemic gossypol

The resolution of gossypol for the purpose of comparing the biologic action of (-)-gossypol with its naturally occurring antipode has attracted the attention of scientists. Recently the 1st successful resolution accomplished by chromatographic separation of the hexa-acetates of the condensation products of (+)-gossypol with (S)-1-methylphenethylamine followed by acid hydrolysis of the 2 main hexa-acetate, to give (+)- and (-)-gossypol with identical mp and alpha D values, was reported. Treatment of racemic gossypol with either (R)- or (S)-methylphenethylamine afforded yellow solids with mp 197-200 degrees C and m/z 753 (M + 1)+. By quick chromatography of the condensation products of either the (S) or (R) amine with (+)-gossypol on a silica column with diethyl ether-light petroleum as eluant, pure compounds were obtained. The compounds were assigned as (S)-amino-(+)-gossypol and (R)-amino-(-)-gossypol. These gossypols contained less than 5% of their antipodes. Although different in their antifertility action, the (+ or -), (+), and (-) isomers of gossypol demonstrate the same degree of inhibitory activity against the enzyme lactate dehydrogenase-X. Comparison of the antifertility action of the 3 isomers in male rats revealed that (-)-gossypol in half the dose of the (+ or -) isomer showed comparable activity, while the (+)-gossypol proved to be inactive.     

Synthesis of 1-alkyl-2-methylazetidin-3-ones and 1-alkyl-2-methylazetidin-3-ols

Several 1-alkyl-2-methylazetidin-3-ones were prepared in good yield by the hydride-induced cyclization of the corresponding β-bromo-α,α-dimethoxyketimines, the resulting 3,3-dimethoxyazetidines being hydrolyzed by acid. Imination of these 1,2-disubstituted azetidin-3-ones, followed by alkylation under kinetic control conditions resulted in regioisomeric mixtures of 2,4- and 2,2-dialkylated compounds. Analytical samples of the major 2,4-disubstituted derivatives were obtained after extensive chromatographic separation. The cis stereochemistry of the major 2,4-dialkylated isomer was demonstrated on the basis of NMR data.     

Resolution of cis-2-fluorocyclopropanecarboxylic acid by a microbial enantioselective hydrolysis

The important key intermediate of quinolone analogue synthesis, (1S,2S)-2-fluorocyclopropanecarboxylic acid, was prepared enantioselectively by a microbial resolution. One of the strains with the highest enzymatic specificity was selected from soil and when lyophilized cells were treated with corresponding ester, the remaining (1S,2S)-ester was obtained with high enantiomeric purity (98% e.e.).     

Resolution of racemic 2-isobornyl-4-methylphenol into enantiomers

Resolution of racemic 2-isobornyl-4-methylphenol into enantiomers was performed following its transformation into diastereomers by the reaction with (1S)-camphanoyl chloride.     

Synthesis of 2-dialkylaminomethyltetrahydrofuran-3-ols

The reaction of esters of 4-R-3-methyl-2,3,4,5-diepoxyvaleric acids with secondary amines leads to the formation of esters of 4-R-5-dialkylamino-4-hydroxy-3-methyl-2,3-epoxyvaleric acids. The reduction of the latter with lithium tetrahydroaluminate and the cyclization of the reduction products in the presence of p-toluenesulfonic acid has given 2-dialkylaminoethyltetrahydrofuran-3-ols, the methiodides of which possess ganglion-blocking activity.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1443–1446, November, 1973.     

Microbially mediated enantioselective hydrolysis of racemic acetates

The enantioselective hydrolyses of a series of racemic hydroaromatic acetates by $\text{Rhizopus}$$\text{nigricans}$ to produce optically active alcohols are described. A rule predicting the absolute stereochemistry of the resulting alcohols is proposed.     

Resolution of racemic cis-1-amino-2-indanol by diastereomeric salt formation with (S)-2-phenylpropionic acid

Resolution of racemic cis-1-amino-2-indanol 1, a key intermediate for the synthesis of indinavir, is reported. The conditions were optimized for an industrial-scale resolution of racemic cis-1 using (S)-2-phenylpropionic acid 6 as the resolving agent and ethanol as the solvent. The less-soluble diastereomeric salt, (1R,2S)-1·(S)-6, was obtained in 35% yield with 99% de (E >69%) by crystallization. Resolving agent 6 was efficiently recovered from the salt and the mother liquor.     

A New and Facile Synthesis of Chroman-3-ols, 3,4-Dihydro-2H-[1]-Benzopyran-3-ols

o-Allyl phenols react with m-chloroperoxybenzoic acid (m-CPBA) in dry chloroform to give chroman-3-ols in a single step in good yields (93–96%).