Arie L. Gutman

Enzymatic lactonisation of γ-hydroxyesters in organic solvents: synthesis of optically pure γ-methylbutyrolactones and γ-phenylbutyrolactone

Abstract Porcine pancreatic lipase in anhydrous organic solvents catalyses the lactonisation of a number of esters of γ-hydroxyacids in nearly quantitative yields. This enzymatic process was used for the highly stereoselective synthesis of (S)-(−)-γ-methylbutyrolactone, (R)-(+)-γ-methylbutyrolactone and of optically active γ-phenylbutyrolactone.

Convenient practical resolution of racemic alkyl-aryl alcohols via enzymatic acylation with succinic anhydride in organic solvents

Abstract Enantiomerically pure alkyl-aryl secondary alcohols were conveniently obtained on a kilogram scale from their racemic mixtures by enzymatic acylation with succinic anhydride in organic solvents. A major advantage of this acylation method is the ease of separating the ester from the unreacted alcohol. This is achieved by extracting the organic solution with aqueous NaHCO 3 after the enzymatic reaction is completed.

Enzymatic oligomerisation versus lactonisation of ω -hydroxyesters

Abstract Porcine pancreatic lipase in anhydrous organic solvents catalyses almost exclusively the oligomerisation reaction of unsubstituted β, δ, and e-hydroxyacid methyl esters. In Contrast, the substituted δ-methyl- δ-hydroxyester undergoes lactonisation.

Enzymatic formation of lactams in organic solvents

Abstract Porcine pancreatic lipase in organic solvents catalyses the intramolecular cyclisation of aminoesters and the formation of macrocyclic bislactams from diesters and diamines.

Selective hydrolysis of dinitriles into cyano-carboxylic acids by Rhodococcus rhodochrous N.C.I.B. 11216

SummaryA soil bacterium Rhodococcus rhodochrous N.C.I.B. 11216 attained high growth rates with either propionitrile or benzonitrile as the only source of carbon and nitrogen. Resting cells of this bacterium hydrolysed a number of aliphatic and aromatic mono- and di-nitriles. Rates of hydrolysis and substrate specificities depended on growth substrates: resting cells of the bacterium, grown on either propionitrile or benzonitrile, selectively converted fumaronitrile into 3-cyanoacrylic acid, while benzonitrile-grown cells were very effective in selective conversion of 1,3-dicyanobenzene into 3-cyanobenzoic acid. Based on these findings, a method was developed for the preparation of 3-cyanoacrylic acid and 3-cyanobenzoic acid in high yields.

Bacteria in organic synthesis: Selective conversion of 1, 3-dicyanobenezene into 3-cyanobenzoic acid

Abstract Suspensions of Rhodococcus rhodochrous NCIB 11, 216 catalyse hydrolysis of dinitriles into cyanocarboxylic acids under mild conditions. This bioconversion was used for the highly selective synthesis of 3-cyanobenzoic acid from 1, 3-dicyanobenzene.

Selective synthesis of both isomers of morphine 6-β-d-glucuronide and their analogs

Abstract A stereoselective synthesis of both isomers of the pharmaceutically important morphine 6-β- d -glucuronide (M6G) and its analogs was developed. The method is based on the use of ZnBr2 for the key coupling reaction. It was shown that the α/β stereoselectivity of the reaction can be directed and controlled by the amount of ZnBr2. This paper describes the synthesis, analysis and characterization of the α-isomer of M6G, useful as a reference marker for testing purity and stability of the morphine 6-β- d -glucuronide (M6G).

A convenient method for enzymatic benzyl-alkyl transesterification under mild neutral conditions

Abstract Lipases from Candida cylindracea and from Pseudomonas fluorescens efficiently catalyse the benzyl to alkyl transesterification in organic solvents under mild conditions in nearly quantitative yields.

Stereo- and regioselectivity in asymmetric synthesis of α-amino substituted benzocyclic compounds

Abstract The enantiomerically pure chiral benzocyclic amines 6 – 8 were obtained by asymmetric transamination of the corresponding prochiral ketones 9a – c . The method involves: (a) formation of chiral imines 10a – c from the prochiral ketones 9a – c and the inexpensive chiral auxiliary ( R )- or ( S )-phenylethylamine (PEA); (b) asymmetrically induced reduction of these imines to the diastereomeric amines 11a – c and 12a – c ; (c) catalytic hydrogenation to remove the benzylic fragment of the chiral PEA auxiliary. The stereoselectivity of the imine reduction, as well as the regioselectivity of the catalytic hydrogenation, are strongly dependent on the size of the saturated ring condensed with the benzene ring. This approach was used to develop a convenient, high yielding, and stereoselective route to several practically important optically active α-amino substituted benzocyclic compounds.

Lipase catalysed hydrolysis of γ-substituted α-aminobutyrolactones

Abstract Porcine pancreatic lipase catalyses stereospecific hydrolysis of N-protected α-aminobutyrolactones and of their γ-substituted derivatives. This provides the first example of lipase catalysed synthesis of chiral disubstituted γ—lactones.