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 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.     

十二烷基β-D-葡萄吡喃糖基-(1→3)-[β-D-葡萄吡喃糖基-(1→6)]-β-D-葡萄吡喃糖基-(1→6)-β-D-葡萄吡喃糖苷的合成

本文以3-O-烯丙基-6-O-乙酰基-2,4-二-O-苯甲酰基-α-D-葡萄糖三氯乙酰亚氨酯1为原料,设计合成了尚未见报道的十二烷基β-D-葡萄吡喃糖基-(1→3)-[β-D-葡萄吡喃糖基-(1→6)]-β-D-葡萄吡喃糖基-(1→6)-β-D-葡萄吡喃糖苷6。其组成和结构已由元素分析、1H NMR、13C NMR表征。     

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.     

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.     

Synthesis of a (1→6)-β-Linked N-Acetyl-d-glucosamine Oligosaccharide1

Abstract

1,6-Anhydro-2-deoxy-3,4-di-O-benzyl-2-phthalimido-β-d- glucopyranose (5) was synthesized from 1,6-anhydro-β-d-mannopyranose (1) in five steps. Compound 5 was polymerized under cationic conditions and selectively yielded glucosamine oligomers (degree of polymerization 5-7). Copolymerization of 5 with 1,6-anhydro-2,3,4-tri-O-benzyl-β-d-glucopyranose indicated the low reactivity of 5 with the active cation derived from 5. Deprotection of 2-deoxy-3,4-di-O-benzyl-2-phthalimido-(1→6)-β-d-glucopyranan (7) and N-acetylation gave 2-acetamido-2-deoxy-(1→6)-β-d-glucopyranan (9).     

SYNTHESIS OF 3-O-ARABINOSYLATED (1→6)-β-D-GALACTAN EPITOPES

Two tetrameric arabinogalactans, β-D-galactopyranosyl-(1→6)-β-D-galactopyranosyl-(1→6)-[α-L-arabinofuranosyl-(1→3)]-D-galactopyranose (14) and α-L-arabinofuranosyl-(1→3)-β-D-galactopyranosyl-(1→6)-β-D-galactopyranosyl-(1→6)-D-galactopyranose (25), which are good candidates for CCRC-M7 epitope characterization, were synthesized efficiently using a convergent strategy. Migration of an acceptor acetyl group proved to be an obstacle to synthesis, but regioselective glycosylation or 4-O-benzyl protection of the acceptor circumvented this problem allowing efficient synthesis of the 1→6 linked target compounds.     

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.     

Synthesis of ( )-5α-Hydroxy-β-selinene and (-)-5β-Hydroxy-β-selinene

Eudesmanederivativeshavebeendrawingconsiderableattentionduetotheirwidespectrumofbiologicalproperties,particularlyantifeedant,cellgroWthinhibitoryandplantgroWthregulatingactivitiesl'2.Recently,twoepimericeudesmanederivatives( )-5a-hydroxy-6-selinene1and(-)-56-hydroxy-6-selinene2wereisolated3fromtheaerialpartsofCSubtraPicaFMell.,andtheirstructuresweredeterminedbyspectroscopicmethods.Herein,wereportafacilesynthesisofbothtwodiastereomers1and2from( )-dihydrocarvone3infivesteps,usingtheregioselect…     

Synthesis of stigmasteryl (β1→4)-oligoglucosides

Stigmasteryl (β1→4)-oligoglucosides were prepared with cellobiose, cellotriose, and cellotetraose as glycan chains. For the preparation of the peracetylated oligoglucosyl donors anomeric acetate was deprotected and the respective hemiacetals were converted into trichloroacetimidates. Glycosylation with stigmasterol yielded both α- and β-anomers because during the treatment with Lewis acid the 2-OAc is cleaved to some extent; thus, with the emerging hydroxyl group neighboring group participation does not take place. Due to their different number of hydroxyl groups (0 vs. 1) separation of the two products proved to be facile. Saponification led to the desired stigmasteryl glucosides.     

Synthesis of Neu5Ac α-(2→ 8)Neu5Ac α-(2→ 3)Galβ1→ Och2Ch2Ch3, A Determinant Epitope of Gd3 Ganglioside

ABSTRACT

Synthesis of the terminal trisaccharide sequence of the ganglioside GD₃, α-D-Neup5Ac-(2→8)-α-D-Neup5Ac-(2→3)-β-D-Galp-(1→4)-β-D-Glcp-(1→1)-Cer (2) was achieved by employing an α-(2→8) disialyl glycosyl donor (1). Condensation of 1 with the glycosyl acceptor 6, propyl 4,6-O-benzylidene-β-D-galactopyranoside, gave the desired protected trisaccharide 10 (14%) as well as the elimination and hydrolysis products of 6, compounds 8 and 9 respectively. O-Deacetylation and debenzylation of 10 gave the final trisaccharide 11, as its propyl glycoside.     

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.     

Alternative Syntheses of (l→3)-β-D-Galacto-Oligosaccharides

ABSTRACT

Galactosyl halides bearing different substituents at O-3 [i.e. acetyl (15), benzoyl (14), benzyl (3), bromoacetyl (12), and the 2, 3, 4, 6-tetra-O-benzoyl-β-D-galactopyranosyl group (17)] have been prepared, and used to study the stereoselectivity of the coupling reaction to position O-3 of different galactose derivatives [i.e. methyl 2, 4, 6-tri-O-acetyl-(9) and 2, 4, 6-tri-O-benzoyl-β-D-galactopyranoside (7), l, 2, 4, 6-tetra-O-benzoyl-β-D-galactose (6) and O-(2, 4, 6-tri-O-benzoyl-β-D-galactopyranosyl)-(1→3)-β-D-galactose (33)], as well as to benzoic acid. In more polar solvents, using silver trifluoro-methanesulfonate as the promoter, a higher proportion of β-linked products was formed, whereas with silver perchlorate as the promoter the α-linked product predominated. Under basic conditions, applied to prevent anomerisation of 1-O-benzoylated nucleophiles 6 and 33, no orthoesters were found as end products. Under those conditions, a better overall yield of the β-(l→3)-linked galactotriose 31 was obtained by condensation of die disaccharide glycosyl donor 17 and the monosaccharide glycosyl acceptor 6 than by condensation of 14 and 33. The disaccharide glycosyl chloride 17 was obtained in 75% yield by the cleavage of the corresponding methyl glycoside with dichloromethyl methyl ether.     

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.     

麦芽糖基(α-1→6)β-环糊精的酶法合成和结构鉴定

采用地衣芽孢杆菌普鲁蓝酶合成Mal-β-CD, 反应产物体系成分简单, 易于分离, Mal-β-CD的转化率可达到56%.     

β-(1→3)-D-葡聚糖可德胶化学改性的研究进展

可德胶是一种天然的直链型微生物发酵多糖,具有独特的凝胶特性,在食品及医药等领域有重要应用.可德胶不溶于水,这限制了其实际应用.因此对可德胶进行化学改性来扩大其应用范围,成为可德胶研究特别是其生物活性研究的重要方向之一.一些常用的多糖化学改性方法如磺酸化、羧甲基化等已被大量运用于可德胶改性上,这不仅极大改善了可德胶的水溶性,同时也赋予了可德胶更多的生物活性.本文综述了近年来国内外可德胶化学改性的研究进展,着重介绍了可德胶主链水解、磺酸化、羧甲基化、疏水改性等化学修饰的方法和发展动向.同时还介绍了"点击化学"这一最新的选择性化学修饰方法在可德胶化学改性中的应用.     

高圣草素-7-O-β-D-芹糖基(1→2)-β-D-葡萄糖苷与血清白蛋白相互作用研究

在模拟人体生理条件下,应用紫外吸收光谱、荧光光谱和同步荧光光谱法研究高圣草素-7-O-β-D-芹糖基(1→2)-β-D-葡萄糖苷(HAG)与牛血清白蛋白(BSA)及人血清白蛋白(HSA)的结合作用。结果表明:HAG对BSA和HSA的内源荧光均有显著的猝灭作用,且猝灭机理主要为静态猝灭。HAG与BSA和HSA的结合常数K分别为3.03×104L.mol-1和6.22×104L.mol-1,结合位点数n分别为0.858和0.911,结合距离r分别为2.88 nm和3.09 nm,其作用力以氢键和范德华力为主。利用同步荧光技术考察了HAG对BSA和HSA构象的影响。     

具有β-(1→6)-半乳吡喃糖骨架和α-L-(1→3)-阿拉伯呋喃糖侧链的阿拉伯半乳寡糖的简易合成

4-Methoxyphenyl glycoside of β-D-Galp-(1→6)-[α-L-Araf-(1→3)-]β-D-Galp-(1→6)-β-D-Galp-(1→6)-{β-D-Galp-(1→6)-[α-L-Araf-(1→3)-]β-D-Galp-(1→6)-β-D-Galp-(1→6)-}2β-D-Galp-(1→6)-[α-L-Araf-(1→)3)-]β-D-Galp-(1→)6)-β-D-Galp was synthesized with 2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (1), 6-O-acetyl-2,3,4-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (11), 4-methoxyphenyl 3-O-allyl-2,4-tri-O-benzoyl-β-D-galactopyranoside (2),isopropyl 3-O-allyl-2,4-tri-O-benzoyl--thio-β-D-galactopyranoside (12),4-methoxyphenyl 2,3,4-tri-O-benzoyl-β-D-galactopyranoside (5), and 2,3,5-tri-O-benzoyl-α-L-arabinofuranosyl trichloroacetimidate (8) as the key synthons.     

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-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.