Synthesis of p-Trifluoroacetamidophenylethyl O-(2-Acetamido-2-Deoxy-β-D-Galactopyranosyl)-(1→4)-O-β-D- Galactopyanosyl-(1→4)-O-β-D-Glucopyranoside,Containing the Trisaccharide Portion of the Asialo-GM2 Glycolipid

ABSTRACT

The p-trifluoroacetamidophenylethyl β-glycoside 9 of the trisaccharide O-(2-acetamido-2-deoxy-β-D-galactopyranosyl)-(1→4)-O-β-D-galactopyranosyl-(1→4)-D-glucopyranose (gangliotriose, asialo-GM2) was synthesised. The key step was coupling of a suitably protected lactose derivative with a galactosamine thioglycoside derivative using sulfuryl chloride/trifluoromethanesulfonic acid activation.     

Synthesis of O-(2-Acetamido-2-Deoxy-β-D-Glucopyranosyl)-(l→2)-O-α-D-Mannopyranosyl-(l→6)-O-β-D-Glucopyranosyl-(1→4)-2-Acetamido-2-Deoxy-D-Glucopyranose. A Potential Acceptor-Substrate for N-Acetylglucosaminyltransferase-V (GnT-V)

Abstract

The reaction of phenyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthaIimido-l-thio-β-D-glucopyranoside with methyl 3,4,6-tri-O-benzyl-α-D-mannopyranoside catalysed by iodonium ion (TfOH-NIS) followed by deacylation-acetylarion afforded disaccharide 11. which was readily converted (in four steps) to bromide 12. A similar glycosylarion with phenyl 2,3,4,6-tetra-O-acetyl-l-thio-D-glucopyranoside of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside 16 followed by O-deacetylation of the resulting intermediate gave disaccharide 18. The 4,6-O-benzylidene derivative of 18 was acetylated then deacetaled to give diol 21. This diol acceptor was condensed with bromide 12 (promoted by mercuric cyanide) to give the partially protected tetrasaccharide derivative 22 which was O-deacetylated and then subjected to catalytic hydrogenation to furnish the title tetrasaccharide 6. The structure assigned to 6 was supported by ¹H and ¹³C NMR spectral data and FAB mass spectroscopy.     

Synthesis of Two Isomeric Tetrasaccharides 0-α-L-Fucopyranosyl-(1→3) and (1→4)-0-(2-Acetamido-2-Deoxy-β-D-Glucopyranosyl)-(1→3)-0-(β-D-Galactopyranosyl)-(1→4)-D-Glucopyranose and a Related Tetrasaccharide 0-α-L-Fucopyranosyl-(1→3)-0-(2-Acetamido-2-Deoxy-β-D-Glucopyranosyl-(1→6)-0-(β-D-Galactopyranosyl)-(1→4)-D-Glucopyranose

ABSTRACT

Synthesis of three tetrasaccharides, namely, 0-α-L-fucopyranosyl-(1→3)-0-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-0-(β-D-galactopyranosyl)-(1→4)-β-D-glucopyranose (7), 0-α-L-fucopyranosyl-(1→4)-0-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1→3)-0-(β-D-galactopyranosyl)-(1→4)-D-glucopyranose (9), and 0-α-L-fucopyransoyl-(1→3)-0-(2-acetamido-2-deoxy-β-D-glucopyransoyl)-(1→6)-0-(β-D-galactopyranosyl)-(1→4)-D-glucopyranose (15) has been described. Their structures have been established by ¹³C NMR spectroscopy.     

Synthesis of O-[4,6-Di-O-Acetyl-4-O-(2,3,4,6-Tetra-O-Acetyl-β-D-Galactopyranosyl)-2-Deoxy-2-Hydroxyimino-D-Arabino-Hexopyranosyl]-N-Benzyloxycarbonyl-L-Serine Methyl Esters And Their Transformations

ABSTRACT

3,6-Di-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-2-deoxy-2-hydroxyimino-α- and -β-D-arabino-hexopyranosides of N-benzyloxycarbonyl-L-serine methyl ester as well as of ethanol have been synthesised from D-lactal hexaacetate via nitrosyl chloride, followed by condensation with L-serine derivatives and ethanol, respectively. The compounds of L-serine thus obtained were modified at C-2 and C-3 to afford L-serine derivatives attached to disaccharides containing terminal α-D-gluco-, 2-acetamido-α-D-gluco-, β-D-manno, 2-acetamido-β-D-manno-pyranosyl, 3-azido-2-hydroxyimino-α-D-arabino-, and α-D-ribo-hexopyranosyl residues.     

Preparation and Characterization of 61,6n-DI-O-(α-D-Galactopyranosyl)Cyclomaltooctaoses

ABSTRACT

Four positional isomers of 6¹,6ⁿ-di-O-(D-galactopyranosyl)cyclomaltooctaoses (cG₈s, γ-cyclodextrins) (n = 2?5) were chemically synthesized using the trichloroacetimidate method. The desired compounds having two α-(1→6)-linkages were isolated from a mixture of configurational isomers by HPLC, and their structures were confirmed by ¹³C NMR spectroscopy and FAB-high resolution mass spectra (HRMS). The elution behavior of their four positional isomers on an ODS column by HPLC is discussed.     

Syntheses of Model Oligosaccharides of Biological Significance. VI. Glycosylation at C-3 of Galactose: A Synthesis of Trideuterio-Methyl 3-O-(-Acetamido-2-Deoxy-β-D-Glucopyranosyl)-β-D-Galactopyranoside

The title disaccharide was prepared by glycosylation of either methyl trideuteriomethyl 2-O-benzoyl-4,6-benzylidene-β-D-galactopyranoside or trideuteriomethyl-4,6-O-benzylidene-β-D-galactopyranoside with 3,4,6-tri-Oi-acetyl 2-deoxy-2-phthalimido-β-D-glucopyranosyl bromide using silver zeolite 13X or silver triflate as promoters.     

X-Ray Crystallographic Investigation of Fully Acetylated N-(2-Deoxy-2-Acetamido-β-D-Glucopyranosyl)Alkanamides as N-Glycoprotein Linkage Region Analogs

To understand the structural significance of the linkage region of N-glycoproteins, three title sugar amides have been prepared as analogs and their molecular assembly and crystal structures have been solved to explore the effect of acetyl protection and aglycon variation on the conformation, particularly of the N-glycosidic linkage. Comparative analysis of these structures with those of free sugar amides reported earlier showed that conformation of the amido aglycon moiety is not altered significantly by the masking of hydroxyl groups in the form of acetate. The bifurcated antiparallel pattern involving N?H…O and C?H…O hydrogen bonds, a hallmark of the N-glycoprotein models GlcNAcβNHAc and GlcNAcβAsn, is absent in all of the fully protected title alkanamides. The asymmetric unit of the tri-O-acetylated GlcNAcβNHAc contains two different conformations, in one of which the double-pillared hydrogen bond network involving C1 and C2 acetamido groups is antiparallel, while it is parallel in the other. The co-occurrence of a molecular assembly motif—a double-pillared parallel and antiparallel hydrogen bonding pattern—is hitherto unknown in the crystal structures of N-glycoprotein linkage region models and analogs.     

Efficient Syntheses of Methyl 2-Amino-2-Deoxy-3,4,6-Tri-O-Benzyl-α-D-Glucopyranoside and its 2-tert-Butoxycarbonylamino- and 2-Methylamino Derivatives from N-Acetyl-D-Glucosamine

ABSTRACT

The synthesis of the title compounds started with N-acetylglucosamine which was converted into the corresponding methyl glycoside and O-protected with benzyl groups. Subsequent N-protection as its N-BOC-N-acetyl derivative and sequential removal of the N-acetyl group and of the BOC group led in good yield to the target compounds in multigram amounts.     

Synthesis of 6-S-(5-Acetamido-3,5-Dideoxy-D-Glycero-α-D-Galacto-2-Nonulopyranosylonic Acid)-6-Thio-Hexopyranosides

The reaction of the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulo-pyranosonate with a variety of 6-bromo-6-deoxy-D-hexopyranosides, such as methyl 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-α-D-glucopyranos-ide, -galactopyranoside, allyl 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-β-D-glucopyranoside, and allyl 2-acetamido-3,4-di-O-acetyl-6-bromo-2,6-dideoxy-β-D-glucopyranoside, gave the corresponding (2→6)-linked disaccharides, α-glycosides of 2-thio-N-acetylneuraminic acid derivative in good yields. These disaccharides were converted, via O-deacetylation, followed by hydrolytic removal of the ester group, into the title compounds.     

Synthetic Mucin Fragments: Methyl-3-O-(2-Acetamido-2-Deoxy-4-O- and 6-O-β-D-Galactopyranosyl-β-D-Glucopyranosyl)-β-D-Galactopyranoside and Methyl 3-O-(2-Acetamido-2-Deoxy-4-O- and 3-O-Methyl-β-D-Glucopyranosyl-3-D-Galactopyranoside

Abstract

Glycosylation of methyl 3-O-(2-acetamido-3, 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (1), catalyzed by mercuric cyanide, afforded a trisaccharide derivative, which was not separated, but directly O-deacetylated to give methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-giucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (8). Hydrogenolysls of the benzyl groups of 8 then furnished the title trisaccharide (9). A similar pflyccsylation of methyl 3-O-(2-acetamido-3-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl- β-D-galactopyranoside (obtained by acetylation of 4, followed by hydrolysis of the benzylidene acetal group) with bromide 1 gave a tribenzyl trisaccharide, which, on catalytic hydrogenolysls, furnished the isomeric trisaccharide (12). Methylation of 4 and 2 with methyl iodide-silver oxide in 1:1 dichloro-methane-N, N-dimethylformamide gave the 3-O- and 4-O-monomethyl ethers (13) and (15), respectively. Hydrogenolysis of the benzyl groups of 13 and 15 then provided the title monomethylated disaechartdes (15) and (16), respectively. The structures of trisacchacides 9 and 12, and disaccharides 14 and 16 were all established by ¹³C MMR spectroscopy.     

Stereocontrolled Conversion of Allylic Alcohols Into Vicinal Cis-Diols: New Syntheses of Methyl α-L-Digitoxoslde and Methyl 2-Deoxy-α-L-Fucoside

A synthetic process is outlined in which an allylic alcohol is converted into its primary urethane derivative, which is then subjected to iodonium ion induced cyclization to give a single iodo-carbonate. The carbonate is then deiodinated reductively and hydrolyzed to afford the vicinal diol. By use of this process the two title sugars have been prepared from methyl 2.3.6-trideoxv-α-L-ervthro-hex-2-enopvranoside and its α-L-threo counterpart.     

Convenient Preparation of 2-Deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranosyl Chloride

By using acetyl chloride as HCl generator, the procedure for the Hoffer preparation of the α-chloro sugar 4a was significantly improved. The α-configuration of the chloro atom was confirmed by using NOE measurement. Sequential transformation of 4a to the β-anomer and to the furfuryl derivative 6 was studied.     

Synthesis of Methyl O-β-D-Ouactopyrmosyl-(1+6)-(3-Deoxy-3-Fluoro-β-D-Galactopyranosyl)-(1→6)-β-D-Galactopyranoside. Confirmation of the Location of Subsite D in the Monoclonal IgA J539

Bromoacetylation of methyl 2,4-di-O-benzoyl-3-deoxy-3-fluoro-β-D-galactopyranoside, followed by the cleavage of the methoxy group from the resulting 6-O-bromoacetyl derivative 2 with 1,1-dichloromethyl methyl ether gave 2,4-di-0-benzoyl-6-0-bromoacetyl-3-deoxy-3-fluoro-α-D-galactopyranosyl chloride (3). Reaction of 3 with methyl 2,3,4-tri-O-benzoyl-β-D-galactopyranoside promoted by silver trifluoromethanesulfonate afforded methyl 0-(2,4-di-O-benzoyl-6-O-bromoacetyl-3-deoxy-3-fluoro-β-D-galacto-pyranosyl)-(1→6)-2,3,4-tri-O-benzoyl-β-D-galactopyranoside (5). O-Debromoacetylation of 5 with thiourea gave the disaccharide nucleophile 6 which was condensed with 2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl bromide to afford the expected β-(trans)-linked trisaccharide derivative 7. Debenzoylation of 7 gave the methyl β-glycoside 8 of the (1→6)-linked D-galactotriose having the HO-3 of the internal residue replaced by a fluorine atom. Compound 8 was used to further delineate the subsites in the combining area of the monoclonal anti-(1→6)-β-D-galactan-specific immunoglobulin IgA J539.     

Synthesis of the 4-Deoxy-2-Deutero-4-Fluoro Analog of Methyl O-β-D-Galactopyranosyl-(1→6)-β-D-Galactopyranoside

ABSTRACT

Methyl 4-deoxy-4-fluoro-6-O-(β-D-galactopyranosyl)-(2-²H)-β-D-galactopyranoside was prepared by the condensation of 2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl bromide and methyl 2-O-benzoyl-3-O-benzyl-4-deoxy-4-fluoro-(2-²H)-β-D-galactopyranoside (17), followed by deprotection. The introduction of deuterium at C-2 in an intermediate methylhexopyranoside was achieved by a double inversion, brought about by oxidation of C-2 of a derivative of methyl α-D-glucopyranoside, to give the corresponding ketone, and subsequent reduction thereof with NaBD₄, to give a derivative with the D-manno configuration (8). Inversion of the configuration at C-2 of the latter was achieved by displacement with sodium benzoate of the O-trifluoromethanesulfonyl (triflyl) group in the 2-O-triflyl derivative of 8. The resulting synthon was converted, conventionally, to methyl 2-O-benzoyl-3-O-benzyl-6-O-trityl-(2-²H)-β-D-glucopyranoside. Its conversion into the 6-O-trityl derivative of 17, unsuccessful by treatment with dimethylaminosulfur trifluoride, was readily accomplished by the displacement of the triflyl group with fluoride ion contained in an ion-exchange resin.     

Action of Base on Methyl 6-Thio- (and 6-Deoxy-) 2-O-Methanesulfonyl-α-d-Glucopyranoside Derivatives1

Abstract

Treatment of methyl 4-O-benzoyl-3-O-tert-butyldiphenylsilyl-2-O-methanesulfonyl-6-thio-α-d-glucopyranoside (8) and its 6-deoxy analogue (11) with methanolic sodium methoxide, afforded methyl 2,3-anhydro-mannopyranoside derivatives as a consequence of an O₃ → O₄ TBDPS rearrangement. When the protecting group at C-3 was 2-methoxyethoxy methyl ether only deacylation and methanolysis of the methanesulfonyl group occurred.     

Stereoselective Syntheses of ALKYL- and ALKYL-2-THIO-α-Sialosides

ABSTRACT

Alkyl and thioalkyl α-glycosides of N-acetylneuraminic acid have been prepared in near quantitative yield and with complete stereoselectivity, under the Williamson reaction conditions using RONa or RSNa, respectively, in ROH or RSH as solvent.     

Syntheses and Properties of Tripicolinatechromium (Ⅲ)

Chromium (Ⅲ) has been implicated as glucose tolerance factor (GTF) in the maintenance of normal lipid and carbohydrate metabolism^[1]. Several organic chromium (Ⅲ) complexes containing nicotinate, amino acids ligand which have much higher biological activity than chromic chloride have been synthesized and extensively studied^[2]. Tripicolinatechromium (Ⅲ) as a new human chromium(Ⅲ) nutritional supplement was shown to reduce the symptoms of diabetes, hyperglycemia and cholesterol significantly^[3]. Although the crystal structure and NMR spectrum of tripicolinatechromium (Ⅲ) was studied previously^[4,5], Its properties have only received little attention. In this paper, we report the studies of syntheses and properties of tripicolinatechromium(Ⅲ).     

Syntheses of Methyl 2-O-, 3-O- and 6-O-(2′-Hydroxypropyl)-α-D-Glucopyranosides 1

Abstract

Methyl 6-O-, 3-O- and 2-O-(2′-hydroxypropyl)-α-D-glucopyranosides (4,8, and 12) were synthesized starting from methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside (1), methyl 4,6-O-benzylidene-α-D-glucopyranoside (5), and methyl 3-O-benzyl-4,6-O-benzylidene-D-glucopyranoside (9), respectively. Overall yields were 88%, 6% and 26% of 4, 8 and 12, respectively, with the 2-ether (12) being crystalline and the 3-ether (8) a single diastereomer.

     

Syntheses and Olfactory Characters of Some Endo-α-Substituted-Bicyclo[2. 2. 2]-Octenyl (or Octanyl) Methanols

Sixteen title compounds were synthesized, twelve of which are new ones. Their structures were determined by 1H NMR, IR and MS, the refractive indices or melting points were measured. Odors of all the title compounds were evaluated and the structure-odor relationship was briefly discussed.