Osamu Tsuruta

UDP-N-acetyl-5-thio-galactosamine is a substrate of lactose synthase

Abstract Uridine 5′-(N-acetyl-5-thio-galactosaminyl diphosphate) (UDP-5SGalNAc) was synthesized from an N-acetylgalactosamine derivative via ring opening-recyclization approach. UDP-5SGalNAc was active as a donor substrate for lactose synthase, the complex of galactosyltransferase and lactalbumin, giving the disaccharide mimic (5SGalNAcβ[1→4]GlcNAc) which has a sulfur in the ring of the non-reducing sugar. The initial rate of the formation of the disaccharide mimic was 0.23 % that for the natural disaccharide (GalNAcβ[1→4]GlcNAc).

A facile synthesis of 5-thio-l-fucose and 5-thio-d-arabinose from d-arabinose

Abstract 5-Thio- l -fucopyranose tetraacetate was synthesized in 11 steps from 5-O- trityl- d -arabino-furanose or d -arabinose diethyl dithioacetal by one-carbon elongation at C-5. Highly diastereo-selective addition of MeLi in ether to a 1,2-O- isopropylidene -β- d -arabino- pentodialdo-1,4-furanose derivative was achieved to give the corresponding 6-deoxy-β- d -altrofuranose isomer in good yield. A sulfur atom was introduced at C-5 of 6-deoxy- d -altrofuranose derivatives via substitution of a 5-tosylate with KSAc in HMPA with inversion of configuration, giving 5-thio- l -fucopyranose. A 3-O- substituted- l -fucose derivative was also prepared from 6-deoxy-β- d -altrofuranose derivatives. 5-Thio- d -arabinopyranose tetraacetate, the 5-demethyl analog of 5-thio- l -fucose, was also synthesized from 5-O- trityl- d -arabinofuranose in 5 steps. 5-Thio- d -arabinose showed weak inhibitory activity against α- l -fucosidase from bovine kidney ( K i = 0.77 mM ).

Syntheses of two trimannose analogs each containing C-mannosyl or 5-thio-C-mannosyl residue: their affinities to concanavalin A

C-Mannosyl residue-containing trimannose ManC alpha(1,6)[Man alpha(1,3)Man] (2) and 5-thio-C mannosyl residue-containing trimannose 5SManC alpha(1,6)[Man alpha(1,3)Man] (3) were synthesized via a glycosyl radical addition to enone derivative of mannose (6). Dissociation constants for the binding of these trisaccharides to concanavalin A (ConA) were determined by a fluorescence anisotropy inhibition assay: Kd = 198 and 31 microM, respectively. The unexpectedly large Kd value for the compound 2 compared with the compound 3 and the natural trimannose 1 demonstrates a characteristic of C-glycoside.

Synthesis of 5-thio-l-fucose-containing blood group antigens H-type 2 and Lewis X (Lex)

Abstract Two blood group antigens, H-type 2 and Lewis X trisaccharides containing 5-thio- l -fucose instead of l -fucose, were synthesized. 2-Azido-2-deoxy-lactose derivative 11 was used as the common disaccharide intermediate. 5-Thio- l -fucosylation of the 2′-OH and 3-OH groups of 1,6-anhydro-2-azido-2-deoxy-lactose derivative by a trichloroacetimidate method gave α-linked trisaccharides stereoselectively.

p-Nitrophenyl 1,5-dithio-α-l-fucopyranoside: a novel sulfur based fucosidase inhibitor

Abstract Five 5-thio-α- l -fucopyranosyl derivatives were prepared and examined as inhibitors of the α- l -fucosidase from bovine epididymis. The inhibitory activities of the fucosides strongly depend on the hydrophobicity of the aglycon. The best inhibition ( K i = 3.3 μM) was obtained with p -nitrophenyl 1,5-dithio-α- l -fucopyranoside.

Affinity of 5-thio-L-fucose-containing lewis X (LeX) trisaccharide analogs to anti-LeX monoclonal antibody

5-Thiofucose-containing LeX trisaccharide analogs Gal beta(1,4)[5SFuc alpha(1,3)]GlcNAc-OMe (2) and Gal beta(1,4)[5SFuc beta(1,3)]GlcNAc-OMe (4) were synthesized via 5-thiofucosylation of methyl 2-azido-lactoside derivative 6 by the trichloroacetimidate method. Inhibitory activity of these analogs for the binding of LeX to anti-Lex antibody was evaluated by enzyme immunoassay, indicating that anti-LeX strictly recognizes alpha-configuration of the fucose moiety and its binding pocket includes no advantageous region, such as hydrophobic area, for recognizing the ring sulfur atom of 5-thiofucosyl LeX analog 2.