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.

     

Synthesis of O-α-L-Fucopyranosyl-(1→2)-O-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-D-glucopyranose. The H-Blood Group Specific Trisaccharide

Abstract

Different reaction conditions were investigated for the preparation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (5). Compound 5 on reaction with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide afforded the 4-O-substituted 2-acetamido-2-deoxy-β-D-glucopyranosyl derivative which, on O-deacetylation, gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-glucopyranoside (8). The trimethylsilyl (Me₃Si) derivative of 8, on treatment with pyridineacetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having an O-acetyl group selectively introduced at the primary position and Me₃Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol to afford benzyl 2-acetamido-4-O-(6-O-acetyl-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside, which on isopropylidenation gave the desired, key intermediate benzyl 2-acetamido-4-O-(6-O-acetyl-3,4-O-isopropylidene-β-D-galactopyranosyl)-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside (12). Reaction of 12 with 2,3,4-tri-O-benzyl-α-L-fucopyranosyl bromide under catalysis by bromide ion afforded the trisaccharlde derivative from which the title trisaccharide was obtained by systematic removal of the protective groups. The structures of the final trisaccharide and of various intermediates were established by ¹H and ¹³C NMR 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 β-d-Glcp-(1→2)-[β-d-Ribf-(1→3)-]α-l-Rhap-(1→3)-α-l-Rhap-(1→2)-α-l-Rhap,THE REPEATING UNIT OF THE LIPOPOLYSACCHARIDE OF Acetobacter diazotrophicus PAL 5

A pentasaccharide, the major repeating unit of the lipopolysaccharide (LPS) of the nitrogen fixing bacterium Acetobacter diazotrophicus PAL 5 was efficiently synthesized as its allyl glycoside using a regio- and stereo-selective strategy. The key acceptor, allyl 3-O-acetyl-4-O-benzoyl-α-l-rhamnopyranoside (3), was prepared by selective 3-O-acetylation of allyl 4-O-benzoyl-α-l-rhamnopyranoside. Condensation of 3 with 2,3,4,6-tetra-O-benzoyl-α-d-glucopyranosyl trichloroacetimidate furnished the disaccharide 5. Deallylation and subsequent trichloroacetimidation of 5 afforded 2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl-(1→2)-3-O-acetyl-4-O-benzoyl-α-l-rhamnopyranosyl trichloroacetimidate (10). Selective 3-O-glycosylation of allyl α-l-rhamnopyranoside (1) with 10 followed by benzoylation gave trisaccharide (12), which could be conveniently converted to a donor (14). Condensation of 14 with allyl 3,4-di-O-benzoyl-α-l-rhamnopyranoside (15) gave tetrasaccharide 16. Selective deacetylation of 16 gave the acceptor 17 which was ribosylated to furnish the protected pentasaccharide, and finally deprotection led to the title compound.     

Synthesis of an antimetastatic tetrasaccharide β-D-Gal-(1→4)-β-d-GlcpNAc-(1→6)-α-D-Manp-(1→6)-β-D-Manp-OMe

An antimetastatic tetrasaccharide T₁,β-D-Gal-（1→4）-β-D-GlcpNAc-（1→6）-α-D-Manp-（1→6）-β-D-Manp-OMe,was synthesized with two approaches.The first approach was a conventional method employing thioglycoside and Koenigs-Knorr glycosylation reaction in 24%overall yield.The second one was a novel route through the azidoiodo-glycosylation strategy by using 2-iodo-2-deoxylactosyl azide as the donor in 36%overall yield.     

Synthesis and Structure of 1,2-O-(1-Aryl-1-Propylidene)-D-Mannitol

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Synthesis of propyl O-(α-L-rhamnopyranosyl)-(1→3)-[2,4-di-O-(2s-methylbutyryl)-α-L-rhamno-pyranosyl]-(1→2)-(3-O-acetyl-β-D-glucopyranosyl)-(1→2)-β-D-fucopyranoside,the tetrasaccharide moiety of Tricolorin A

Propyl O-(α-L-rhamncpyranosyl)-(1→3)-[2,4-di-O-(2s-methylbutyryl)-α-L-rham-nopyranosyl]-(1→2)-(3-O-acetyl-β-D-glucopyranosyl)-(1→2)-β-D-fucopyranoside (1), the tetrasac-charide moiety of Tricolorin A, was synthesized in total 23 steps with a longest linear sequence of 10 steps, and overall yield of 3.7% from D-Glucose. The isomerization of the dioxolane-type berzyli-dene in the presence of NIS/AgOTf was observed. Tetrasaccharide 1 exhibited no activity against the cultured P388 cell as Tricolorin A did.     

A General Method for Stepwise Elongation of the (1→5)-α-D-Arabinofuranan Chain

Condensation reaction of 3,5-di-O-benzoyl-1,2-O-(1-cyanoben-zylidene)-β-D-arabinofuranose (2) with benzyl and allyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-α-L-arabinofuranosides (5a and 5b) in methylene chloride in the presence of triphenylcarbenium tetrafluoroborate as catalyst under high vacuum gave α-(1→5)-linked dimeric D-arabinofuranoside derivatives (6a and 6b). One of the dimeric compounds (6a) was debenzoylated, triphenylmethylated, and rebenzoylated to give a dimeric homolog of 5a (8). Similarly for the preparation of 6a, 8 was condensed with 2 to provide an α-(1→5)-linked trimeric D-arabinofuranoside derivative (9). Further elongation of the glycoside chain might be possible in the same way.     

CHEMOENZYMATIC SYNTHESIS OF NeuAcα-(2→3)-Galβ-(1→3)-[NeuAcα-(2→6)]-GalNAcα1- O-(Z)-Serine (N-PROTECTED MUC II OLIGOSACCHARIDE–SERINE)

An efficient synthesis of NeuAcα-(2→3)-Galβ-(1→3)-[NeuAcα-(2→6)]-GalNAcα1- O-(Z)-Serine (N-protected MUC II oligosaccharide–serine, 14) by a chemoenzymatic strategy is described. The enzymatic reaction of GalNAcα1- O-(Z)-Ser- OAll 7 with pNP-β-Gal in the presence of recombinant β1,3-galactosidase from Bacillus circulans gave Galβ-(1→3)-GalNAcα1- O-(Z)-Ser- OAll 3 in 68%. The introduction of two sialic acids into 3 was accomplished by a stepwise method. The branched Galβ-(1→3)-[NeuAcα-(2→6)]-GalNAcα1- O-(Z)-Ser- OAll 11 was constructed by a chemical method. Sialylation at the C-3 position of the terminal Gal residue on Galβ-(1→3)-[NeuAcα-(2→6)]-GalNAcα1- O-(Z)-Serine 2 using α2,3-(O)-sialyltransferase from rat liver gave a target compound 14 in a practical yield.     

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.     

A Per-O-Isoprofylidene Derivative of (1→4)-β-D-Mannan

Abstract

Isopropylidene acetals of carbohydrates are important as intermediates for the synthesis of other sugar derivatives. The isopropylidenation reaction is generally applied to only low molecular weight carbohydrates. However in 1982, we applied the reaction to a polysaccharide² and demonstrated that (1→3)-β-D-glucan was isopropylidenated at the 4- and 6-hydroxyl groups of the D-glucose units. These results suggested that some chemical modification at the unprotected 2-hydroxyl groups might be possible. Consequently, (1→3)-β-D-glucomannan^3,4 was derived from (1→3)-β-D-glucan through inversion of the 2-hydroxyl groups.     

NMR analysis of conformationally dependent (n)J(C, H) and (n)J(C, C) in the trisaccharide α-L-Rhap-(1 → 2)[α-L-Rhap-(1 → 3)]-α-L-Rhap-OMe and a site-specifically labeled isotopologue thereof

An array of NMR spectroscopy experiments have been carried out to obtain conformationally dependent (1)H,(13)C- and (13)C,(13)C-spin-spin coupling constants in the trisaccharide α-L-Rhap-(1 → 2)[α-L-Rhap-(1 → 3)]-α-L-Rhap-OMe. The trisaccharide was synthesized with (13)C site-specific labeling at C2' and C2″, i.e. in the rhamnosyl groups in order to alleviate (1)H spectral overlap. This facilitated the measurement of a key trans-glycosidic proton-proton cross-relaxation rate using 1D (1)H,(1)H-T-ROESY experiments as well as a (3)J(C, H) coupling employing 1D (1)H,(13)C-long-range experiments, devoid of potential interference from additional J coupling. By means of both the natural abundance compound and the (13)C-labeled sample 2D (1)H,(13)C-J-HMBC and (1)H,(13)C-HSQC-HECADE NMR experiments, total line-shape analysis of (1)H NMR spectra and 1D (13)C NMR experiments were employed to extract (3)J(C, H) , (2)J(C, H), (3)J(C, C), and (1)J(C, C) coupling constants. The (13)C site-specific labeling facilitates straightforward determination of (n)J(C, C) as the splitting of the (13)C natural abundance resonances. This study resulted in eight conformationally dependent coupling constants for the trisaccharide and illustrates the use of (13)C site-specific labeling as a valuable approach that extends the 1D and 2D NMR methods in current use to attain both hetero- and homonuclear spin-spin coupling constants that subsequently can be utilized for conformational analysis.     

Synthesis of (1→5)-β-d-galactofuranan and cyclo[(1→5)-β-d-galactofurano]oligosaccharides

Synthesis of a linear (1→5)-β-d-galactofuranan was accomplished by trityl-cyanoethylidene polycondensation. On 10-fold reduction in the monomer concentration, the condensation products are cyclic oligosaccharides; the formation of 1,5-anhydro-α-d-galactofuranose was also demonstrated.     

α-Hydroxy- and (α-acyloxyimino)benzylphosphonates

N-Hydroxyfluorobenzimidoylphosphonates and their O-acyl derivatives are synthesized. Reaction of phosphorylated oximes with sulfinyl chloride proceeds with rearrangement and leads to synthetically prospective N-sulfonylimidoylphosphonates. By the method of ¹⁹F NMR are revealed values of σ-constants of N-hydroxy- and N-acyloxy substituted imidoylphosphonate groups.     

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.     

Syntheses of P-Nitrophenyl 6-O-α- and 6-O-β-D-Xylopyranosyl-β-D-glucopyranoside

Condensation of p-nitrophenyl 2,3,4-tri-O-benzoyl-β-D-glucopyranoside 3 with 2,3,4-tri-O-(chlorosulfonyl)-β-D-xylopyranosyl chloride by the Koenigs-Knorr method afforded the α-linked product in a high yield. Dechlorosulfation with sodium iodide and debenzoylation by the Zemplen method gave crystalline p-nitrophenyl 6-O-(α-D-xylopyranosyl)-β-D-glucopyranoside 7.

Compound 3 was condensed with 2,3,4-tri-O-benzoyl-α-D-xylopyranosyl bromide in the presence of mercury (II) cyanide in acetonitrile, and after debenzoylation, crystalline p-nitrophenyl 6-O-(β-D-xylopyranosyl)-β-D-glucopyranoside 10 was obtained.     

Synthesis of 4-O-(α-L-Rhamnopyranosyl-D-Glucopyranuronic Acid

Abstract

Two approaches were used for the synthesis of 4-O-(α-l-rhamno-pyranosyl)-d-glucopyranuronic acid (1). Rhamnosylation of benzyl 6-O-allyl-2,3-di-O-benzyl-β-d-glucopyranoside (7), followed by deallylation, oxidation to uronic acid, and deblocking afforded 1. Alternatively, rhamnosylation of suitably protected d-glucuronic acid derivatives (25 and 26) gave the protected pseudoaldoBiouronic acid derivatives (19 and 30), which were deprotected. Rhamnosylations were performed in high stereoselectivity without neighbouring-group assistance using 2,3,4-tri-O-benzyl-1-O-trichloroacetimidoyl-α-l-rharnnopyranose (27) with tri-fluoromethanesulfonic acid catalysis.     

Regioselective lipase acylation as a useful tool for separation and selective protection of β-d-Gal(1→4)-d-GlcNAc and β-d-Gal(1→3)-d-GlcNAc disaccharides

Supported lipase from Candida antarctica (Chirazyme®) was employed for a regioselective protection of the 2-azido derivatives 1 and 2, synthetic equivalents of β-d-Gal(1→3)-d-GlcNAc and β-d-Gal(1→4)-d-GlcNAc (N-acetyl lactosamine), respectively. The selectivity of the enzyme towards 1 and 2 was also exploited for an easy separation of the mixture of the two compounds obtained from a straightforward synthetic approach.     

Synthesis of benzyl O-(2,3,3'-tri-O-acetyl-β-D-apiofuranosyl)-(1→3)-2,4-di-O-benzoyl-α-D-xylopyranoside and its X-ray structure

The protected apiose-containing disaccharide, benzyl O-(2,3, 3'-tri-O-acetyl-β-D-apiofuranosyl)-( 1→3)-2, 4-di-O-benzoyl-α-D-xylopyranoside, was synthesized and its X-ray structure provided.     

Theoretical study of the stability and electronic structure of Al(BH4)n=1→4 and Al(BF4)n=1→4 and their hyperhalogen behavior

Using density functional theory (DFT), we have systematically calculated the equilibrium geometries, electronic structure, and electron detachment energies of Al(BH(4))(n=1→4) and Al(BF(4))(n=1→4) at the B3LYP/6-311+G(2d,p) level of theory. The electron affinities of Al(BH(4))(n) not only exhibit odd-even alternation, just as seen in (BH(4))(n), but also, for n = 3 and 4, show a remarkable behavior: whereas the electron affinities of BH(3) and BH(4) are, respectively, 0.06 and 3.17 eV, those of Al(BH(4))(3) and Al(BH(4))(4) are 0.71 and 5.56 eV. Results where H is replaced by F are also very different. The electron affinities of BF(3) and BF(4) are, respectively, -0.44 and +6.86 eV, and those of Al(BF(4))(3) and Al(BF(4))(4) are 1.82 and 8.86 eV. The results demonstrate not only marked difference when H is replaced by F but also substantially enhanced electron affinities by almost 2 eV when BH(4) and BF(4) units are allowed decorate a metal atom, confirming the recently observed hyperhalogen behavior of superhalogen building blocks.