Thermolysin catalyses the synthesis of cyclodextrin esters in DMSO

• Published in: Tetrahedron: asymmetry Vol. 16; no. 3; pp. 615 - 622
• Main Authors: Pedersen, Ninfa Rangel, Kristensen, Janni Brogaard, Bauw, Guy, Ravoo, Bart Jan, Darcy, Raphael, Larsen, Kim Lambertsen, Pedersen, Lars Haastrup
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 07-02-2005
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/j.tetasy.2004.12.009

Heptakis(2-
O-decanoyl)-β-cyclodextrin was synthesised from native β-cyclodextrin and vinyl decanoate in a one-step reaction catalysed by thermolysin in DMSO. The regioselectivity was directed primarily at the C-2 position but depended on the chain length of the acyl donor.
Fatty acid esters of cyclodextrins (CDs) were synthesised in a one-step reaction with native CDs as acyl acceptors and vinyl-activated fatty acid esters as acyl donors. Immobilised preparations of thermolysin, subtilisin, the alkaline protease AL-89 and
Candida antarctica lipase B were investigated for their catalytic properties regarding transesterification in solvents of increasing hydrophilicity. The synthesis of cyclodextrin fatty acid esters was proved to be catalysed enzymatically by thermolysin in DMSO. The obtained products were analysed by TLC and their structures characterised by NMR, MS and FTIR spectroscopy. With vinyl decanoate as acyl donor β-CD was esterified at all seven glucose C-2 positions resulting in heptakis(2-
O-decanoyl)-β-cyclodextrin as the major product. With vinyl butyrate, substitution occurred at all the C-2 and partially at the C-3 or C-6 positions resulting in an average degree of substitution of nine. Between 20% and 25% (w/w) of the acyl donor was converted to esters in 20
h corresponding to an estimated total conversion of the acyl acceptor in the case of maltosyl-β-CD. In the subtilisin and AL-89 catalysed reactions, product formation was simultaneously catalysed non-enzymatically by inorganic buffer salts in aprotic, hydrophilic solvents and with the lipase no products were formed in any of the solvents investigated.