New effective synthesis of (N-acetyl- and N-stearoyl-2-amino-2-deoxy-beta-D-glucopyranosyl)-(1 -> 4)-muramoyl-L-2-aminobutanoyl-D-isoglutamine, analogs of GMDP with immunopotentiating activity

摘要

Ethyl 3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (5), prepared by benzylation of ethyl 2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (4), was transformed by reaction with bromine into 3,4,6-tri-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl bromide (6). Thioglycoside 5 in the presence of methyl triflate and glycosylbromide 6 in the presence of silver triflate were used as glycosyl donors for condensation with benzyl 2-acetamido-3-O-allyl-6-O-benzyl-2-deoxy-alpha-D-glucopyranoside (7), to give benzyl 2-acetamido-3-O-allyl-6-O-benzyl-4-O-(3, 4,6-tri-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-2-deoxy-alph a-D-glucopyranoside (8). Its reductive dephthaloylation with NaBH4/AcOH afforded benzyl 2-acetamido-3-O-allyl-4-O-(2-amino-3,4,6-tri-O-benzyl-2-deoxy-beta-D-gluco pyranosyl)-6-O-benzyl-2-deoxy-alpha-D-glucopyranoside (11). Compound 11 was N-acylated to give benzyl 2-acetamido-4-O-(2-acylamino-3,4,6-tri-O-benzyl-2-deoxy-beta-D-glucopyrano syl)-3-O-allyl-6-O-benzyl-2-deoxy-alpha-D-glucopyranosides (12a) or (12b). These compounds were converted into corresponding benzyl 2-acetamido-4-O-(2-acylamino-3,4,6-tri-O-benzyl-2-deoxy-beta-D-glucopyrano syl)-6-O-benzyl-3-O-carboxymethyl-2-deoxy-alpha-D-glucopyranosides which, by condensation with H-L-Abu-D-isoGln(OBzl) followed by hydrogenolysis of protective benzyl groups, furnished glycopeptides 16a and 16b. Intramolecular O-->N migration of the allyl protecting group followed by its reduction to the propyl residue by reaction of compound 8 with hydrazine or hydrazinium acetate, to give benzyl 2-acetamido-4-O-(3,4,6-tri-O-benzyl-2-deoxy-2-propylamino-beta-D-glucopyra nosyl)-6-O-benzyl-2-deoxy-alpha-D-glucopyranoside (9), is also described. [References: 18]