Giovanni Nicolosi

Antimicrobial and Anti-Lipase Activity of Quercetin and its C2-C16 3-O-Acyl-Esters

Neither quercetin (Q), nor 3-O-acylquercetines, up to 100 microg/mL, had any significant activity on selected gram-positive strains (Staphylococcus aureus, Bacillus subtilis, Listeria ivanovi, Listeria monocytogenes, Listeria serligeri), gram-negative strains (Escherichia coli, Shigella flexneri, Shigella sonnei, Salmonella enteritidis, Salmonella tiphymurium) and yeasts (Candida albicans and Candida glabrata). In addition, we confirmed the known anti-HIV activity of Q (80% inhibition at 40 microM), which might depend on the free hydroxyl in the C-3 position, as suggested by the lack of activity of the 3-O-acylquercetines. Finally, we described an interesting inhibitory activity on Candida rugosa lipase by Q (IC(16)=10(-4) M) and its esters (3-O-acylquercetines) which, in vivo, could play an important role against lipase producing microorganisms. In particular, 3-O-acyl-quercetines, being more active (IC(16)=10(-4)-10(-6) M) and more lipophilic, could be more effective than Q when applied to the skin or mucosae, and deserve to be studied further.

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.

Chloroperoxidase from Caldariomyces fumago is active in the presence of an ionic liquid as co-solvent

Chloroperoxidase from Caldariomyces fumago catalyses the oxidation of 1,2-dihydronaphthalene to (1R,2R)-(+)-dihydroxytetrahydronaphthalene in homogenous citrate buffer/ionic liquid mixtures, using t-butyl hydroperoxide as O<>2<> donor. It tolerates up to 30 (v/v) 1,3-dimethylimidazolium methylsulfate or 1-butyl-3-methylimidazolium methylsulfate. The enzyme activity in these ionic liquid co-solvent systems is retained for 24 h, but it falls to 3 h using non-ionic organic solvents such as t-BuOH or acetone.

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.

Chemo-enzymatic preparation of resveratrol derivatives

Abstract Regioselective derivatisation of resveratrol (1) at positions 3, 5 or 4′ was achieved by a chemo-enzymatic procedure based on standard chemical reactions and esterification or alcoholysis in organic solvents catalysed by the commercially available Pseudomonas cepacia (PcL) and Candida antarctica (CaL) lipases.

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.

Structure and conformation of new diterpenes based on the dolabellane skeleton from a Dictyota species

Abstract From the brown alga Dictyota sp. we have isolated three new diterpenes (2,3 and 6) of the dolabellane family. Their structures and conformations have been assigned on the basis of spectral studies, including proton difference decoupling and nuclear Overhauser enhancement difference spectroscopy, and chemical correlation.

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.

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.