Jan Plenkiewicz

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

Abstract 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 racemic 3-aryloxy-1-nitrooxypropan-2-ols by lipase-catalyzed enantioselective acetylation

Abstract Both ( R )- and ( S )-enantiomers of 3-aryloxy-1-nitrooxypropan-2-ols ( R )-(−)- 1 , ( S )-(+)- 2 were prepared in high enantiomeric excess by lipase from Pseudomonas cepacia (Amano PS) or Pseudomonas fluorescens (Amano AK)-catalyzed acetylation of racemic alcohols 1a – g with vinyl acetate in n -hexane at 4 or 22°C. The enantioselectivity of this transformation was dependent on the substitution pattern of the aryl ring with E -values ranging from 31 to 111.

Chemoenzymatic Synthesis of Proxyphylline Enantiomers

A novel synthetic route for preparation of proxyphylline enantiomers using a kinetic resolution (KR) procedure as the key step is presented. The reactions were catalyzed by immobilized Candida antarctica lipase B in acetonitrile. Three types of reactions were examined: (i) enantioselective transesterification of racemic proxyphylline with vinyl acetate as well as (ii) hydrolysis and (iii) methanolysis of its esters. The influence of reaction conditions on the substrate conversion and enantiomeric purity of the products were investigated. Studies on analytical scale reactions revealed that the titled API enantiomers could be successfully obtained with excellent enantiomeric excess (up to >99% ee). The process was easily conducted on a 5 g scale at 100 g/L. In a preparative-scale reaction, unreacted (S)-(+)-butanoate (97% ee) and (R)-(-)-alcohol (96% ee) were obtained after 2 days in yields of 45% and 46%, respectively. When the reaction time was extended to 6 days, (S)-(+)-butanoate was isolated in >99% ee and acceptable high enantioselectivity (E = 90). Importantly, the KRs products could be conveniently isolated by exploiting varying solubility of the ester/alcohol in acetonitrile at room temperature. In addition, a chiral preference of the CAL-B active site for the R-enantiomer was rationalized by in sillico docking studies.

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

Summary Racemic 1-(β-hydroxypropyl)azoles were prepared by solvent-free direct regioselective ring opening of 1,2-propylene oxide with imidazole or 1,2,4-triazole. Lipase-catalyzed transesterification of alcohols with vinyl acetate resulted in kinetic enantiomers resolution. Separated (S)-enantiomers of (+)-1-(1H-imidazol-1-yl)propan-2-ol and (+)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol were quaternized with alkyl bromides or iodides, yielding novel optically active ionic liquids. Racemic salts were tested against a wide range of microorganisms.

Lipase-Catalyzed Kinetic Resolution of the Racemic Mixtures of 1-Aryloxy-3-Nitrato-and 1-Aryloxy-3-Azido-2-Propanols

Abstract The racemic mixtures of 1-aryloxy-3-nitrato-2-propanols and 1-aryloxy-3-azido-2-propanols were resolved with moderate selectivity by the lipase-mediated acylation with vinyl acetate. The effects of the nature, position, and spatial requirements of the phenyl-ring substituents on the resolution degree were investigated.

Synthesis of optically active aminooxy alcohols

Racemic secondary alcohols with an N-protected oxyamino function in the β-position were prepared by a base-catalyzed epoxide ring opening with N-hydroxyphthalimide or acetone oxime. The enantiomers were separated with a good selectivity by a lipase-catalyzed acetylation of the racemates with vinyl acetate. The protecting group of the aminooxy alcohol was split off by a hydrochloric acid hydrolysis to yield the hydrochloride of one of the enantiomeric forms of the title compounds.

Preparative scale synthesis of (S)-2-hydroxypropoxyamine hydrochloride

Abstract A simple preparation of ( S )-2-hydroxypropoxyamine hydrochloride by bakers yeast reduction of prochiral N -(2-oxopropoxy)phthalimide followed by acid hydrolysis is described.

Synthesis and Lipase-Catalyzed Acetylation of N-[(2-Alkoxycarbonyl)Benzoyl]-4-Hydroxyisoxazolidines

Abstract Several N-[(2-alkoxycarbonyl)benzoyl]-4-hydroxyisoxazolidines were prepared as the racemic mixtures, and resolved by the lipase-mediated acylation.

Lipase-Mediated Resolutions of 1-Aryl-3-Buten-1-ols

Abstract Racemic mixtures of 1-aryl-3-buten-1-ols were separated with high enantioselectivity by a lipase-mediated acetylation with vinyl acetate. The effects of the nature, position, and spatial requirements of the phenyl-ring substituents on the separation efficacy were investigated.

LIPASE-CATALYZED ACETYLATION OF tert-BUTYL N-(2-HYDROXY-3-PHENOXYPROPOXY)CARBAMATES—PREPARATION OF OPTICALLY ACTIVE AMINOOXYPROPANOLS

ABSTRACT A simple method was developed for the preparation of optically active-3-aryloxy-1-aminooxy-2-propanols by a lipase-catalyzed kinetic resolution of racemic mixtures of their N-tert-butylcarbamate-protected derivatives.