Synthesis of 1,2:5,6-Di-O-isopropylidene-3-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose and 1,2-Mono-O-isopropylidene-6-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose

1,2:5,6-Di-O-isopropylidene-3-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose and 1,2-mono-O-isopropylidene-6-O-[3-(uracil-1-yl)propionoyl]-α-D-glucofuranose were synthesized.     

Synthesis of lipooligosaccharides related to nodulation factors ofRhizobium sp. NGR234

Trisaccharide analogs of natural nodulation factors fromRhizobium sp. NGR234, namely, 2-acetamido-2-deoxy-4-O-(2-deoxy-2-hexadecanamido-β-d-glucopyranosyl)-6-O-(2-O-methyl-α-l-fucopyranosyl)-d-glucopyranose and its derivatives containing a 4-O-acetyl or a 3-O-sulfo group at thel-fucose residue, were synthesized. The oligosaccharides synthesized were shown to posses biological activity. Laboratoire de Biologie Moléculaire des Plantes Supérieures (LBMPS), Université de Genève, 1 ch. de l'Impératrice, 1292 Chambesy-Genève, Suisse. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya No. 3, pp. 513–518, March, 1998.     

Synthesis of Methyl 2-Acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopyranoside

Methyl-2-acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopy-ranoside has been synthesized by conversion of methyl 2-amino-2-deoxy-4,6-O-benzylidene-α-D-altropyranoside into the corresponding 3-O-methanesulfony1-2-N-[(methylthio)thiocarbonyl]derivative followed by intramolecular displacement of the 3-O-methanesulfonyloxy group with the (methylthio)thiocarbamoyl group.     

Synthesis of Xanthone-O-Glycosides. II.. Synthesis of 1-O-β-glycosides

Several naturally occurring xanthone-1-O-glycosides have been synthesized in order to study monoamine oxidase (MAO) inhibition structure-activity relationships. The syntheses also confirmed the structures as 1-β-D -glucosyloxy-3-hydroxy-5-methoxyxanthone (Canscora decussata SCHULT .), 1-O-β-primeverosyl-3, 7, 8-trimethoxyxanthone (decussatin-1-O-primeveroside, Gentiana verna L .) and 1-O-β-primeverosyl-3, 8-dimethoxy-7-hydroxyxanthone (gentiacaulein-1-O-β-primeveroside, Gentiana verna L .).     

Synthesis of Tri-And Tetrasaccharides Present in the Linkage Region of Heparin and Heparan Sulphate

Abstract

The methyl glycosides of the the tri-and tetrasaccharides present in the linkage region of heparin, methyl O-(β-D-galactopyranosyl)-(l→3)-O-(β-D-galactopyranosyl)-(l→4)-β-D-xylopyranoside and methyl O-(β-D-glucopyranosyluronic acid)-(l→3)-O-(β-D-galactopyranosyl)-(l→3)-O-(β-D-galactopyranosyl)-(l→4)-β-D-xylopyranoside sodium salt, were synthesized together with their phosphate containing analogues, methyl O-(β-D-galactopyranosyl)-(l→3)-O-(β-D-galactopyranosyl)-(l→4)-β-D-xylopyranoside 2-(disodium phosphate) and methyl O-(β-D-glucopyranosyluronic acid)-(l→3)-O-(β-D-galactopyrano-syl)-(l→3)-O-(β-D-galactopyranosyl)-(l→4)-β-D-xylopyranoside 2-(disodium phosphate) sodium salt, which are glycosides of the structure found in the linkage region of heparan sulphate.     

Synthesis of Tetrasaccharide Repeating Unit of the K-Antigen from Klebsiella Type-16

Abstract

Starting from L-fucose, D-glucose and lactose, methyl O-[2,3-di-O-benzoyl-4, 6-O-(4-methoxybenzylidene)-β-D-glucopyranosyl]-(1→4)-2,3-di-O-benzoyl-α-L-fucopyranoside and methyl O-(2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl)-(1→4)-O-(2,3,6-tri-O-benzyl-α-D-glucopyranosyl)-(1→4)-O-(methyl 2,3-di-O-benzoyl-β-D-glucopyranosyluronate)-(1→4)-2,3-di-O-benzoyl-α-L-fucopyranoside were synthesized. Removal of protecting groups gave the tetrasaccharide repeating unit of the antigen from Klebsiella type-16 in the form of its methyl ester methyl glycoside.     

Introduction of a New Class of Ligands for the Metal-Catalyzed Enantioselective Synthesis

Protected thiosugars were prepared as ligands for the metal-catalyzed enantioselective synthesis. The protecting groups in these ligands were varied to test a proposed new concept for the metal-catalyzed enantioselective synthesis. This new concept centres on the use of a stair-like ligand with a large substituent on one side and a small substitutent on the other rather than the commonly employed ligands which have C₂ symmetry (see Fig.3). In such a ligand, both substituents should have a major influence on the coordination of a prochiral substrate. To test this proposal, 3-thio-α-D -glucofuranose derivatives with the following substituents were synthesized: 1,2-O-isopropylidene-5,6-O-methylidene (see 24 ), 1,2:5,6-di-O-isopropylidene (see 2 ), 5,6-O-cyclohexylidene-1,2-O-isopropylidene (see 23 ), 1,2-O-cyclohexylidene-5,6-O-isopropylidene (see 14 ), 1,2:5,6-di-O-cyclohexylidene (see 13 ), 5,6-O-(adamantan-2-ylidene)-1,2-O-isopropylidene (see 21 ), and 1,2:5,6-di-O-(adamantan-2-ylidene) (see 25 , Table 2). As a representative of the allofuranoses, 1,2:5,6-di-O-isopropylidene-3-thio-α-D -allofuranose ( 6 ) was chosen. The following derivatives of 1,2-O-isopropylidene-α-D -xylofuranose were also synthesized: 1,2-O-isopropylidene-5-deoxy-3-thio-α-D -xylofuranose ( 29 ), 1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 28 ) and 5-O-[(tert-butyl)-diphenylsilyl]-1,2-O-isopropylidene-3-thio-α-D -xylofuranose ( 15 , see Table 2). The proposed concept was tested using the copper-catalyzed 1,4-addition of BuMgCl to cyclohex-2-en-1-one. The enantioselectivity was very dependent on the ligand used and was up to 58%.     

Synthesis of brain-targeted 5-iodo-, 5-vinyl- and (E)-5-(2-iodovinyl)-2′-deoxyuridines coupled to a dihydropyridine ⇌ pyridinium salt redox chemical delivery system

5-Iodo-3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (15a) , 5-vinyl-3′-O-(1-methyl-1,4-di-hydropyridyl-3-carbonyl)-2′-deoxyuridine (15b) and (E)-5-(2-iodovinyl)-3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl)-2′-deoxyuridine (15c) were synthesized for future evaluation as lipophilic brain-selective antiviral agents for the treatment of herpes simplex encephalitis. Quaternization of the 3′-O-(3-pyridylcarbonyl) compounds 10–11 using iodomethane afforded the corresponding 1-methylpyridinium salts 12–13 which were reduced with sodium dithionite to yield the corresponding 3′-O-(1-methyl-1,4-dihydropyridyl-3-carbonyl) compounds 14–15.     

Nucleotides,Part LX,Synthesis and Characterization of New 2′-O-Methylriboside 3′-O-Phosphoramidites Useful for the Solid-Phase Synthesis of 2′-O-Methyloligoribonucleotides

A series of new 2′-O-methylribonucleoside 3′-O-[2-(4-nitrophenyl)ethyl dialkylphosphoramidites] 27 – 31 , 33 – 38 , 40 – 44 , and 45 – 50 were synthesized and their stability and reactivity compared in automated oligonucleotide synthesis with the standard 2′-O-methylribonucleoside 3′-O-(β-cyanoethyl diisopropylphosphoramidites) 32 , 39 , 45 , and 51 , respectively. The 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) groups were used for the protection of the base moieties.     

Syntheses of 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one,an isostere of oxanosine,and the guanosine analog 6-amino-1-(β-d-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one via ring closure of pyrazole-5-thioureido intermediates

6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 4 ), an isostere of the nucleoside antibiotic oxanosine has been synthesized from ethyl 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxylate ( 6 ). Treatment of 6 with ethoxycarbonyl isothiocyanate in acetone gave the 5-thioureido derivative 7 , which on methylation with methyl iodide afforded ethyl 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-ethoxycarbonyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxylate ( 8 ). Ring closure of 8 under alkaline media furnished 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 10 ), which on deisopropylidenation afforded 4 in good yield. 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 5 ) has also been synthesized from the AICA riboside congener 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxamide ( 12 ). Treatment of 12 with benzoyl isothiocyanate, and subsequent methylation of the reaction product with methyl iodide gave 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-benzoyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxamide ( 15 ). Base mediated cyclization of 15 gave 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 14 ). Deisopropylidenation of 14 with aqueous trifluoroacetic acid afforded 5 in good yield. Compound 4 was devoid of any significant antiviral or antitumor activity in culture.     

Syntheses of Novel Nonreducing-Sugar Subunit Analogs of Lipid a Carrying 2-Acyloxytetradecanoyl and 2-Hydroxyacyl Groups of Different Carbon Chain Length

Abstract

To investigate the biological influence of the 2-(acyloxy)tetradecanoyl and 2-hydroxyacyl groups in the nonreducing-sugar subunit analogs of lipid A, a novel series of 3-(O-[(2RS)-2-acyloxytetradecanoyl]-2-deoxy-2-[(2RS)-2-hydroxytetradecanamido]-4-O-phosphono-d-glucoses (10a-d), 3-O-[(2RS)-2-acyloxytetradecanoyl]-2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-4-O-phosphono-d-glucoses (19a-d), and 2-deoxy-2-[(2RS)-2-hydroxyacyl]amino-4-O-phosphono-3-O-[(3R)-3-tetradecanoyloxytetradecanoyl]-d-glucoses (23e-h) were systematically synthesized.     

Synthesis of Polyacrylamide Copolymers Containing (1→6)-Branched (1→3)-β-D-Linked Tri- and Tetra-Saccharides Related to Schizophyllan

Abstract

The allyl β-glycosides of a trisaccharide O-β-D-Glcp-(1→3)-O-[β-D-Glcp-(1→6)]-β-D-Glcp and of a tetrasaccharide O-β-D-Glqp-(1→3)-O-[β-D-Glqp-(1→6)]-O-β-D-Glcp-(1→3)-β-D-Glcp, corresponding to the branching point or the repeating unit of antitumor (1→6)-branched-(1→3)-β-D-glucans, have been synthesized starting from ethyl 2-O-benzoyl-4,6-O-benzylidene-l-thio-α-D-glucopyranoside and copolymerized in a radical reaction with acrylamide to obtain polyacrylamide copolymers containing the tri-and tetra-saccharides for immunochemical studies of schizophyllan.     

Cyclodextrin derivatives for GC separation of racemic mixtures of volatile compounds. Part VIII: 2,6-di-O-methyl-3-O-pentyl-γ-cyclodextrin and 2,6-di-O-methyl-3-O-(4-oxo-pentyl)- and 2,6-di-O-pentyl-3-O-(4-oxo-pentyl)-β-and -γ-cyclodextrins

In pre vious papers, 2,6-di-O-methyl-3-O-pentyl-β-cyclodextrin (CD) was demonstrated to be successful in separating volatile compounds, while avoiding the drawbacks of 2,3,6-tri-O-methyl-O-methyl-β-CD in terms of column stability and operating temperature. Since a CD chiral selector of universal use has not yet been found, and at least two (or more) columns coated with different CD derivatives are therefore necessary for routine work, the performance of 2,6-di-O-methyl-3-O-pentyl-γ-CD, 2,6-di-O-methyl-3-O-(4-oxopentyl)-γ-CD, 2,6-di-O-pentyl-3-O-(4-oxo-pentyl)-β-CD, and 2,6-di-O-pentyl-3-O-(-4-oxo-pentyl)-γ-CD diluted in polysiloxanes for the separation of volatile compounds in aromas and essential oils will be illustrated; each column coated with each of the newly synthesized CD derivatives was evaluated by analyzing more than 150 different recemates with different structures.     

Large-Scale Synthesis of a Lewis b Tetrasaccharide Derivative,its Acrylamide Copolymer,and Related DI- and Trisaccharides for Use in Adhesion Inhibition Studies with Helicobacter Pylori.

ABSTRACT

The 2-aminoethyl glycoside of O-α-L-fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→3)-[O-α-L-fucopyranosyl-(1→4)]-2-acetamido-2-deoxy-β-D-glucopyranose (Lewis B tetrasaccharide) was synthesized on a large scale and acryloylated with acryloyl chloride. The obtained oligosaccharide 2-acrylamidoethyl glycoside was then copolymerized with acrylamide to form a water-soluble, high molecular weight polymer, suitable for use in adhesion inhibition studies with Helicobacter pylori. Also synthesized were the corresponding derivatives of O-α-L-fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranose and O-β-L-fucopyranosyl-(1→2)-β-D-galactopyranose.

     

Synthesis of oligosaccharides related to the HNK-1 antigen. 5. Synthesis of a sulfo-mimetic of the HNK-1 antigenic trisaccharide

2-Aminoethyl 3,6-di-O-sulfo-β-D-glucopyranosyl-(1→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside, which is the sulfo-mimetic of the antigenic trisaccharide HNK-1, and the corresponding monosulfates, viz., 2-aminoethyl 3-O-sulfo-and 2-aminoethyl 6-O-sulfo-β-D-glucopyranosyl-(1→3)-β-D-galactopyranosyl-(1→ 4)-2-acetamido-2-deoxy-β-D-glucopyranosides, were synthesized. 2-Azidoethyl 2,4-di-O-benzoyl-β-D-glucopyranosyl-(1→3)-2,4,6-tri-O-benzoyl-β-D-galactopyranosyl-(1→ 4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside served as the common precursor for the sulfated trisaccharides. This compound was synthesized according to the [2+1] pattern from monosaccharidic precursors: 3,6-di-O-acetyl-2,4-di-O-benzoyl-D-glucopyranosyl trichloroacetimidate, allyl 2-O-benzoyl-4,6-O-benzylidene-β-D-galactopyranoside, and 2-azidoethyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside. The structures of the glycosyl donors and glycosylation conditions were optimized for the efficient synthesis of the glucosyl-β-(1→3)-galactose disaccharide block and its subsequent transformation into the target trisaccharide sequence. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1593–1607, August, 2007.     

Synthesis of a Trisaccharide Repeating Unit Related to Arabinogalactan-Protein (AGP) Polysaccharides 1

Abstract

Starting from L-arabinose and methyl β-D-galactopyranoside, methyl 2,3,4-tri-O-benzyl-6-O-[2,4,6-tri-O-benzoyl-3-O-(23,5-tri-O-benzoyl-α-L-arabinofuranosyl)-β-D-galactopyranosyl]-β-D-galactopyranoside 10 has been synthesized. Removal of protecting groups gave the methyl glycoside 12 of a trisaccharide representative of a repeating unit of arabinogalactan (AGP) polysaccharides.

     

Synthetic Studies on Sialoglycoconjugates 89: Synthesis of Ganglioside GM3 and KDN-GM3 Containing Different Carbon-Chain Length Fatty Acyl Groups at the Ceramide Residue

ABSTRACT

Ganglioside GM₃ and KDN-ganglioside GM₃, containing hexanoyl, decanoyl, and hexadecanoyl groups at the ceramide moiety have been synthesized. Selective reduction of the azido group in O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-(3-O-acetyl-2,6-di-O-benzoyl-β-D-glucopyranosyl)-(1→1)-(2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (1) and O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-(3-O-acetyl-2,6-di-O-benzoyl-β-D-glucopyranosyl)-(1→1)-(2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (2), coupling with hexanoic, decanoic, and hexadecanoic acids, O-deacylation, and de-esterification gave the title gangliosides GM₃ (11→13) and KDN-GM₃ (14→16) in good yields. On the other hand, O-deacylation of 1 and subsequent de-esterification gave 2-azido-sphingosine containing-GM₃ analogue 17, which was converted into lyso-GM₃, in which no fatty acyl group was substituted at the sphingosine residue, by selective reduction of the azido group.     

Mimics of the Structural Elements of Type III Group B Streptococcus Capsular Polysaccharide. Part I: Synthesis of a Carboxylate-Containing Pentasaccharide

Abstract

A carboxylate-containing pentasaccharide, methyl O-(β-d-galactopyranosyl)-(1→4)-O-(β-d-glucopyranosyl)-(1→6)-O-{3-O-[(S)-1-carboxyethyl]-β-d-galactopyranosyl-(1→4)-O}-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-β-d-galactopyranoside (27) was synthesized by block condensation of suitably protected donors and acceptors. Phenyl 3-O-benzyl-4,6-di-O-chloroacetyl-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside (17) was condensed with methyl 2,4,6-tri-O-benzyl-β-d-galactopyranoside (4) to afford a disaccharide, methyl O-(3-O-benzyl-4,6-di-O-chloroacetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (18). Removal of chloroacetyl groups gave 4,6-diol, methyl 0-(3-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (19), in which the primary hydroxy group (6-OH) was then selectively chloroacetylated to give methyl O-(3-O-benzyl-6-O-chloroacetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (20). This acceptor was then coupled with 2,4,6-tri-O-acetyl-3-O-[(S)-1-(methoxycarbonyl)ethyl]-α-d-galactopyranosyl trichloroacetimidate (14) to afford a trisaccharide, methyl O-{2,4,6-tri-O-acetyl-3-O-[(S)-l-(methoxycarbonyl)ethyl]-β-d-galactopyranosyl}-(1→4)-O-(3-O-benzyl-6-O-chloroacetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-d-galactopyranoside (21). Removal of the 6-O-chloroacetyl group in 21 gave 22, which was coupled with 4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-2,3,6-tri-O-acetyl-α-d-glucopyranosyl trichloroacetimidate (23) to yield protected pentasaccharide 24. Standard procedures were used to remove acetyl groups and the phthalimido group, followed by N-acetylation, and debenzylation to yield pentasaccharide 27 and a hydrazide by-product (28) in a 5:1 ratio, respectively. Compound 27 contains a complete repeating unit of the capsular polysaccharide of type III group B Streptococcus in which terminal sialic acid is replaced by an (S)-1-carboxyethyl group.     

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.

     

Preparation of trans Diequatorial 2,3-Pyruvate Acetals in a Di- and a Trisaccharide Related to the K-Antigen from E. Coli 0101:K103:H−

Abstract

Using methyl 2,2-bis(ethylthio)propionate as acetalating agent and triflic acid-sulfuryl chloride as catalyst, synthesis of 2,3-trans diequatorial pyruvate ketal was achieved. Starting from D-galactose and L-rhamnose derivatives, methyl 2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl-(1→4)-6-O-benzyl-2,3-O-(1-methoxycarbonyl)ethylidene- α-D-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside and methyl 4,6-di-O-benzyl-2,3-O-(1-methoxy-carbonyl)ethylidene-α-D-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside were synthesized. Removal of the protecting groups from the former, afforded the trisaccharide repeating unit of the K-antigen from E.coli O101:K103:H^? in the form of its methyl glycoside methyl ester.