[1,6-Anhydro-N-Acetyl- beta-D-glucosamine in oligosaccharide synthesis: II. synthesis of a spacered Ley tetrasaccharide].

3-Aminopropyl glycoside of 3,2'-di-O-alpha-L-fucosyl-N-acetyllactosamine (Ley tetrasaccharide) was synthesized. The glycosyl donor, 2-O-acetyl-3,4,6-tri-O-benzoyl-alpha-D-galactopyranosyl bromide, was coupled with glycosyl acceptor, 1,6-anhydro-2-acetamido-2-deoxy-beta-D-glucopyranose or its 3-O-acetyl derivative, to give the corresponding N-acetyllactosamine derivatives in 20 and 71% yields, respectively. The glycosyl donor was synthesized from 1,2-di-O-acetyl-3,4,6-tri-O-benzoyl-D-galactopyranose, which was obtained by the treatment of benzobromogalactose with sodium borohydride to yield 1,2-O-benzylidene derivative and subsequent removal of benzylidene group and acetylation. Acidic methanolysis of the disaccharide derivatives resulted in the selective removal of one or both acetyl groups to give the disaccharide acceptor bearing hydroxy groups at C3 of the glucosamine residue and C2 of the galactose residue. The introduction of fucose residues in these positions by the treatment with tetrabenzylfucopyranosyl bromide resulted in a tetrasaccharide derivative, which was converted into 3,2'-di-O-alphha-L-fucopuranosyl- 1,6-anhydro-N-acetyllactosamine peracetate after substitution of acetyl groups for benzoyl and benzyl groups. Opening of the anhydro ring by acetolysis resulted in peracetate, which was then converted into the corresponding oxazoline derivative in two steps. Glycosylation of the oxazoline derivative with 3-trifluoroacetamidopropan-1-ol and removal of O-acetyl and N-trifluoroacetyl protective groups resulted in a free spacered Ley tetrasaccharide.

[1,6-anhydro-N-acetyl-beta-D-glucosamines in synthesis of oligosaccharides. I. Synthesis of 3-acetate and 3-benzoate of 1,6-anhydro-N-acetyl-beta-D-glucosamine through a 4-O-trityl derivative]. / 1,6-angidro-N-atsetil-beta-D-gliukozamin v sinteze oligosakharidov. I. sinteze oligosakharidov. I. Sintez 3-atsetata i 3-benzoata 1,6-angidro-N=atsetil-beta-D-gliukozamina cherz 4-O-tritil'noe proizvodnoe.

3-O-Acetyl and 3-O-benzoyl derivatives of 1,6-anhydro-N-acetyl-beta-D-glucosamine were synthesized via its selective tritylation followed by the 3-O-acylation and removal of the trityl protective group. Tritylium trifluoromethanesulfonate, which can easily be prepared by mixing solutions of triphenylcarbinol and trimethylsilyl trifluoromethanesulfonate in an equimolar ratio, was suggested as a reagent for the effective tritylation of a secondary hydroxyl group.

[Synthesis of disaccharide Neu5Gcalpha(2-6)GalNAcalpha as a spacer glycoside]. / Sintez disakharida Neu5Gcalpha(2-5)GalNAcalpha v vide speiser- glikozida.

The first synthesis of the Neu5Gc analogue of SiaTn disaccharide, which can be detected in breast tumors by immunochemical methods, is reported. The regioselective sialylation of (3-trifluoroacetamidopropyl)-2-azido-2-deoxy-alpha-D-galactopyranoside with peracetate of the methyl ester of N-acetoxyacetylneuraminic acid beta-ethylthioglycoside in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid (or its trimethylsilyl ester) resulted in the derivatives of alpha- and beta-sialyl(2-->6)galactosaminide in 39 and 32% yields, respectively. The catalytic hydrogenolysis of the azido group and subsquent N- and O-acetylation of the alpha-anomer gave the trifluoroacetamidopropyl glycoside peracetate. Removal of the protective groups led to glycoside Neu5Gc alpha(2-->6)GalNAc alpha-O(CH2)3NH2. Using the Neu5Gc derivative with acetoxyacetyl groups at positions O9 and O4 as a donor increases the alpha-selectivity of sialylation to afford the alpha- and beta-anomers in 69 and 8% yields, respectively.

[Synthesis of Neu5Ac(alpha2-->6)[Gal(alpha1-->3)]GalNAcalpha and Neu5Ac(alpha2-->6)[Gal(beta1-->3)]GalNAcalpha trisaccharides as protected trifluoroacetamidopropyl glycosides]. / Sintez trisakharidov Neu5Ac(alpha2-->6)[Gal(alpha1-->3)]GalNAcalpha i Neu5Ac(alpha2-->6)[Gal(beta1-->3)]GalNAcalpha v vide zashchishchennykh triftoratsetamidopropilglikozidov.

Protected sialo-containing trisaccharides, fragments of oligosaccharide chains of mucin glycoproteins, were synthesized. Regioselective sialylation of the primary hydroxyl group of (3-fluoroacetamidopropyl)-2-azido-2-deoxy-3-O-(2,3,4,6-tetra-O-ben zyl)-alpha -D-galactopyranosyl)-alpha-D-galactopyranoside with methyl ester of peracetyl-beta-ethylthioglycoside of N-acetylneuraminic acid in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid (or its trimethylsilyl ester) yielded 39 and 25% of alpha- and beta-sialyl-(2-->6)biosides, respectively. Catalytic hydrogenolysis of the azide and benzyl groups of the alpha-anomer followed by N- and O-acetylation gave target trifluoroacetamidopropyl glycoside, Neu5Ac(alpha 2-->6)[Gal(alpha 1-->3)]GalNAc alpha-OSp, as a peracetate. An analogous coupling of the sialyl donor with (3-fluoroacetamidopropyl)-2-acetamido-2-deoxy-3-O- (2,3,4,6-tetra-O-acetyl)-beta-D-galactopyranosyl)-alpha-D-galactopyranos ide affords acetylated trifluoroacetamidopropyl glycoside Neu5Ac(alpha 2-->6)[Gal(beta 1-->3)]GalNAc alpha-OSp in a yield of 15% and the corresponding Neu5Ac(beta 2-->6)-anomer in a yield of 12%. After O-deacetylation and N-detrifluoroacetylation, these sialylbiosides can be used as ligands in preparing neoglycoconjugates.

[Mono- and polyvalent synthetic sialosides as inhibitors of Mycoplasma pneumoniae adhesiveness]. / Mono- i polivalentnye sinteticheskie sialozidy kak ingibitory adgezivnosti Mycoplasma pneumoniae.

Nine mono- and polyvalent sialosides as substances inhibiting adhesive properties of mycoplasma Mycoplasma pneumoniae--the agent of human atypical pneumonia have been studied in the reaction of hemagglutination (RHA) using solid-phase variant of ELISA-test ("sandwich"--variant), which is based on the competition for specific binding in RHA between the studied syalosides and sialylglycoproteins of fetuin conjugate with horseradish peroxidase. Of seven polymers--P alpha.12.ONa(N1), P alpha.12.EA(N2), P alpha.12.NH2(N3), P alpha.12.AES.10.ONa(N4), P alpha.12.Hg.20.ONa(N6), P20.SLea.NH2(N7), as well as monomer alpha-Bn Neu5Ac and fucoidan the polymers 5, 2, 4 and 7 in concentrations as to the content of sialic acid 1.0; 1.3; 1.35 and 10.0 M, respectively, most efficiently (up to 98%) inhibited the adhesiveness of M. pneumoniae. Polymeric sialosides 3, 6 and 1 proved less active and, the concentration of sialic acid in the composition of their molecules being 10.0 microM, inhibited adhesiveness of M. pneumoniae by approximately 77, 75 and 62.5%, respectively. Antiadhesive activity of fucoidan and monomer proved too low under concentration of these substances as to the content of sialic acid in them 25 microM: they decreased the ability to adhesion in M. pneumoniae by 33 and 56%, respectively. This proved that polyvalent sialosides 2, 4, 5 and 7 are promising for creation of drugs for treatment and prophylaxis of human pneumonias of mycoplasmal etiology on principally new basis with regard for the properties of the disease agent.

[The inhibition of Mycoplasma pneumoniae adhesion in a fetuin test system by synthetic analogs and polymeric forms of neuraminic acid]. / Ingibirovanie adgezii Mycoplasma pneumoniae v fetuinovoi test-sisteme sinteticheskimi analogami i polimernymi formami neiraminovoi kisloty.

Eight glycosides and structural analogues of neuraminic acid as well as eight polymeric forms of N-acetyl neuraminic acid have been studied for their inhibitory effect on adhesion of Mycoplasma pneumoniae. Maximum inhibiting effect among low-molecular compounds was manifested by 2-->3 sialyllactose which, being used in concentrations 5.0 and 10.0 micrograms/ml, inhibited adhesion of mycoplasmas by 76 and 87%, respectively. These indices for other derivatives in the above mentioned concentrations were as follows (%): 2-->6 sialyllactose, 31 and 74%; alpha-Me-glycoside NeuAc, 75 and 85%; alpha-Bn-glycoside-N-trifluoruracetyl NeuAc, 30 and 63%; alpha-Bn-glycoside NeuAc, 32 and 59%; alpha-Bn-glycoside-4-epi-NeuAc, 20 and 27%; beta-Bn-glycoside NeuAc, 2-4%; beta-me-glycoside NeuAc, 4-5%. The maximum inhibiting effect (50% inhibition at concentration 2.5 mumol) among polymeric forms was exerted by the conjugate alpha-benzeneglycoside with polyacrylic acid containing 12 mol% of NeuAc. Conjugates with 8, 16 and 20 mol% of NeuAc possessed a bit less activity. The 50% concentration for them was 5.3, 3.1 and 8.3 mumol, respectively. Polymeric forms on the basis of polyacrylamide proved less active.

[Synthesis of a repeating unit and the dimer of the repeating unit of the major chain of Shigella flexneri O-antigen polysaccharide]. / Sintez povtoriaiushchegosia zvena i dimera povtoriaiushchegosia zvena osnovnoi tsepi O-antigennykh polisakharidov Shigella flexneri.

Methyl glycoside of the tetrasaccharide GlcNAc(beta 1-2)Rha(alpha 1-2)Rha(alpha 1-3)Rha, which represents a repeating unit of the basic chain of Shigella flexneri O-antigenic polysaccharides, was synthesized using acylated monosaccharide synthons. A dimer of the repeating unit, octasaccharide [GlcNAc(beta 1-2)Rha(alpha 1-2) Rha(alpha 1-3)Rha(alpha 1-3)]2-OMe was obtained by TrClO4-catalyzed condensation of two tetrasaccharide blocks.

[Synthesis of oligosaccharide fragments of O-specific polysaccharides of Shigella flexneri. III. Synthesis of the tetrasaccharide Glc alpha 1-3Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe and the pentasaccharide GlcNAc beta 1-2(Glc alpha 1-3)Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe]. / Sintez oligosakharidnykh fragmentov O-spetsificheskikh polisakharidov shigella flexneri. III. Sintez tetrasakharida Glc alpha 1-3Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe i pentasakharida GlcNAc beta 1-2 (Glc alpha 1-3)Rha alpha 1-2(Glc alpha 1-3)Rha alphal-OMe.

Two synthetic schemes to prepare the title branched tetrasaccharide and pentasaccharide are described. These oligosaccharides represent fragments of the O-antigenic polysaccharides of Shigella flexneri serotype 5b.

[Synthesis of oligosaccharide fragments of O-specific Shigella flexneri polysaccharides. II. Synthesis of trisaccharide Glc alpha1----3RHa alpha1----2Rha alpha1----OMe and tetrasaccharide GlcNAc beta1----2(Llc alpha1----3)Rha alpha1----2Rh alpha1----OMe]. / Sintez oligosakharidnykg fragmentov O-spetsificheskikh polisakharidov Shigella flexneri. II. Sintez trisakharida Glc alpha1----3Rha alpha1----OMe i tetrasakharida GlcNAc beta1----2(Glc alpha----3)Rha alpha1----OMe.

Methyl glycosides of the title linear trisaccharide and branched tetrasaccharide were synthesized by stepwise glycosylation. These oligosaccharides represent the fragments of O-antigenic polysaccharides of Shigella flexneri serotypes 2b, 3a, 5b, and X.