Application of lipase-catalyzed regioselective esterification in the preparation of digitonin derivatives.
The oligosaccharide chain of the monodesmosidic haemolytic saponin digitonin (1) undergoes an efficient and regioselective acylation in organic solvent by use of Novozym 435 (lipase B from Candida antarctica supported on acrylic resin) in the presence of an activated ester. With vinyl acetate, acetylation occurs at C-6 OH of glucose(II) and C-4 OH of xylose to afford the previously unreported diacetyl derivative 2 and the monoacetyl derivatives 3 and 4. With vinyl laurate only the monolauryl derivative 5 is formed. The structures of these acylated digitonins have been established using modern 2D NMR techniques, which allowed complete assignments of all proton resonances. The hemolytic activity of derivatives 2-5 is significantly reduced compared to that of digitonin.
Danieli
B
B
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Centro CNR di Studio per le Sostanze Organiche Naturali, via Venezian 21, 20133 Milano, Italy. danieli@icil64.cilea.it
Luisetti
M
M
Steurer
S
S
Michelitsch
A
A
Likussar
W
W
Riva
S
S
Reiner
J
J
Schubert-Zsilavecz
M
M
D000818:Animals; D002175:Candida / Q000201:enzymology; D002240:Carbohydrate Sequence; D002417:Cattle; D004072:Digitonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D004952:Esters; D006461:Hemolysis; D066298:In Vitro Techniques; D008049:Lipase; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data
D004952:Esters; D008049:Lipase; D004072:Digitonin