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Stereo- and regioselective formation of glycosidic linkages is a challenging topic in oligosaccharide syntheses. The stereoselective construction of 1,2-trans-glycosides generally involves neighboring group participation, which is less successful when synthesizing β-1,3-linked oligosaccharides. The combined steric effect of a 2-O-substituent and an aglycon moiety in acceptors increases the efficiency of glycosylation via neighboring group participation. This steric effect was reduced by using vicinal polyol acceptors and was demonstrated in the synthesis of 1,3-linked branched oligosaccharides.

LETTER, Oligosaccharide containing macrolides of resin glycosides were effectively constructed by MeOTf promoted intramolecular glycosylation of dodecyl thioglycosyl donors. Synthesis of a key disaccharide intermediate of tricolorin A and total synthesis of tricolorin F were successfully achieved by this approach.

The first total synthesis of a unique tetrasaccharide repeating unit of lipopolysaccharide from Salmonella enteritidis has been accomplished by assembly of dodecyl thioglycosides. The crucial key steps were preparation of a rare branched dideoxy sugar, d -tyvelose (3,6-dideoxy- d -arabino- d -hexose) and sequential regioselective glycosylation at 2,3-positions of a central d -mannose residue 5 with d -tyvelose 6 and d -galactose donors 7.

A novel approach to natural β-hydroxy-γ-lactone 2 from 2,5-anhydro- d -mannitol ( 1 ) is described. The key reactions in this synthesis include stereoselective methylation of aldehyde 3 with lithium dimethylcuprate, an intramolecular radical cyclization of seleno carbonate 11 and an intermolecular cross-metathesis of 3-allyl-4-hydroxy-γ-lactone 16 with 1-tridecene.

An efficient and practical method for the large-scale synthesis of an anti-inflammatory glycocluster having seven sialyl Lewis X (SLeX) residues was established on the basis of chemical and enzymatic strategy from β-cyclodextrin (β-CD) as a key starting scaffold material. A key intermediate, β-CD derivative having seven N-acetyl- d -glucosamine (GlcNAc) residues [(GlcNAc)7CD], was prepared by a coupling reaction with heptakis 6-deoxy-6-iodo-β-cyclodextrin and sodium thiolate containing a GlcNAc residue. Subsequent sugar elongation reactions of (GlcNAc)7CD proceeded smoothly by means of β-1,4-galactosyltransferase, α-2,3-sialyltransferase, and α-1,3-fucosyltransferase V in the presence of the corresponding sugar nucleotides (UDP-Gal, CMP-Neu5Ac, and GDP-Fuc) and allowed to give a mono-dispersed glycodendrimer (Mw=7924.5, calcd for C301H490N21O196S7Na7; MALDI-TOF MS, m/z 7946 [M+Na]+) that completely substituted with seven SLeX branches at C-6 positions in excellent overall yield (74%, 3 steps). Hyper-branched glycodendrimer, (SLeX)7CD, exhibited highly amplified inhibitory effect on the interaction of E-selectin with SLeXn-BSA immobilized on the sensor chip by means of surface plasmon resonance method.

Calonyctin A2, a tetrasaccharidic glycolipid having a 22-membered macrolidic structure, has been synthesized by the assembly of three 6-deoxygenated thioglycoside intermediates. The short-step synthesis was achieved by preparation of the most complicated b–c disaccharide unit from phenyl 2,2′:4,6:4′,6′-tri-O-benzylidene-1-thio-β- d -laminaribioside without any glycosidation reaction and by regioselective macrolactonization.

A (+)-10-Camphorsulfonic acid-catalysed acetal exchange reaction of phenyl 1-thio-β-laminaribioside using 3.5 molar equivalents of α,α-dimethoxytoluene gave a tris(benzylidene acetal), which was isolated and characterized as phenyl 3′-O-acetyl-2,2′ : 4,6 : 4′,6′-tri-O-benzylidene-1-thio-β-laminaribioside, and the corresponding 3′-O-benzyl derivative 6. Upon a treatment with pyridinium p-toluenesulfonate, the interglycosidic 2,2′-acetal in 6 underwent selective cleavage to give the 2,2′-diol. Additionally, a reductive ring-opening reaction of 6 with lithium aluminium hydride/anhydrous aluminium chloride, followed by O-acetylation, gave the 2,6,6′-O-acetyl-4,2′,3′,4′-tetra-O-benzyl derivative in 73% yield. A different regioselectivity was observed in the reduction of 6 with borane-trimethylamine adduct/anhydrous aluminium chloride or sodium cyanotrihydroborate/methanesulfonic acid, giving the corresponding 2,4,4′-triol as the major product.

A novel polysaccharide having a N-acetylglucosamine (GlcNAc) residue as one of the constituents was synthesized by incubation of Acetobacter xylinum in a modified Schramm-Hestrin medium containing lysozyme-susceptible phosphoryl chitin (P-chitin) andd-glucose. HPLC of the culture medium snowed that the P-chitin added was depolymerized to monomeric and oligomeric P-chitins during the incubation, and the P-chitins with permeable sizes were utilized as a carbon source by the bacteria.13C NMR analysis revealed that the P-chitin consists mainly of GlcNAc 6-P residues. Furthermore, monomeric GlcNAc 6-phosphate was also found to enhance the incorporation of GlcNAc residues into the polysaccharide. However, no incorporation of the GlcNAc residues was observed when A. xylinum was incubated in a medium containing either highly phosphorylated chitin (DS = 1.90) or its oligomers produced by acid hydrolysis.

2-Amino-2-deoxy-cyclomaltoheptaose was prepared from β-cyclodextrin perbenzoate [heptakis(2,3,6-tri-O-benzoyl)cyclomaltoheptaose] by a series of reactions including selective de-O-benzoylation at C-2 of one of the perbenzoylated d -glucopyranosyl moieties, oxidation to the 2-ulose derivative, oxime formation, and reduction to the 2-amino-2-deoxy- d -glucose moiety. This compound and 6-amino-6-deoxycyclomaltoheptaose accessible from β-cyclodextrin through the known procedure were sulfated to give polysulfated aminocyclomaltoheptaose derivatives (3, 5). Employing β-cyclodextrin polysulfate as a reference compound, the synergistic effects of 3 and 5 for cortexolone on angiogenesis inhibitory activity were examined by rabbit-corneal micropocket assay system. In contrast to the significant anti-angiogenesis activity of the β-cyclodextrin polysulfate-cortexolone pair, neither 3 nor 5 showed any cooperative activity with cortexolone in the inhibition of basic FGF-induced angiogenesis.

The synthesis of the title compound and 1 d -(1,3,5/2,4)-4-acetamido-5-amino -3-O-(β- d -glucopyranosyluronic acid)-1,2,3-cyclohexanetriol is described. Starting from methyl 2-acetamido-2-deoxy-α- d -glucopyranoside 2 l -(2,4,5/3)-4-acetamido-3-benzoyloxy-2-benzyloxy-5-hydroxycyclohexanone was prepared via a series of transformations including the regioselective ring opening of the benzylidene acetal and the mercury(II)-catalyzed carbocyclic ring closure reaction of 5-enopyranoside. Stereoselective reduction of ketone 11 with NaBH(OAc) 3 gave 1 d -(1,2,4/3,5)-2-acetamido -3-O- benzoyl -4-O- benzyl-1,3,4,5-cyclohexanetetrol (88%), which was then converted into 1 d -(1,3,5/2,4)-4-acetamido-5-azido -3-O- benzoyl -2-O- benzyl -1-O- pivaloyl-1,2,3-cyclohexanetriol through selective 5-OH protection, 1- O -mesylation, and subsequent azide displacement. Saponification and hydrogenation of this gave the title compound. Selective O -debenzoylation with 1.1 equiv of K 2 CO 3 in MeOH gave 1 d -(1,3,5/2,4)-4-acetamido-5-azido -2-O- benzyl -1-O- pivaloyl-1,2,3-cyclohexanetriol (73%). Glycosylation of this compound with methyl (2,3,4- tri -O- acetyl-α- d -glucopyranosyl bromide)uronate in CH 2 Cl 2 , using silver triflate as the promoter, afforded 1 d -(1,3,5/2,4)-4-acetamido-5-azido -2-O- benzyl -3-O-( methyl 2,3,4-tri -O- acetyl-β- d -glucopyranosyluronate )-1-O- pivaloyl-1,2,3-cyclohexanetriol ( 20 ) in 79% yield. Finally, O -deacylation and subsequent hydrogenation of this compound gave the basic pseudo-disaccharide.

Acetolysis of fully acetylated α-cyclodextrin 5a resulted in restricted fission of only one of the glycosidic bonds to give the acyclic maltohexaose peracetate 6a in 46% yield. Regioselective modifications of both terminals of hexasaccharide 6a were performed by employing Lewis acid-catalysed thioglycosidation and O-benzylidenation followed by its reductive cleavage as the key reactions, to give the partially O-benzylated maltohexaoside 9a with the sole hydroxy group at the 4VI-position. Coupling of compound 9a and a D-glucosamine precursor by the trichloroacetimidate method gave the heptasaccharide 15, subsequent deprotection of which gave 2-amino-2-deoxy-β-cyclodextrin 1.

2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-D-allopyranose, needed as one of the building blocks for construction of a novel cyclodextrin-like compound, was prepared in the form of crystalline β-anomer 6 from methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-D-allopyranoside 1. As a model of α-glycosidation necessary for formation of a cyclic structure, 6 was converted into the corresponding β-glycosyl trichloroacetimidate and coupled with methyl 6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside 8, giving α(1→4)-linked disaccharide derivative 9.

An efficient procedure for modification at C-2 position of fully methylated α-, β-, and γ-cyclodextrins was achieved by thiolytic fission of one of their glycosidic bonds, followed by conversion of the resulting 1-thioglycosides into glycals and addition of iodonium ion accompanied intramolecular glycosidation, giving novel methylated cyclooligosaccharides containing 2-deoxy-2-iodo-α-D-mannopyranosyl moiety as one of the constituents.

The synthesis of β-(1→3)-linked galactobiose octaacetate (14) was achieved in a 6-step reaction sequence in more than 30% overall yield, starting from the readily available laminaribiose octaacetate (2). The key steps in this synthesis involved the efficient transformation of 4,6:4′,6′-di-O-benzylidene derivative (5) into the diol (6) through regioselective reductive ring opening of the two benzylidene acetals, the preparation of the corresponding ditriflate (12) and dimesylate (8), and their subsequent SN2 displacement by benzoate and/or thiolacetate anion to give the β-(1→3)-linked Gal-Gal disacharide derivative (10) and related thio compounds 11 and 13. The big difference of the reactivities between the two mesyloxyl groups of 8 enabled their replacement with different nucleophiles.

1,6-Anhydro derivatives of D-glucopyranose, maltose, and maltotriose reacted at room temperature with trimethylsilylated benzenethiol (2) and cyclohexanethiol (3) in the presence of zinc iodide (Znl2) or trimethylsilyl triflate (TMSOTf), giving the corresponding thioglycosides with predominance of one anomer in high yield. 1,6-Anhydro-2,3,4-tri-O-benzyl-β-D-glucopyranose (1) condensed with a more complex thiol derivative, methyl 2,3,6-tri-O-benzyl-4-thio-4-S-trimethylsilyl-α-D-glucopyranoside (19), to give the 4-thiomaltose derivative (20), whereas no condensation took place between the 1,6-anhydro disaccharide homologue (21) and thiol derivative (19). The difference in reactivity between 1,6-anhydro mono- and di-saccharides was utilized for a specific cross-coupling reaction.

Thioacetolysis of per-O-benzylated and per-O-acetylated derivatives of 1,6-anhydro-β-D-glucopyranose (1 and 3) with acetyl sulfide using acidic catalysts gave α- and β-anomers of 1-S-acetyl-1-thio-D- glucopyranose, respectively. The formation of the β-anomer from 3 was in contrast to the predominance of the α-anomer as the product of the usual acetolysis of 3. Similar thioacetolysis of per-O-benzylated 1,6-anhydro-maltose (5) under optimized conditions resulted in opening of the 1,6-anhydro ring and simultaneous removal of the C-6′ benzyl group without cleavage of the internal glycosidic linkage, giving the 6,6′-di-O-acetyl-1-S-acetyl-α-thio-maltose derivative (6) in moderate yield.

An allopyranosyl analog of allyl N,N′-diacetylchitobioside was converted to the corresponding N,N′-diphthaloylated glycosyl acetate in good yield. A thioglycosidation reaction of the glycosyl acetate gave phenyl 3,6-di-O-acetyl-4-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-allopyranosyl)-2-deoxy-2-phthalimido-1-thio-β-D-allopyranoside, the key intermediate employed in the total synthesis of an insect chitinase inhibitor, allosamidin.

A 2′,6′-diamino-1,6-anhydro disaccharide derivative (6) was prepared from maltose. The 3′,4′-diol system of 6 was successfully converted into the 3′-ene system by application of the Corey–Winter procedure, giving the hex-3′-enopyranose derivative (8). Catalytic hydrogenation of 8 gave the dideoxy derivative, a key intermediate for the synthesis of a new aminoglycoside.

Transacetalation of fully 6- O -pivaloylated α-, β-, and γ-cyclodextrins with benzaldehyde dimethylacetal in the presence of (+)-10-camphorsulfonic acid gave monobenzylidene acetals ( 4, 5, 6 ) in moderately good yields. Benzylation of the β-cyclodextrin derivative 5 followed by acid-catalyzed hydrolysis of the benzylidene group and acetylation afforded a di- O -acetyl-non-adeca- O -benzyl derivative 9 . NMR spectroscopic analysis of 9 , including two-dimensional HOHAHA and 1 H 13 C correlation experiments revealed that the benzylidene group bridged the O-2 and O-3 positions of contiguous d -glucopyranosyl residues. Reductive ring-opening of the benzylidene acetal with lithium aluminum hydride/aluminum chloride afforded predominantly a 2 1 - O -unprotected derivative 10 in good yield.

6-Amino-6-deoxychitosan was prepared from 6-deoxy-6-halo-N-phthaloylchitosan via 6-azidation. The product has high stereoregularity because of the effective and regioselective reactions. To evaluat...

N-phthaloylchitosan with high structural regularity found to be a good substrate for nucleophilic substitution with N-halosuccinimides and triphenylphosphine in N-methyl-2-pyrrolidone, which provided the corresponding 6-deoxyhalogenated derivatives in a highly regioselective manner.

A 2′,6′-diamino-1,6-anhydro disaccharide derivative (6) was prepared from maltose. The 3′,4′-diol system of 6 was successfully converted into the 3′-ene system by application of the Corey–Winter procedure, giving the hex-3′-enopyranose derivative (8). Catalytic hydrogenation of 8 gave the dideoxy derivative, a key intermediate for the synthesis of a new aminoglycoside.

New antimicrobial aminoglycosides having a pseudodisaccharide structure, 1L-(1,6/2,3)-3-amino-2-(2,6-diamino-2,6-dideoxy-α-D-allopyranosyloxy)-6-[glycyl(methyl)amino]cyclohexanol (4) and its 3′-deoxy analogue (5) have been synthesized from 1,6-anhydro-β-maltose (6), utilizing its internal glycosidic linkage. This synthesis involves regio- and stereo-selective introduction of amino precursors, azido and methylamino groups, and transformation of the 1,6-anhydrohexopyranose moiety into a cyclitol moiety. The latter was accomplished by application of novel chemical devices, such as formation of phenyl 1-thioglycosides (32) and (39) by selective fission of 1,6-anhydro rings of disaccharides, and application of Ferrier's carbocyclization reaction to the thioglycosides.

Efficient conversion of α-cyclodextrin peracetate 2 into icosa-O-acetylmaltohexaose 3 by acetolytic fission of one glycosidic linkage, a series of manipulations including coupling with a 2-azido-2-deoxy-D-glucopyranose derivative, recyclization and final work-up (catalytic hydrogenolysis etc.) gave a novel β-cyclodextrin analogue 10 containing a D-glucosamine residue as a monosaccharide component.

Iodonium ion treatment of 1,2-unsaturated octa-O-methylmaltotriose having a sole hydroxy group at the 4″-position results in dimerization of the trisaccharide derivative with simultaneous cyclization, giving a fully methylated cyclohexasaccharide consisting of four α-D-glucopyranosyl residues and two 2-deoxy-2-iodo-α-D-mannopyranosyl residues.

New antimicrobial aminoglycosides having a pseudodisaccharide structure, 1L-(1,6/2,3)-3-amino-2-(2,6-diamino-2,6-dideoxy-α-D-allopyranosyloxy)-6-[glycyl(methyl)amino]cyclohexanol (4) and its 3′-deoxy analogue (5) have been synthesized from 1,6-anhydro-β-maltose (6), utilizing its internal glycosidic linkage. This synthesis involves regio- and stereo-selective introduction of amino precursors, azido and methylamino groups, and transformation of the 1,6-anhydrohexopyranose moiety into a cyclitol moiety. The latter was accomplished by application of novel chemical devices, such as formation of phenyl 1-thioglycosides (32) and (39) by selective fission of 1,6-anhydro rings of disaccharides, and application of Ferrier's carbocyclization reaction to the thioglycosides.

Penta-N,O-acetylvaliolamine (11), a derivative of microbial α-D-glucosidase inhibitor, was prepared from the chiral azido-containing cyclohexene derivative derived from D-glucose. Novel rearrangement of the C-C double bond accompanying reduction of the azido group vas a key step for the preparation.

The basic pseudotrisaccharide ( 1 constituting the common and essential building block of several α-glucosidase inhibitors of microbial origin was synthesized by coupling two synthons: the chiral cyclohexyl halide ( 11 ) and the 4′-amino-4′-deoxy-disaccharide ( 14 ).

1 d -(1,2,4/3)-2,3,4-Tri- O -benzyl-5-(trityloxymethyl)-5-cyclohexene-1,2,3,4-tetrol ( 5a ) and its 1 l -(1,3/2,4) isomer ( 5b ) were prepared from d -glucose, and they underwent ready mutual interconversion through an S N 2 procedure employing a benzoic acid-diethyl azodicarboxylate-triphenylphosphine system and subsequent basic hydrolysis. Azido, phthalimido, and even more complex nucleophile groups could similarly also substitute the allylic hydroxyl groups of 5a and 5b by using the same system, with a few different results between 5a and 5b .

4′-Amino-1,6-anhydro-2,3,2′,3′-tetra- O -benzyl-4′,6′-dideoxy-β-maltose, required as a synthon for the preparation of an α- d -glucosidase inhibitor constituted of a basic pseudotrisaccharide, was prepared from 1,6-anhydromaltose ( 2 ). Two pathways were examined for introducing the amino function into 2 during that synthesis.

"Dihydroacarbose" (2), an alpha-D-glucosidase inhibitor having a pseudo-tetrasaccharide structure, was synthesized by reductive coupling of 4(3)-amino-1(1),6(1)-anhydro-2(1),3(1),2(2),3(2),6(2),2(3),3(3)-hepta-O- benzyl-4(3),6(3)-dideoxy-beta-maltotriose and 2D-(2,4/3,5)-2,3,4-tris(benzyloxy)-5-(trityloxymethyl)cyclohexa non e with sodium-cyanoborohydride. The former intermediate was prepared from a partially benzylated 1(1),6(1)-anhydro-beta-maltotriose, and the latter was prepared from a chiral, penta-substituted cyclohexene derived from D-glucose. The synthetic 2 was found to be a strong, non-competitive inhibitor (Ki = 1.13 x 10(-6) M) against small-intestinal sucrase of rat.