SYNTHESIS OF A CLOSE ANALOG OF THE REPEATING UNIT OF THE ANTIFREEZE GLYCOPROTEINS OF POLAR FISH

Article abstract of DOI:10.1016/0008-6215(88)85096-1

The protected glycopeptide N-(benzyloxycarbonyl)-L-alanyl-3)-O-(2,4,6-tri-O-benzyl-α-D-galactopyranosyl)-(1->3)>-L-threonyl-L-alanine 2,2,2-trichloroethyl ester (21) was made by coupling the respective disaccharide and tripeptide blocks.The disaccharide block was generated by coupling tetra-O-benzoyl-α-D-galactopyranosyl bromide to allyl 2,4,6-tri-O-benzyl-α-D-galactopyranoside and converting the product into O-(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)-(1->3)-2,4,6-tri-O-benzyl-α-D-galactopyranosyl chloride (6) 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-α-D-galactopyranoside (10) 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 α-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-α-D-galactopyranosyl chloride, and of the tripeptide by 6, proceeded with excellent α-stereoselectivity.From the disaccharide tripeptide 21, the carboxyl-deprotected and fully deproptected derivatives were prepared.