Angela Patti

Resolution of racemic flurbiprofen by lipase-mediated esterification in organic solvent

Abstract Resolution of rac-flurbiprofen, 2-fluoro-α-methyl-[1,1′-biphenyl]-4-acetic acid (1), by biocatalytic methodologies has been studied. Enzymatic hydrolysis of rac-flurbiprofen methyl ester (2) in aqueous-organic medium gave poor results. Transesterification of the same ester mediated by immobilized lipase from Candida antarctica (Novozym® 435) in organic solvent proceeded with good enantiomeric excess but the isolation of the product required chromatographic separation and therefore was unsuitable for large scale preparation. Direct esterification of 1 with methanol in acetonitrile promoted by Novozym® 435 proved to be the best method since it gave, via a twofold kinetic resolution, S-flurbiprofen with excellent enantiomeric excess. The R-flurbiprofen methyl ester formed in the reaction can be converted into the starting rac-flurbiprofen by alkaline hydrolysis or, alternatively, into R-flurbiprofen by hydrolysis with acid.

Use of Mucor miehei lipase in the preparation of long chain 3-O-acylcatechins

Long chain 3-O-acylcatechins were prepared in high yield by alcoholysis with n-butanol of the corresponding pentaacylderivatives in the presence of lipase from Mucor miehei (immobilised, Lipozyme® IM). In an alternative procedure, the mixed ester, tetraacetyl-3-O-acylcatechin, was synthesised and used as substrate for the same alcoholysis process that proceeds with higher reaction rate. The obtained 3-O-acyl derivatives are more lipophilic than the parent catechin and thus suitable for a possible application of their antioxidative properties in hydrophobic matrices.

Screening of chiral ferrocenyl amino alcohols as ligands for ruthenium-catalysed transfer hydrogenation of ketones

A variety of ferrocenyl amino alcohols possessing central chirality have been screened as ligands for ruthenium(II)-catalysed transfer hydrogenation of acetophenone using 2-propanol in the presence of KOH as the hydrogen source. Enantiomerically enriched 1-phenylethanol was obtained in high yield and 70% e.e. using ligand 9. This ligand was employed in the asymmetric reduction of different arylalkyl ketones and the corresponding alcohols were obtained in up to 80% e.e. A comparison of the catalytic properties of ferrocenyl amino alcohols and their phenyl analogues is discussed briefly.

Lipase-mediated resolution of 2-hydroxymethyl-1-iodoferrocene: synthesis of ferrocenes and biferrocenes with planar chirality

Abstract Racemic 2-hydroxymethyl-1-iodoferrocene (±)- 1 was subjected to esterification in the presence of lipase from Candida antarctica (Novozym ® 435) to afford (1 S ,2 S )-2-acetoxymethyl-1-iodoferrocene (−)- 2 having 89% ee and unreacted (1 R ,2 R )-2-hydroxymethyl-1-iodoferrocene (+)- 1 in enantiopure form. A single enantiomer of 2-hydroxymethyl-1-iodoferrocene gave easy access to new ferrocenes and biferrocenes possessing only planar chirality.

Application of lipase catalysis in organic solvents for selective protection–deprotection of bioactive compounds

Abstract Lipases are useful catalysts to realise in non-conventional medium esterifications and alcoholysis of polyhydroxylated compounds with high level of regioselectivity. This paper describes some examples of regioprotection–deprotection of flavonoids and conduritols, realised in our laboratory, using Pseudomonas cepacia, Mucor miehei and Candida cylindracea (C. rugosa) lipases.

AN EFFICIENT ENZYMATIC PREPARATION OF (+)- AND (-)-CONDURITOL E, A CYCLITOL WITH C2 SYMMETRY

Abstract Lypozyme® IM (immobilised lipase from Mucor miehei) catalyses the enantiomeric alcoholysis of tetraacetylconduritol E (±)−2 to give enantiopure (1R,2R,3R,4R)-tetrahydroxycyclohex-5-ene, (−)−1, and the unreacted ester (1S,2S,3s,4S)-tetraacetyloxycyclohex-5-ene, (+)−2. The latter was transformed by basic hydrolysis into (+)−1 in high yield and 95% ee. Selective amination of partial ester (−)−3, obtained by short alcoholysis of (±)−2, furnished the previously unreported conduramine F-4, (−)−4.

Synthesis of α,β-disubstituted ferrocenes via a ferrocenylepoxide intermediate. Preparation and catalytic activity of a new chiral ferrocenyloxazoline

Abstract A short synthesis of the chiral oxazoline 10 (>95% e.e.) in six steps from chloroacetylferrocene is described. The ligand can be used successfully in an asymmetric Pd(0)-catalyzed allylic alkylation reaction.

Lipase-assisted preparation of enantiopure ferrocenyl sulfides possessing planar chirality and their use in the synthesis of chiral sulfoxides

Abstract Racemic 2-hydroxymethyl-1-phenylthioferrocene 5 and 2-hydroxymethyl-1-tert-butylthioferrocene 6 were subjected to kinetic resolution via acetylation catalysed by lipase from Candida antarctica (Novozym® 435) or Mucor miehei (Lipozyme® IM). The obtained enantiopure thioethers underwent chemical oxygenation at the sulfur atom to give the corresponding ferrocenyl sulfoxides with settled central/planar chirality.

Enantiopure 1-hydroxymethyl-2-dimethylaminomethylferrocene as efficient catalyst in the enantioselective addition of diethylzinc to aldehydes

Abstract A ferocenyl amino atodml possessing only planar chirality has been employed as a catalyst in the enantioselective alkylation of aldehydes with Et 2 Zn. Seven chiral secondary alcohols in 64∼83% e.e. have been prepared.

LIPASE-MEDIATED RESOLUTION OF RACEMIC 2-HYDROXYMETHYL-1-METHYLTHIOFERROCENE

Abstract Both enantiomers of 2-hydroxymethyl-1-methylthioferrocene have been obtained with high optical purity by lipase-catalysed resolution of the racemate.