Amano AK Research Articles

Chemoenzymatic Synthesis of Primary Alcohols with a 2-Isoxazoline Moiety

Racemic 2-isoxazoline-5-carboxylate esters were reduced under mild conditions to form the corresponding primary alcohols. These alcohols were enzymically resolved by acylation with succinic anhydride in the presence of Amano AK lipase.

Lipase‐Catalyzed Resolutions of both Enantiomers of Ornidazole and Secnidazole

AbstractThe resolutions of both enantiomers of the ornidazole and secnidazole were achieved with high enantiomeric excesses (ee > 99%) by acylation of the corresponding racemates with vinylacetate in the presence of lipase Amano AK (from Pseudomonas sp.). The assignments of the absolute configurations of (+) or (‐)‐ornidazole and secnidazole are described.

Improvement in lipase-catalyzed synthesis of fatty acid methyl esters from sunflower oil

Biodiesel as alkyl esters derived from vegetable oils has considerable advantages in terms of environmental protection. In the present work, methyl esters were produced from sunflower oil by lipase-catalyzed reactions. The effect of organic solvent on alcoholysis rate was investigated and highest conversion (80%) was found in n-hexane and petroleum ether. Among several microbial lipases tested for alcoholysis activity in a solvent-free system, the best conversion (>90%) was found with lipase from Pseudomonas fluorescens (Amano AK) at the highest molar equivalent of oil:methanol (1:4.5). To reduce inactivation of commercial immobilized lipases by methanol, a three-step protocol consisting of the stepwise addition of 1 M equivalent of methanol at 5 h intervals, was developed. Also with immobilized lipase from Rhizomucor miehei (Lipozyme RM IM) high conversion (>80%) was possible. Moreover, the transesterification could be conducted for at least 120 h during five batch runs without significant loss of activity.

The chemistry of Zerumbone IV: Asymmetric synthesis of Zerumbol

The achiral sesquiterpene zerumbone ( 1), readily available from a wild ginger, has unique functionality and reactivity which make it a potential starting material for conversion to useful compounds such as paclitaxel, provided that it can easily be transformed to chiral derivatives. Optically active zerumbol 2 and its acetate 3 were synthesized by lipase-catalyzed stereoselective transesterification of racemic 2. In the best conditions found, a lipase from Pseudomonas fluorescens (Amano AK) and isopropenyl acetate in THF at 30 °C afforded ( R)- 2 and ( S)- 3 with an E value of 56. The absolute configuration of ( R)- 2 was determined by Sharpless epoxidation with l-diethyltartrate ( l-DET) to a bisepoxide of known configuration.

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

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.

Asymmetric synthesis of ( R)-(+)-etomoxir via enzymatic resolution

An asymmetric synthesis of ( R)-(+)-etomoxir 3, employing enzymatic resolution of ethyl 2-alkyl-2,3-dihydroxypropionate using Amano AK via transacylation is reported.

Enzymatic resolution of syn-2-azido-1,3,4-trihydroxybutane catalysed by lipases in the transesterification mode

The enzymatic resolution of both syn-2-azido-1,3,4-trihydroxybutane 1 and syn-2-azido-1,4-diacetoxy-3-hydroxybutane 2 have been undertaken with different lipases as catalysts and vinyl acetate as acylating agent. Lipases Amano PS and Amano AK proved to be the superior catalysts for this resolution. Indeed, both enantiomers of 1 are easily available in good yields and very good e.e.s (up to >99%). The use of chiral HPLC with a Chiralcel OD-H column allowed the determination of e.e.s of both diacetate 2 and triacetate 3 ( syn-2-azido-1,3,4-triacetoxybutane) in a single analysis and thus facilitated the precise control of the reaction.

Lipase-mediated kinetic resolution of allylic(hydroxymethyl)methylenecyclopentane building blocks

Enzymatic-mediated kinetic acylation of allylic(hydroxymethyl)methylenecyclopentane building blocks (±)- 1a, b is reported using various commercially available lipases. Lipase Amano AK ( Pseudomonas sp.) proved to be the best lipase in the case of (−)- 1b which was obtained with a 96% enantiomeric excess. Single crystal X-ray diffraction analysis, using the (1 S,4 R)-camphanate derivative of (−)- 1b, helped us to assign the S absolute configuration of (−)- 1b and the enantiomeric specificity of the tested lipases.

Asymmetric syntheses of nitroalkanols using Pseudomonas sp. lipase: a proposal for the selection of the solvent system of lipase-catalyzed transesterification

By lipase-catalyzed stereoselective transesterification using Amano AK from Pseudomonas sp., nitroalcohols such as 1-nitro-2-butanol and 1-nitro-3-methyl-2-butanol were synthesized enantioselectively with enantiomeric ratios ( E values) of 20.9 and 12.5, respectively, in n-propyl ether. Various results were obtained during the lipase-catalyzed transesterification by changing the organic solvents that were used. The plots of the E values against the reciprocal of the dielectric constants ( ε) of the various organic solvents produced a bell-shaped curve which had a maximum E value for n-propyl ether (1/ ε=0.3). The distance between the enzyme and the substrate might be changed in response to a change in the organic solvent.

Enzymatic desymmetrization of prochiral 2,3-bis(acetoxymethyl)bicyclo[2.2.1]hepta-2,5-diene and 2,3-bis(hydroxymethyl)bicyclo[2.2.1]hepta-2,5-diene

Enzymatic desymmetrization of the title compound 1 is reported using various commercially available lipases in hydrolysis and alcoholysis reactions or ester synthesis. In this area, lipase Amano AK (Pseudomonas sp.) proved to be the best lipase whatever the experimental conditions used. The monoacetate product 2 is indifferently obtained with more than 95% enantiomeric excess (ee) as the levorotatory enantiomer 2a or the dextrorotatory one 2b.

Kinetic resolution of hydroxymethyl-substituted (arene)Cr(CO) 3 and (diene)Fe(CO) 3 by lipase

A kinetic resolution of (η 6-arene)chromium complexes and (η 4-diene)iron complexes by lipase has been developed. Racemic tricarbonyl( o-substituted benzylalcohol)chromium complexes were kinetically resolved to give (1 R)-alcohol complexes and the corresponding (1 S)-acetate complexes, respectively, in high yield and enantioselectivity by transesterification with isopropenyl acetate in the presence of Amano PS or Amano AK. On the other hand, Amano AY recognizes the antipode (1 R)-alcohol complex. Similarly, hydroxymethyl substituted tricarbonyl(2,4-diene)iron complexes produced optically active alcohol and acetate complexes with high enantioselectivity by lipase catalyzed transacetylation.