Synthesis of a close analog of the repeating unit of the antifreeze glycoproteins of polar fish.
The protected glycopeptide N-(benzyloxycarbonyl)-L-alanyl-[O-(2,3,4,6-tetra-O-benzoyl-beta-D- galactopyranosyl)-(1----3)-O-(2,4,6-tri-O-benzyl-alpha-D-galactopyranosy l)- (1----3)]-L-threonyl-L-alanine 2,2,2-trichloroethyl ester was made by coupling the respective disaccharide and tripeptide blocks. The disaccharide block was generated by coupling tetra-O-benzoyl-alpha-D-galactopyranosyl bromide to allyl 2,4,6-tri-O-benzyl-alpha-D-galactopyranoside and converting the product into O-(2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl)-(1----3)-2,4,6-tri-O -benzyl - alpha-D-galactopyranosyl chloride via the 1-propenyl glycoside and the free (1-OH) sugar. Alternatively, the 1-propenyl intermediate was obtained directly by using 1-propenyl 2,4,6-tri-O-benzyl-alpha-D-galactopyranoside as the acceptor in the initial coupling reaction. An efficient 3-step synthesis of 10 was accomplished by the dibutyltin oxide-assisted, selective crotylation of allyl alpha-D-galactopyranoside at O-3, followed by benzylation and treatment of the product with potassium tert-butoxide. The N-benzyloxycarbonyl (Z) and N-tert-butoxycarbonyl (Boc) 2,2,2-trichloroethyl esters of Thr-Ala and Ala-Thr-Ala were formed by sequential coupling. The silver triflate-promoted glycosylation of the Z-protected dipeptide and tripeptide by 2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl chloride, and of the tripeptide by 6, proceeded with excellent alpha-stereoselectivity. From the disaccharide tripeptide 21, the carboxyl-deprotected and fully deprotected derivatives were prepared.
Anisuzzaman
A K
AK
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.
Anderson
L
L
Navia
J L
JL
D000818:Animals; D021301:Antifreeze Proteins; D004187:Disaccharides / Q000138:chemical synthesis; D005399:Fishes; D005615:Freezing; D006020:Glycopeptides / Q000138:chemical synthesis*; D006023:Glycoproteins / Q000138:chemical synthesis*; D006031:Glycosylation; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation
D021301:Antifreeze Proteins; D004187:Disaccharides; D006020:Glycopeptides; D006023:Glycoproteins; D007202:Indicators and Reagents