Hiroyasu Furui

Studies on 1-Deoxynojirimycin-Containing Glycans: Synthesis of Novel Disaccharides Related to Lactose, Lactosamine, and Chitobiose

Abstract Suitably protected 1-deoxynojirimycin (l, 5-dideoxy-l, 5-imino-D-glucitol; DNJ) and its 2-acetamido derivative, i.e., 2, 3, 6-tri-O-benzyl-.N-benzyloxycarbonyl-l, 5-dideoxy-1, 5-imino-D-glucitol (6) and 2-acetamido-3, 6-di-O-benzyl-N-benzyloxycarbonyl-1, 2, 5-trideoxy-l, 5-imino-D-glucitol (14) were each coupled with methyl 2, 3, 4, 6-tetra-O-acetyl-1-thio-β-D-galactopyranoside (15) in the presence of dimethyl(methylthio)-sulfonium triflate (DMTST) as a promoter, to give 16 and 18, which were converted to the novel disaccharides (20, 21) related to lactose and lactosamine. Coupling of 14with methyl 3, 4, 6-tri-O-acetyl-2-deoxy-2-phthalimido-l-thio-β-D-glucopyranoside (22) gave achitobiose analog (25). O-(β-D-Galactopyranosyl)-(l→3)-DNJ derivatives (38, 39) and O-(β-D-glucopyranosyl)-(l→3)-DNJ (45) were also synthesized. Conformational analysis of a variety of DNJ derivatives, based on the 1H NMR data, is also discussed.

Systematic synthesis of N-methyl-1-deoxynojirimycin-containing, Lex, Lea, sialyl-Lex and sialyl-Lea epitopes recognized by selectins☆

A systematic synthesis of the N-methyl-1-deoxynojirimycin-containing oligosaccharides related to the Lewis x, Lewis a, sialyl-Lewis x and sialyl-Lewis a antigens has been achieved. The couplings of the suitably protected 1-deoxynojirimycin derivative 10 with methyl-1-thioglycosides (glycosyl donors) of L-fucose (11), D-galactose (15) and alpha-sialyl-(2-->3)-D-galactose (27) were carried out by using dimethyl(methylthio)sulfonium triflate (DMTST) or N-iodosuccinimide/trifluoromethanesulfonic acid (NIS/TfOH) as the glycosyl promoter. The resulting di- and tri-saccharides were each converted, by further cross glycosylations with 11, 15 or 27, to the desired tri- and tetra-saccharides 3-6 that inhibit the recognition between sialyl-Lewis x and selectins, a family of leukocyte cell adhesion molecules.

Synthetic Studies on Sialoglycoconjugates 45: Synthesis of 1-Deoxynojirimycin-Containing Oligosaccharides Related to the Cancer-Associated Sialyl-Lewis a Antigen Recognized by Lec-Cams (Selectins)

Abstract Sialyl-Lewis a (sLea), mainly expressed on cancer cells of the digestive organs,2 has been known as an important cancer-associated carbohydrate antigen.3 Very recently, it has been demonstrated4–9 that the (sLea) antigen is one of the possible ligands recognized by selectins, a family of lectin-type cell adhesion molecules (LEC-CAMS). These findings suggest that the (sLea) antigen may be involved in the process of hematogeneous metastasis of cancer cells. 1-Deoxynojirimycin (DNJ) and related compounds have been shown10 not only to be potent inhibitors of a-glycosidases and glycoprotein-processing enzymes, but also to be of potential clinical value as antidiabetic, antineoplastic and anti-HIV agents. In a preceding paper we reported the synthesis of DNJ-containing sialyl-Lewis x antigen which has been identified as a major carbohydrate ligand for leukocyte adhesion on vascular endothelium mediated by selectins. The present paper describes the first synthesis of l-deoxynojirimycin- containing cance...

Synthetic Studies on Sialoglycoconjugates 53: Synthesis of Novel N-Methyl-1-Deoxynojirimycincontaining Sialo-Oligosaccharides Related to Ganglioside GM3 Active as a Biosignal Mediator

Abstract O-(6-O-Benzoyl-β-d-galactopyranosyl)-(1→4)- and O-(2, 3, 4-tri-O-acetyl-β-d-galactopyranosyl)-(1→4)-2, 3, 6-tri-O-benzyl-N-benzyloxycarbonyl-1, 5-dideoxy-1, 5-imino-d-glucitols (4 and 12) were each coupled with methyl (methyl 5-acetamido-4, 7, 8, 9-tetra-O-acetyl-3, 5-dideoxy-2-thio-d-glycero-d-galacto-2-nonulopyranosid)onate (5) in acetonitrile medium in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) or N-iodosuccinimide/trifluoromethanesulfonic acid to give the corresponding α-sialyl-(2 → 3)- and α-sialyl-(2 → 6)-glycosides (6 and 13α), which were converted to novel ganglioside GM3-related trisaccharides (9 and 15) containing N-methyl-1-deoxynojirimycin.

Studies on Selectin Binding Inhibitors: Synthesis of Sialyl-Lewis X and Sialyl-Lewis A Epitope Analogs Containing 2-Acetamido Derivative of N-Methyl-1-Deoxynojirimycin1

Abstract Synthesis of sialyl-Lewis x (15) and sialyl-Lewis a (17) epitope analogs containing the 2-acetamido derivative of N-methyl-1-deoxynojirimycin has been achieved. A suitably protected 2-acetamido- 1-deoxynojirimycin derivative 5, prepared from 1-deoxynojirimycin via the epoxide intermediate 3, was successively coupled with methyl- 1-thioglycosides of L-fucose (6) and β-sialyl-(2→3)-D-galactose (9). The resulting tetrasaccharides (10 and 13) were each converted, by reductive N-methylation and deprotection, into the desired epitope analogs.

SYNTHESIS OF SIALYL- AND SULFO-Lex/Lea ANALOGS CONTAINING N-ALKYL-1-DEOXYNOJIRIMYCIN AS POTENTIAL SELECTIN BLOCKERS[1]

A series of novel sialyl- and sulfo-Lex/Lea oligosaccharides containing N-alkyl-1-deoxynojirimycin as potential selectin blockers have systematically been synthesized via the suitably protected intermediates containing N-benzyloxycarbonyl-1-deoxynojirimycin. Some of the synthetic oligosaccharides strongly inhibited the adhesion of HL60 cells to IL-1β-stimulated HUVECs.

Synthetic Studies on Sialoglycoconjugates 49: Novel Disaccharides and Lactams Composed of Sialic Acid and 1-Deoxynojirimycin-Potential for Biomedical Application

Abstract Sialic acid-containing glycoconjugates participate in a variety of biological functions on cell surfaces, not only serving as receptors for hormones, viruses and bacteria but also as mediators in cell growth, differentiation, adhesion, oncogenesis and so on. For example, influenza virus1,2 and tripanosoma cruzi 3,4 recognize sialic acid in the time of infection to animal cells. Recently, the sialyl-Lex (sLex) and sialyl-Lea (sLea) carbohydrate epitopes have been highlighted as the ligands for selectins, a family of cell adhesion molecules involved in leukocyte traffic5,6 and tumor metastasis.7 1-Deoxynojirimycin (DNJ) and related compounds are well known8 as the potent inhibitors of a-glycosidases and glycoprotein-processing enzymes. Some of the Nsubstituted DNJ derivatives have been noted as antidiabetic and anti-HIV agents.