Synthesis of macromolecular systems via lipase catalyzed biocatalytic reactions: applications and future perspectives

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz. ‘‘lipases’’ in synthetic transformations, the resolution of pharmaceutically important small molecules including polyphenols, amides, nucleosides and their precursors, the development of macromolecular systems (and their applications as drug/gene carriers), flame retardants, polymeric antioxidants and nanocrystalline solar cells, etc

Design, synthesis and anti-inflammatory evaluation of PEGylated 4-methyl and 4, 8-dimethylcoumarins

Aberrant interaction between the leukocyte and the endothelial cell (EC) resulting from the deregulated expression of cell adhesion molecules (CAMs) on the endothelium results in uncontrolled inflammation leading to various inflammatory disorders. The existing drugs used to modulate the cytokine-induced expression of cell molecules have severe side effects. Therefore, there is an unmet therapeutic need to develop potent and safe drugs to treat inflammatory disorders. In the present study, novel PEGylated and non-PEGylated 4-methyl and 4,8-dimethylcoumarin derivatives were designed, synthesized and, evaluated for ICAM-1 inhibitory activity. The PEGylated coumarins were synthesized in two different ways. In the first approach, diesters of 4-methyl and 4,8-dimethylcoumarin were co-polymerized, separately with poly(ethylene glycol) using Candida antarctica lipase under solventless conditions. In the other approach, 4-methyl and 4,8-dimethylcoumarins were suitably converted to their bromo analogues and were tethered to already synthesized PEGylated polymers. Synthesized derivatives were evaluated for anti-inflammatory activities with respect to their ability to inhibit the TNF-α induced ICAM-1 (intercellular cell adhesion molecule-1) on human endothelial cells. It was found that PEGylated 4-methyl and 4,8-dimethylcoumarin derivatives were more effective than their non-PEGylated analogues to inhibit ICAM-1 expression. The present study opens new vista for PEGylated non-steroidal anti-inflammatory compounds and their further investigations

<i style="">Candida rugosa </i>lipase-mediated enantioselective acetylation studies on (±)-3-arylmethyl-3-hydroxymethyl-2,3-dihydro-1-benzopyran-4(<i>H</i>)-ones

356-365Candida rugosa lipase, catalyzed enantioselective acetylation reactions have been performed on novel (±)-3-arylmethyl-3-hydroxymethyl-2,3-dihydrobenzopyran-4-ones in diisopropyl ether. The Candida rugosa lipase-catalyzed acetylations exhibit the enantiomeric separation of the racemic compounds 5a-g, the enantioselectivity of the reaction has been found to be highly dependent on the structure of the substrate. The enantiomeric excess (ee) values are determined by 1H NMR spectral analysis of their O-acetylmandelic acid esters and highest enantiomeric excess obtained is 79% in case of 5c

Synthetic and biological activity evaluation studies on novel isoxazolidines

2670-2682Enantioselective deacetylation reactions on 5-acetoxymethyl- and 5-acetoxy-3-aryl-2-phenyli soxazolidines using Candida rugosa lipase (CRL) are described.Varying degrees of enantioselectivity have been observed depending on the nature of the 3-aryl group. These compounds have also been evaluated for their anti oxidant and antimycobacterial activities

Synthetic and novel biocatalytic resolution studies on (+/-)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins

Eleven (+/-)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins have been synthesised in two steps starting from the coupling of cinnamic acid/substituted cinnamic acid with appropriate phenols, followed by acetylation in 50-83% overall yields. All hydroxy- and acetoxycoumarins were unambiguously identified on the basis of their spectral data. Candida antarctica lipase-catalysed deacetylation of these racemic acetoxydihydrocoumarins in dioxane occurred with moderate enantioselectivity. This is one of the rare examples of resolution using phenolic ester moiety as a remote handle for chiral recognition by a lipase. (C) 2002 Elsevier Science Ltd. All rights reserved