The synthesis, and study of the β-elimination reaction, of di- and tri-peptides having a 3-O(2-acetamido-3,4,6-trio-O-acetyl-2-deoxy-β-D-glucopyranosyl)-L-serine residue

Abstract 2-Acetamido-3,4,6-tri- O -acetyl-2-deoxy-α- D -glucopyra-nosyl chloride was condensed with the N -(benzyloxycarbonyl) derivatives of, respectively, L -seryl-glycine ethyl, L -seryl- L -alanine methyl, L -seryl- L -phenylalanine methyl, and L -seryl- L -aspartic dibenzyl esters to give (3- O -Gl cp NAc-CbzN- L -Ser)-GlyOEt ( 8 ), (3- O -Gl cp NAc-CbzN- L -Ser)- L -AlaOMe ( 9 ), (3- O -Gl cp NAc-CbzN- L -Ser)- L -PheOMe ( 10 ), and (3- O -Gl cp NAc-CbzN- L -Ser)- L -Asp(diOBzl) ( 11 ), respectively; O -(2-acetamido-3,4,6-tri- O -acetyl-β- D -glucopyranosy-l)- N -(benzyloxycarbonyl)- L -serine methyl ester was deblocked by treatment with hydrobromic acid in glacial acetic acid, followed by triethylamine, to give a glycoamino acid that was condensed with the N -(benzyloxycarbonyl) derivatives of the p -nitrophenyl ester of glycine, L -alanine, and L -proline, respectively, to give CbzNGly-(3- O )-Gl cp NAc- L- SerOMe) ( 17 ), CbzN- L -Ala-(3- O -Gl cp NAc- L -SerOMe), and CbzN- L -Pro-(3- O -Gl cp NAc- L -SerOMe), respectively. Similarly, the glycopeptide resulting from 8 was condensed with the activated esters of glycine, L -alanine, L -phenylalanine, L -proline, and L -serine, respectively, to give CbzNGly-(3- O Gl cp NAc- L -Ser)-GlyOEt, CbzN- L -Ala-(3- O -Gl cp NAc- L -Ser)-GlyOEt, CbzN- L -Phe-(3- O -Gl cp NAc- L -Ser)-GlyOEt, and CbzN- L -Ser-(3- O -Gl cp NAc- L -Ser)-GlyOEt, respectively; that from 9 , with the p -nitrophenyl esters of glycine 1 , L -alanine, L -phenylalanine, L -proline, and L -leucine, respectively, to give CbzNGly-(3- O -Gl cp NAc- L -Ser)- L -AlaOMe, CbzN- L -Ala(3- O -Gl cp NAc- L -Ser)- L -AlaOMe, CbzN- L -Phe-(3- O -Gl cp NAc- L -Ser)- L] -AlaOMe, CbzN- L -Pro-(3- O -Gl cp NAc- L -Ser)- L -AlaOMe, and CbzN- L -Leu-(3- O -Gl cp NAc- L -Ser)- L -AlaOMe, respectively; that from 10 , with the derivatives of glycine, L -alanine, L -phenylalanine, and L -leucine, respectively, to give CbzNGly-(3- O -Gl cp NAc- L -Ser)- L -PheOMe, CbzN- L -Phe-(3- O -Gl cp NAc- L -Ser)- L -PheOMe, CbzN- L -Phe-(3- O -Gl cp NAc- L -Ser)- L -PheOMe, and CbzN- L -Leu-(3- O -Gl cp NAc- L -Ser)- L -PheOMe, respectively; and that from 11 , with the derivatives of glycine, L -alanine, L -phenylalanine, L -proline, and L -leucine, respectively, to give CbzNGly-(3- O -Gl cp NAc- L -Ser)- L -Asp(diOBzl), CbzN- L -Ala-(3- O -Gl cp NAc- L -Ser)- L -Asp(diOBzl), CbzN- L -Phe-(3- O -Gl cp NAc- L -Ser)- L -Asp(diOBzl), CbzN- L -Pro-(3- O -Gl cp NAc- L -Ser)- L -Asp(diOBzl), and CbzN- L -Leu-(3- O -Gl cp NAc- L -Ser)- L -Asp-(diOBzl), respectively. O -(2-Acetamido-3,4,5-tri- O -acetyl-2-deoxy-β- D -gluco-pyranosyl)- N -(benzyloxycarbonyl)- L -asparaginylglycyl- L -serine methyl ester ( 20 ) was synthesized by treating the free amine of 17 with the p -nitrophenyl ester of N -(benzyloxycarbonyl)- L -asparagine. 2-Acetamido-3,4,6-tri- O -acetyl-1- N -[ N -(benzyloxycarbo-nyl)- L -aspart-1-oyl-(glycyl- L -serine methyl ester)-4-oyl]-2-deoxy-β- D -glucopyranosylamine ( 41 ) was synthesized by the condensation of 2-acetamido-3,4,6-tri- O -acetyl-1- N -[ N -(benzyloxycarbo-nyl)- L -aspart-4-oyl]-2-deoxy-β- D -glucopyranosylamine with glycyl- L -serine methyl ester. Attempts to transfer the 2-acetamido-3,4,6-tri- O -acetyl-2-deoxy- D -glucopyranosyl group from the hydroxyl group of L -serine in 20 to the amido group of L -asparagine, to give 41 , were unsuccessful. The β-elimination of some of the glycodi- and glycotri-peptides was studied.