Yield of 1,6-anhydro-3,4-dideoxy-β-d-glycero-hex-3-enopyranos-2-ulose (levoglucosenone) on the acid-catalyzed pyrolysis of cellulose and 1,6-anhydro-β-d-glucopyranose (levoglucosan)

Although 1,6-anhydro-3,4-dideoxy-,β-d-glycero-hex-3-enopyranos-2-ulose (2) is produced by the acid-catalyzed pyrolysis of both cellulose and 1,6-anhydro-β-d-glucopyranose (1), data presented here show that the principal mechanism of its formation in the pyrolysis of cellulose is not via 1. Furthermore, the data provide evidence that 1 itself is not a primary product of cellulose pyrolysis, so that the principal mechanism of its formation must involve a precursor as yet unidentified.     

A new chemical synthesis of Ascopyrone P from 1,5-anhydro-D-fructose

The naturally occurring antioxidant Ascopyrone P (1,5-anhydro-4-deoxy-D-glycero-hex-1-en-3-ulose, 1) was prepared from the rare sugar 1,5-anhydro-D-fructose (AF, 3) in three steps in an overall yield of 36%. Thus, acetylation of 3 afforded the enolone 3,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-3-en-2-ulopyranose (4), which could be isomerised to 2,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-1-ene-3-ulose (6). Deacetylation of 6 under mild conditions gave crystalline Ascopyrone P (1).     

Kristall- und molekülstruktur des mono-O-isopropylidenderivatives der dimeren 1,6-anhydro-β-D-arabino-hexopyranos-3-ulose

Acetonation of dimeric 1,6-anhydro-β-D-arabino-hexopyranos-3-ulose yields, besides a monomeric di-O-isopropylidene compound, the dimer 2, which crystallizes in space group P2₁2₁2₁ with a  1.3680 (9), b  1.0686 (7), and c  1.0319 (7) nm, Z  4. The crystal and molecular structure of 2 have been determined by X-ray analysis with direct methods and was refined to a final R_w of 5.55% for 2468 reflections. Compound 2 has not the same dimeric structure as the parent compound with a central 1,4-dioxane ring, but contains instead a central 1,3-dioxolane ring. The pyranose ring bearing the isopropylidene group adopts an almost ideal sofa conformation, with a nearly planar arrangement of C-1, C-2, C-3, C-4, and C-5. By analogy, it was concluded that the dimeric mono-O-isopropylidene derivative 7 of 1,6-anhydro-β-D-xylo-hexopyranos-3-ulose has the same asymmetric structure. The 360-MHz ¹H-n.m.r. spectra of both compounds are in full agreement with the proposed structures.     

Acid-catalyzed pyrolytic synthesis and decomposition of 1,4:3,6-dianhydro-α-d-glucopyranose

1,4:3,6-dianhydro-α-d-glucopyranose (1) was formed, together with 1,6-anhydro-3,4-dideoxy-β-d-glycero-hex-3-enopyranos-2-ulose (levoglycosenone, 2) and levoglucosan (4), on acid-catalyzed pyrolysis of d-glucose, amylopectin, and cellulose. Pyrolysis of 1 in the presence of acid provided significant quantities of 2, indicating that 1 can act as a pyrolytic precursor of 2. A pyrolysis product from cellulose previously considered to be 1,6-anhydro-3-deoxy-β-d-erythro-hex-3-enopyranose (12) was shown to be dianhydride 1.     

Synthesis of 4-cyano- and 4-nitrophenyl 2,5-anhydro- 1,6-dithio-alpha-D-gluco- and -alpha-L-guloseptanosides carrying different substituents at C-3 and C-4

Treatment of 1,6:2,5-dianhydro-3,4-di-O-methanesulfonyl-1-thio-D-glucitol in methanol with sodium hydroxide afforded 1,6:2,5:3,4-trianhydro-1-thio-allitol, 1,4:2,5-dianhydro-6-methoxy-1-thio-D-galactitol, 1,6:2,5-dianhydro-4-O-methyl-1 -thio-D-glucitol, 1 ,6:2,5-dianhydro-3-O-methanesulfonyl-1 -thio-D-glucitol and 1 ,6:2,5-dianhydro-4-deoxy-1-thio-D-erythro-hex-3-ulose (14) in 5, 4, 28, 5.5 and 41% yield, respectively. Formation of these derivatives can be explained via a common sulfonium intermediate. Reduction of 14 with sodium borohydride and subsequent acetylation afforded 3-O-acetyl-1,6:2,5-dianhydro-4-deoxy-1-thio-D-xylo-hexitol, the absolute configuration of which was proved by X-ray crystallography. The 1,6:2,5-dianhydro-1-thio-D-hexitol derivatives in which the free OH groups were protected by acetylation, methylation or mesylation were converted by a Pummerer reaction of their sulfoxides into the corresponding 1-O-acetyl hexoseptanose derivatives which were used as donors for the glycosidation of 4-cyano- and 4-nitrobenzenethiol, respectively. The Pummerer reaction of 1,6:2,5-dianhydro-4-deoxy-3-O-methyl-1-thio-D-xylo-hexitol S-oxide gave, besides 1-O-acetyl-2,5-anhydro-3-deoxy-4-O-methyl-6-thio-alpha-L- (23) and 1-O-acetyl-2,5-anhydro-4-deoxy-3-O-methyl-6-thio-alpha-D-xylo-hexoseptanose (25), 1-O-acetyl-4-deoxy-2,6-thioanhydro-D-lyxo-hexopyranose, formed in a rearrangement reaction. The same rearrangement took place, when a mixture of 23 and 25 was used as donor in the glycosidation reaction with 4-cyanobenzenethiol, applying trimethylsilyl triflate as promoter. The oral antithrombotic activity of the obtained alpha-thioglycosides was determined in rats, using Pescador's model.     

Studies related to the synthesis of derivatives of 2,6-diamino-2,3,4,6-tetradeoxy-D-erythro-hexose (purpurosamine C), a component of gentamicin C12

Reduction of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose (levoglucosenone) with lithium aluminium hydride afforded principally 1,6-anhydro-3,4-dideoxy-β-D-threo-hex-3-enopyranose (3), which was converted into 3,4-dihydro-2(S)-hydroxymethyl-2H-pyran (8) following acid-catalysed methanolysis and reductive rearrangement of the resulting α-glycoside 4 with lithium aluminium hydride. 1,6-Anhydro-3,4-dideoxy-2-O-toluene-p-sulphonyl-β-D-threo-hexopyranose, prepared from 3, reacted slowly with sodium azide in hot dimethyl sulphoxide to give 1,6-anhydro-2-azido-2,3,4-trideoxy-β-D-erythro-hexopyranose, which was transformed into a mixture of methyl 2-acetamido-6-O-acetyl-2,3,4-trideoxy-α-D-erythro-hexopyranoside (10) and the corresponding β anomer following acid-catalysed methanolysis, catalytic reduction, and acetylation. Acid treatment of methyl 4,6-O-benzylidene-3-deoxy-α-D-erythro-hexopyranosid-2-ulose yielded the enone 15, which was readily transformed into methyl 6-O-acetyl-3,4-dideoxy-α-D-glycero-hexopyranosid-2-ulose (19). Procedures for the conversions of DL-8, 10, and 19 into methyl 2,6-diacetamido-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranoside (methyl N,N′-di-acetyl-α-purpurosaminide C) have already been described.     

Enantioseparation properties of (1-->6)-alpha-D-glucopyranan and (1-->6)-alpha-D-mannopyranan tris(phenylcarbamate)s as chiral stationary phases in HPLC

Synthetic polysaccharides, (1-->6)-alpha-D-glucopyranan (3a) and (1-->6)-alpha-D-mannopyranan (3b), were prepared by the cationic ring-opening polymerization of 1,6-anhydro-2,3,4-tri-O-allyl-beta-D-glucopyranose (1a) and 1,6-anhydro-2,3,4-O-6-allyl-beta-D-mannopyranose (1b), followed by the cleavage of the allyl ether linkage of 2,3,4-tri-O-allyl-(1-->6)-alpha-D-glucopyranan (2a) and 2,3,4-tri-O-allyl-(1-->6)-alpha-D-mannopyranan (2b), respectively. 2,3,4-Tris-O-(3,5-dimethylphenylcarbamoyl)- and 2,3,4-tris-O-(3,5-dichlorophenylcarbamoyl)-(1-->6)-alpha-D-glucopyranan (CSP-1 and CSP-2, respectively) and 2,3,4-tris-O-(3,5-dimethylphenylcarbamoyl)- and 2,3,4-tris-O-(3,5-dichlorophenylcarbamoyl)-(1-->6)-alpha-D-mannopyranan (CSP-3 and CSP-4, respectively) were prepared by the reaction of 3 with the corresponding 3,5-disubstituted phenylisocyanates and the chiral recognition abilities of CSP-1-4 as chiral stationary phases (CSPs) in high-performance liquid chromatography (HPLC) were evaluated. Racemic compounds such as trans-cyclopropanedicarboxylic acid dianilide (9), 1,2,2,2-tetraphenylethanol (10), flavanone (11), Tr?ger's base (12), benzoin (13), and cobalt(III) tris(acetylacetonate) (14) were efficiently resolved using CSP-1-4. For comparison among CSPs, the chiral recognition properties of the (1-->6)-alpha-D-glucopyranan CSPs were different from that of the (1-->6)-alpha-D-mannopyranan CSPs, and CSP-4 exhibited the highest chiral recognition ability among the CSPs. The resolution factors of 12 and 14 were 0.42 and 0.56 for CSP-1, 0.32 and 2.16 for CSP-2, 1.80 and 0.84 for CSP-3, and 2.31 and 8.26 for CSP-4, respectively.     

Synthesis of modified tetrasaccharide sequences of N-glycoproteins

The tetrasaccharides O-alpha-D-mannopyranosyl-(1----3)-O-[alpha-D- mannopyranosyl-(1----6)]-O-(4-deoxy-beta-D-lyxo-hexopyranosyl)-(1- ---4)-2- acetamido-2-deoxy-alpha, beta-D-glycopyranose (22) and O-alpha-D-mannopyranosyl-(1----3)-O-[alpha-D-mannopyranosyl-(1----6)]-O- beta-D-talopyranosyl-(1----4)-2-acetamido-2-deoxy-alpha, beta-D- glucopyranose (37), closely related to the tetrasaccharide core structure of N-glycoproteins, were synthesized. Starting with 1,6-anhydro-2,3-di-O-isopropylidene-beta-D-mannopyranose, the glycosyl donors 3,6-di-O-acetyl-2-O-benzyl-2,4-dideoxy-alpha-D-lyxo- hexopyranosyl bromide (10) and 3,6-di-O-acetyl-2,4-di-O-benzyl-alpha-D-talopyranosyl bromide (30), were obtained in good yield. Coupling of 10 or 30 with 1,6-anhydro-2-azido-3-O-benzyl-beta-D-glucopyranose to give, respectively, the disaccharides 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(3,6-di-O-acetyl-2-O-benzyl-4 -deoxy- beta-D-lyxo-hexopyranosyl)-beta-D-glucopyranose and 1,6-anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-(3,6-di-O-acetyl-2,4-di-O-ben zyl- beta-D-talopyranosyl)-beta-D-glucopyranose was achieved with good selectivity by catalysis with silver silicate. Simultaneous glycosylation of OH-3' and OH-6' of the respective disaccharides with 2-O-acetyl-3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl chloride yielded tetrasaccharide derivatives, which were deblocked into the desired tetrasaccharides 22 and 37.     

A facile approach to anhydrogalactosucrose derivatives from chlorinated sucrose

Three new anhydrosucrose derivatives: 1,4:3,6-dianhydro-beta-D-fructofuranosyl 4-chloro-4-deoxy-alpha-D-galactopyranoside (4), 1,4:3,6-dianhydro-beta-D-fructofuranosyl 3,6-anhydro-4-chloro-4-deoxy-alpha-D-galactopyranoside (6) and 1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl-3,6-anhydro-4-chloro-4-deoxy-alpha-D-galactopyranoside (8) were prepared from chlorinated sucrose. The structures of these anhydrides were confirmed by their (1)H and (13)C NMR spectra, ESIMS and elemental analysis. The crystal structures of 6 and the acetate of 4 (5) are presented. The relative reactivity of the chloromethyl groups towards S(N)2 reactions in 1,6-dichloro-1,6-dideoxy-beta-d-fructofuranosyl 4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside was found to be in order 6>6'>1'.     

Synthesis of 4-substituted phenyl 2,5-anhydro-1,6-dithio-alpha-D-gluco- and -alpha-L-guloseptanosides possessing antithrombotic activity

Two independent approaches were investigated for the synthesis of 3,4-di-O-acetyl-1,6:2,5-dianhydro-1-thio-D-glucitol (18), a key intermediate in the synthesis of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-alpha-D-glucoseptanose (13), needed as glycosyl donor. In the first approach 1,6-dibromo-1,6-dideoxy-D-mannitol was used as starting material and was converted via 2,5-anhydro-1,6-dibromo-1,6-dideoxy-4-O-methanesulfonyl-3-O-tetrahydropy ranyl-D-glucitol into 18. The second approach started from 1,2:5,6-di-O-isopropylidene-D-mannitol and the allyl, 4-methoxybenzyl as well as the methoxyethoxymethyl groups were used, respectively, for the protection of the 3,4-OH groups. The resulting intermediates were converted via their 1,2:5,6-dianhydro derivatives into the corresponding 3,4-O-protected 2,5-anhydro-6-bromo-6-deoxy-D-glucitol derivatives. The 1,6-thioanhydro bridge was introduced into these compounds by exchanging the bromine with thioacetate, activating OH-1 by mesylation and treating these esters with sodium methoxide. Among these approaches, the 4-methoxybenzyl protection proved to be the most suitable for a large scale preparation of 18. Pummerer rearrangement of the sulfoxide, obtained via oxidation of 18 gave a 1:9 mixture of 1,3,4-tri-O-acetyl-2,5-anhydro-6-thio-alpha-L-gulo- (12) and -D-glucoseptanose 13. When 12 or 13 were used as donors and trimethylsilyl triflate as promoter for the glycosylation of 4-cyanobenzenethiol, a mixture of 4-cyanophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-alpha-L-gulo- (58) and -alpha-D-glucoseptanoside (61) was formed suggesting an isomerisation of the heteroallylic system of the intermediate. A similar mixture of 58 and 61 resulted when 18 was treated with N-chloro succinimide and the mixture of chlorides was used in the presence of zinc oxide for the condensation with 4-cyanobenzenethiol. When 4-nitrobenzenethiol was applied as aglycon and boron trifluoride etherate as promoter, a mixture of 4-nitrophenyl 3,4-di-O-acetyl-2,5-anhydro-1,6-dithio-alpha-L-gulo- (60) and -alpha-D-glucoseptanoside (62) was obtained. Deacetylation of 58, 61 and 62 according to Zemplen afforded 4-cyanophenyl 2,5-anhydro-1,6-dithio-alpha-L-glucoseptanoside (59), 4-cyanophenyl 2,5-anhydro-1,6-dithio-alpha-D-glucoseptanoside (63) and 4-nitrophenyl 2,5-anhydro-1,6-dithio-alpha-D-glucoseptanoside (66), respectively. The 4-cyano group of 63 was transformed into the 4-aminothiocarbonyl, and the 4-(methylthio)(imino)methyl derivative and the 4-nitro group of 66 into the acetamido derivative. All of these thioglycosides displayed a stronger oral antithrombotic effect in rats compared with beciparcil, used as reference.     

Synthesis, characterization, and lectin recognition of hyperbranched polysaccharide obtained from 1,6-anhydro-D-hexofuranose

1,6-Anhydro-D-hexofuranoses, such as 1,6-anhydro-β-D-glucofuranose (1), 1,6-anhydro-β-D-mannofuranose (2), and 1,6-anhydro-α-D-galactofuranose (3), were polymerized using a thermally induced cationic catalyst in dry propylene carbonate to afford hyperbranched polysaccharides (poly1-3) with degrees of branching from 0.40 to 0.46. The weight-average molecular weights of poly1-3 measured by multiangle laser light scattering varied in the range from (1.02 to 5.84) × 10(4) g·mol(-1), which were significantly higher than those measured by size exclusion chromatography. The intrinsic viscosities ([η]) of poly1-3 were very low in the range from 4.9 to 7.4 mL·g(-1). The exponent (α) in the Mark-Houkwink-Sakurada equation ([η] = KM(α)) of the polymers was 0.20 to 0.33, which is <0.5. The steady shear flow of poly1-3 in an aqueous solution exhibited a Newtonian behavior with steady shear viscosities independent of the shear rate. These viscosity characteristics were attributed to the spherical structures of hyperbranched polysaccharides in an aqueous solution. Poly1-3 contained a high portion of terminal units of 31-43 mol % nonreducing D-hexopyranosyl and D-hexofuranosyl units, in which the D-hexofuranosyl units were 20-44 mol %. Moreover, poly1 and poly2 showed a strong interaction to Concanavalin A due to the cluster effect or multivalent effect of numerous nonreducing saccharide units on their surfaces with binding constants in the range from 1.7 × 10(4) to 2.7 × 10(5) M(-1).     

1,5-Anhydro-4-deoxy-d-glycero-hex-1-en-3-ulose and other pyrolysis products of cellulose

Uncatalyzed pyrolysis of cellulose provides a tar containing mainly 1,6-anhydro-d-glucose derivatives and some unsaturated products. The latter include a new enone that has been isolated by preparative column chromatography in 1.4% yield and identified as 1,5-anhydro-4-deoxy-d-glycero-hex-l-en-3-ulose. This compound is also formed by pyrolysis of other carbohydrate polymers. A mechanism for its production from internal units has been deduced from the experimental data. The pyrolysis products of cellulose also contain 3,5-dihydroxy-2-methyl-4H-pyran-4-one, which appears to be an oxidation product.     

Synthesis and co-polymerization of an unsaturated 1,5-anhydro-D-fructose derivative

An unsaturated derivative, 3,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-3-enopyranos-2-ulose (3), was obtained via regioselective elimination and acetylation of monohydrated 1,5-anhydro-D-fructose (1) in a single step reaction. High yield (80%) was achieved without any dimeric by-products. Its co-polymerization to saccharide polymers was investigated with different commercial vinyl co-monomers. Co-polymers were obtained and characterized.     

Studies on dextranases. 3. Insolubilization of a bacterial dextranase

Ammonium hydroxide treatment of 1,6:2,3-dianhydro-4-O-benzyl-β-D-mannopyranose, followed by acetylation, gave 2-acetamido-3-O-acetyl-1,6-anhydro-4-O-benzyl-2-deoxy-β-D-glucopyranose which was catalytically reduced to give 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose (6), the starting material for the synthesis of (1→4)-linked disaccharides bearing a 2-acetamido-2-deoxy-D-glucopyranose reducing residue. Selective benzylation of 2-acetamido-1,6-anhydro-2-deoxy-β-D-glucopyranose gave a mixture of the 3,4-di-O-benzyl derivative and the two mono-O-benzyl derivatives, the 4-O-benzyl being preponderant. The latter derivative was acetylated, to give a compound identical with that just described. For the purpose of comparison, 2-acetamido-4-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose has been prepared by selective acetylation of 2-acetamido-1,6-anhydro-2-deoxy-β-D-glucopyranose.Condensation between 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide and 6 gave, after acetolysis of the anhydro ring, the peracetylated derivative (17) of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose. A condensation of 6 with 3,4,6-tri-O-acetyl-2-deoxy-2-diphenoxyphosphorylamino-α-D-glucopyranosyl bromide likewise gave, after catalytic hydrogenation, acetylation, and acetolysis, the peracylated derivative (21) of di-N-acetylchitobiose.     

Nitrous acid deamination of conformationally inverted aminodeoxyhexopyranoses

Nitrous acid deamination of 2-amino-1,6-anhydro-2-deoxy-β-D-glucopyranose (1) in the presence of weakly acidic, cation-exchange resin gave 1,6:2,3-dianhydro-β-D-mannopyranose (3) and 2,6-anhydro-D-mannose (6), characterized, respectively, as the 4-acetate of 3 and the per-O-acetylated reduction product of 6, namely 2,3,4,6- tetra-O-acetyl-1,5-anhydro-D-mannitol, obtained in the ratio of 7:13. Comparative deaminatior of the 4-O-benzyl derivative of 1 led to similar qualitative results. Deamination of 3-amino-1,6-anhydro-3-deoxy-β-D-glucopyranose gave 1,6:2,3- and 1,6:3,4-dianhydro-β-D-allopyranose (13 and 16), characterized as the corresponding acetates, obtained in the ratio of 31:69, as well as the corresponding p-toluenesulfonates. Deamination of 4-amino-1,6-anhydro-4-deoxy-β-D-glucopyranose and of its 2-O-benzyl derivative gave the corresponding 1,6:3,4-D-galacto dianhydrides as the only detectable products. 2,5-Anhydro-D-glucose, characterized as the 1,3,4,6-tetra-O- acetyl derivative of the corresponding anhydropolyol, was obtained in 39% yield from the same deamination reaction performed on 2-amino-1,6-anhydro-2-deoxy-β-D- mannopyranose (24). In 90% acetic acid, the nitrous acid deamination of 24, followed by per-O-acetylation, gave only 1,3-4-tri-O-acetyl-2,5-anhydro-α-D-glucoseptanose. In the case of 1,6-anhydro-3,4-dideoxy-3,4-epimino-β-D-altropyranose, only the corresponding glycosene was formed, namely, 1,6-anhydro-3,4-dideoxy-β-D-threo--hex-3-enopyranose.     

Synthesis of 8-(hydroxyalkyl)adenines

Treatment of methyl 4,6-O-benzylidene-2-O-p-tolylsulfonyl-α-D-ribo-hexopyranosid-3-ulose (1) with triethylamine-methanol at reflux temperature yields methyl 2,3-anhydro-4,6-O-benzylidene-3-methoxy-α-D-allopyranoside (2), a derivative (3) of 3-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one, and methyl 4,6-O-benzylidene-α-D-ribo-hexopyranosid-3-ulose dimethyl acetal (4). The reaction of methyl 4,6-O benzylidene-3-O-p-tolylsulfonyl-α-D-arabino-hexopyranosid-2-ulose (12) with triethylamine-methanol afforded methyl 4,6-O-benzylidene-α-D-ribo-hexopyranosid-2-ulose dimethyl acetal (19) and methyl 2,3-anhydro-4,6-O-benzylidene-2-methoxy-α-D-allopyranoside (20); from the reaction of the β-D anomer (13) of 12, methyl 4,6-O-benzylidene-β-D-ribo-hexopyranosid-2-ulose dimethyl acetal (21) was isolated. Syntheses of the α-keto toluene-p-sulfonates 12 and 13 are described. Mechanisms for the formation of the compounds isolated from the reactions with triethylamine-methanol are proposed.     

Selective protections on 2-allyloxycarbonylamino-1,6-anhydro-2-deoxy-beta-D-glucopyranose.

Regioselective monoacetylation of 2-allyloxycarbonylamino-1,6-anhydro-2-deoxy-beta-D-glucopyranose (1) gave a mixture of 3-O-acetyl and 4-O-acetyl derivatives, the structures of which were established by two-dimensional, phase-sensitive NOESY and confirmed by chemical proofs. The benzylation of 1, on the other hand, led to 2-allyloxycarbonylamino-1,6-anhydro-3,4-di- (5) or 2-allyloxycarbonylamino-1,6-anhydro-2-N-benzyl-3,4-di-O-benzyl-2-d eoxy-beta-D- glucopyranose (10). The regioselective cleavage of 5 with titanium tetrachloride gave the expected 3-O-benzyl derivative, the structure of which was ascertained by chemical proofs; the same reaction performed on 10 led to the opening of the anhydro ring to afford 3-benzyl-[3,4-di-O-benzyl-1,2-dideoxy-alpha-D-glucopyrano]-[2,1-d] -2- oxazolidone.     

Synthesis, from cellobiose, of a trisaccharide closely related to the GlcNAc----GlcA----GlcN segment of the antithrombin-binding sequence of heparin

O-(2-Deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)- O-(beta-D- glucopyranosyluronic acid)-(1----4)-1,6-anhydro-2-deoxy-2-sulfamido-6-O-sulfo-beta-D-gl ucopyranose pentasodium salt (14) was synthesized as a heparin-related oligosaccharide. The glycosyl acceptor (derived from cellobiose) and a glycosyl donor, 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide, were coupled in the presence of mercuric bromide and molecular sieves 4A to afford a 69% yield of fully protected trisaccharide, namely, O-(6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1 ----4)- O-(methyl 2,3-di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-3-O-acetyl- 1,6-anhydro-2 - azido-2-deoxy-beta-D-glucopyranose (10), which was converted into the partially sulfated trisaccharide 14. Compound 10 also underwent acetolysis to afford the glycosyl acetate, for further elongation of the glycosyl chain.     

Glycosidation of 2,5-anhydro-3,4-di-O-benzyl-D-mannitol with different glucopyranosyl donors: a comparative study

2,5-Anhydro-3,4-di-O-benzyl-D-mannitol was glycosylated using different donors such as tetra-O-acetyl-alpha-D-glucopyranosyl bromide in the presence of Hg(CN)(2), the corresponding beta-thiophenylglycoside in the presence of NIS and TfOH as well as the alpha- and beta-trichloroimidate with TMSOTf as promoter. The resulting mixtures were analyzed by HPLC and the following main components were isolated and characterized: 2,5-anhydro-3,4-di-O-benzyl-1-O-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-d-mannitol; 6-O-acetyl-2,5-anhydro-3,4-di-O-benzyl-1-O-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-D-mannitol; 2,5-anhydro-3,4-di-O-benzyl-1,6-bis-O-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-D-mannitol; 2,5-anhydro-3,4-di-O-benzyl-1-O-[-2-O-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-3,4,6-tri-O-acetyl-beta-D-glucopyranosyl]-6-O-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-D-mannitol and 2,5-anhydro-3,4-di-O-benzyl-1,6-bis-O-(3,4,6-tri-O-acetyl-1,2-O-ethylidene-2'-yl-alpha-D-glucopyranosyl)-D-mannitol. The latter compound representing a bis-orthoester might be a common intermediate in all the investigated reactions, as its rearrangement and/or decomposition can yield all of the isolated compounds.     

Regio- and stereoselective cyclizations of dianhydro sugar alcohols catalyzed by a chiral (salen)Co(III) complex

The (salen)Co(III)OAc ((R,R)-1 and (S,S)-1) catalyzed cyclizations of the chiral dianhydro sugars, 1,2:5,6-dianhydro-3,4-di-O-methyl-D-glucitol (2), 1,2:5,6-dianhydro-3,4-di-O-methyl-D-mannitol (3), 1,2:5,6-dianhydro-3,4-di-O-methyl-L-iditol (4), and 1,2:4,5-dianhydro-3-O-methyl-L-arabinitol (5), is a facile method for the synthesis of anhydroalditol alcohols. Cyclization of 2 using (R,R)-1 and (S,S)-1 proceeded diastereoselectively to form 2,5-anhydro-3,4-di-O-methyl-D-mannitol (6) and 2,5-anhydro-3,4-di-O-methyl-L-iditol (7), respectively. The cyclization of 3 and 5 is a novel method for obtaining 1,6-anhydro-3,4-di-O-methyl-D-mannitol (11) and a stereoselective route to 1,5-anhydro-3-O-methyl-L-arabinitol (13). It is proposed that the reaction occurs via endo-selective cyclization of an epoxy alcohol produced by the endo-selective ring-opening of one of the two epoxide moieties in the starting material.