O-Glycosyl amino acids

Although Ag0Tf/K2C03 had proved to be a suitable promoter in connection with the synthesis of the O-glycosylated amino acid building blocks related to TF antigen... 

The solution methods require orthogonal protection of the C- and N-termini of the N- or O-glycosyl amino acid or peptide as well as of the glycan throughout the synthesis. Furthermore, protection of the C- and N-termini should both be of the temporary type, which can be removed under mild selective conditions to have the peptide elongated in either direction. 

The protected O-glycosyl amino acid ester or O-glycosyl peptide ester (1 mmol) is stirred in morpholine (10 mL) or morpholine-dichloromethane (1 1) for 30 min. After addition of dichloromethane (100 mL), the solution is washed with diluted aqueous acid (citric acid or HC1 pH 4, 50 mL) and with water (4 x 50 mL), dried with NajSO, and concentrated in vacuo. The crude product is dissolved in 2-5 mL of ethyl acetate. During chromatography on silica gel (50 g) with petrolum ether ethyl-acetate (2 1), W-(9-fluorenylmethyl)morpho-line is eluted. Subsequently, the deblocked amino acid or peptide ester is eluted with methanol. 0-(2,3,4-Tri-0-benzoyl-(3-D- xylopyranosyl)-L-serine benzyl ester 14 yield, 0.63 g (98%) mp 55°C [a]D —41.4 (c 0.5, CH3OH). IV-(L-Asparaginyl-L-leucyl-)-0-(2,3,4,-0-benzoyl-(3-D-xylopyranosyl)-L-serine benzyl ester 17 yield, 0.85 g (98%) amorphous [a]D —42.3° (c 0.5 CH3OH). 

Key Words Glycosylation N- and O-glycosylated amino acids solid-phase synthesis ... 

The most widely used approaches in the synthesis of the O-glycosylated amino acids, Koenigs-Knorr, activation of anomeric acetate, trichloroacetim-idate, and thioglycosides will be explained in detail. 

Remarkable advances have been made in the synthesis of N- and O-glycosylated amino acids that, in addition to the 5-fattyacyl-cysteine, are the most sensitive derivatives to the conditions of peptide synthesis. The fine tuning of both carbohydrate and peptide chemistry as well as the use of enzymatic methods are required for the synthesis of glycopeptides. " Similarly soft chemistry has to be applied in the case of S-acylated peptides, whereas fat-tyacylation at amino groups raises no additional difficulties.The state of the art in the field of glyco- and lipopeptide synthesis is discussed in details in Vol. E22b, Sections 6.3 and 6.4, respectively. 

Fig. 5. Schematic diagram of the presumed arrangement of the amino acid sequence for the 5-opioid receptor, showing seven putative transmembrane segments three intracellular loops, A three extracellular loops, B the extracellular N-terrninus and the intracellular C-terrninus, where (0) represents amino acid residues common to ] -, 5-, and K-receptors ( ), amino acid residues common to all three opioid receptors and other neuropeptide receptors and (O), other amino acids. Branches on the N-terruinal region indicate possible glycosylation sites, whereas P symbols in the C-terminal region indicate...

The tetra-O-benzylated A-Fmoc derivative of 165 was then incorporated by solid-phase synthesis into a helix-forming glycoheptadecapeptide, Ac-Tyr-Lys-Ala-Ala-Ala-Ala-Lys-Ala-Ala-Cgaa((3-D-Gal-C-)-Ala-Lys-Ala-Ala-Ala-Ala-Lys-NH2 (Cgaa= C-glycosylated amino acid)J128l... 

The linear assembly of glycosylated amino acids in particular usually provides well-defined products following this approach, the required carbohydrate structure is attached to an amino acid residue, typically serine and threonine for O-linked glycopeptides and asparagine for N-linked glycopeptides (Fig. I).16... 

SCHEME 1S.9 1,2 -cw-O-Linked glycosylated amino acids are predominantly prepared using nonparticipating O-benzyl or azido groups at C-2 of the glycosyl donor. 

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