Pál Nánási

Stereoselective ring-cleavage of 3-O-benzyl- and 2,3-di-O-benzyl-4,6-O-benzylidenehexopyranoside derivatives with the LiAlH4AlCl3, reagent

Abstract Hydrogenolysis of 3- O -benzyl- and 2,3-di- O -benzyl-4,6- O -benzylidene- d -gluco- and - d -manno-pyranoside derivatives with LiAlH 4 AlCl 3 , gives the corresponding 4- O -benzyl compounds. The direction of cleavage of the benzylidene ring is determined by the presence of a benzyl group at position 3, but it is not dependent on the anomeric configuration, substitution at O-2, or the character of the aglycon moiety. For 2,3-di- O -benzyl-4,6- O -benzylidene- d -galactopyranoside derivatives, the ratio of the resulting 4- and 6- O -benzyl compounds is ~ 9:1 and is independent of the anomeric configuration. Substitution at O-3 with a group less-bulky than benzyl favours the formation of 6- O -benzyl compounds.

Chemo-, stereo- and regioselective hydrogenolysis of carbohydrate benzylidene acetals. Synthesis of benzyl ethers of benzyl α-d-, methyl β-D-mannopyranosides and benzyl α-D-rhamnopyranoside by ring cleavage of benzylidene derivatives with the LiAlH4-AlCl3 reagent

Abstract Treatment of benzyl α-(1) and methyl β- d -mannopyranoside (2) with α,α-dimethoxytoluene gave the exo and endo isomers (3,5 and 4,6) of the dibenzylidene derivatives of 1 and 2. Hydrogenolysis of the exo isomers (3 and 5) with a molar equivalent of AlH2Cl gave the 3-0-benzyl-4,6-0-benzylidene derivatives (7 and 21), whereas the endo isomers (4 and 6) gave the 2-0-benzyl-4,6-0-benzylidene compounds (8 and 22). The 2-0-allyl ether 9 of 7, the 3-0-allyl derivative (10) of 8 and compounds 21 and 22 were treated with an additional molar equivalent of AlH2Cl at reflux and the products were the 4-0-benzyl-6-hydroxyl derivatives (11, 12, 23 and 24), whereas in the case of 22 the 6-0-benzyl-4-hydroxyl isomer (25) was also isolated. By deallylation of 11 and 12, 3,4-(13) and 2,4-di-0-benzyl (14) ethers of 1 were prepared. Tosylation of 11 and 12, and subsequent reduction of the products (15 and 16) made possible the preparation of the partially protected benzyl α- d -rhamnopyranoside derivatives (17–20). The structures of the compounds synthesized were characterized by 1H and 13C NMR spectroscopic investigation and by chemical methods.

Synthesis and 13C-NMR spectroscopic investigations of rhamnobioses

Abstract A convenient method has been developed for the synthesis of all mono- and di-O-benzyl ethers of methyl α-L-rhamnopyranoside applying a new stereoselective method for the hydrogenolytic ring-cleavage of benzylidene acetals. Using the prepared dibenzyl ethers as aglycones, the (1→2)-, (1→3)- and (l→4)-linked rhamnosyl-rhamnose derivatives ( 13 – 15 ) were synthesised. Hydrogenolysis of the latter compounds and subsequent acetylation gave the pentaacetates ( 16 – 18 ) of methyl dirhamnosides, which on saponification furnished the free methyl dirhamnosides ( 19 – 21 ). Acetolysis of 16 – 18 gave the corresponding dirhamnose-hexaacetates which were transformed into the three disaccharides by saponification. The structure of each product was investigated by 13 C-NMR spectroscopy, and for the purpose of 13 C-NMR studies the mono-O-methyl ethers of methyl α-L-rhamnopyranoside, the diacetates and di-O-benzyl ethers of the latter compounds, and, also the diacetates of methyl α-L-rhamnopyranoside were synthesised. It has been established that, for 13 C-NMR investigations of oligosaccharides, the benzyl ethers of monosaccharides are more suitable model compounds than the currently used monosaccharide methyl ethers.

Synthesis of mono- and di-benzyl ethers of benzyl α-l-rhamnopyranoside

Abstract Benzylidenation of benzyl α- l -rhamnopyranoside ( 1 ) gave the exo - ( 2 ) and endo -2,3- O -benzylidene diastereomers ( 3 ), hydrogenolysis of which afforded the 3-benzyl and 2-benzyl ethers of 1 , respectively. Hydrogenolysis of the 4- O -benzyl derivatives ( 14 and 15 ) of 2 and 3 yielded the 3,4-di-benzyl and 2,4-dibenzyl ethers of 1, whereas hydrolysis of 14 and 15 gave the 4 -benzyl ether of 1 . The 2,3-dibenzyl ether of 1 was synthesised via the 4- O -allyl derivative of 1.

Synthesis of 6-O-α-d-glucopyranosylcyclomaltoheptaose

Abstract (2,3-Di- O -acetyl)hexakis(2,3,6-tri- O -acetyl)cyclomaltoheptaose was prepared by reaction of cyclomaltoheptaose with tert -butyldimethylsilyl chloride in pyridine followed by acetylation and desilylation. Glycosylation with 2,3,4,6-tetra- O -benzyl-1- O -trichloroacetimidoyl-α- d -glucopyranose, using trifluoromethanesulfonic acid as catalyst, and removal of the protecting groups from the product then afforded the title compound.

Hydrogenolysis of benzylidene acetals: synthesis of benzyl 2,3,6,2′,3′,4′-hexa-O-benzyl-β-cellobioside, -maltoside, and -lactoside, benzyl 2,3,4,2′,3′,4′-hexa-O-benzyl-β-allolactiside, and benzyl 2,3,6,2′,3′,6′-hexa-O-benzyl-β-lactoside

Abstract Hydrogenolysis of benzyl penta- O -benzyl-4′,6′- O -benzylidene-β-cellobioside (4) , -maltoside (5) , and -allolactoside (16) with LiAlH 4 -AlCl 3 gave only the corresponding derivatives having HO-6′ free, in yields of 55, 78, and 90%, respectively. The main product of the hydrogenolysis of benzyl penta- O -benzyl-4′,6′- O -benzylidene-β-lactoside (6) also had HO-6′ free, but the isomer having HO-4′ free was also isolated. The role of the C-1 substituent in the galactose moiety in the direction of benzylidene ring-cleavage is discussed.

The regioselectivity of the reductive ring-cleavage of the acetal ring of 4,6-O-benzylidenehexopyranosides

Abstract The hydrogenolytic ring-cleavage of benzyl 4,6- O -benzylidene-β- d -glucopyranoside derivatives with LiAlH 4 -AlCl 3 was investigated in relation to the bulk of the C-3 substituents (H, OMe, OEt, OPr, OBzl). In ether-dichloromethane (2:1), 4-benzyl ethers were the major products, and the ratio of the 4- and 6-benzyl ethers was strongly dependent on the steric requirement of the C-3 substituent. Hydrogenolytic ring-cleavage with various reducing agents (AlH 2 Cl, AlH 2 Br, AlH 2 I, Bu 2 1 AlH, and borane) was also studied and the best selectivity was found with AlH 2 Br. The donor ability of the solvent has significant effects on the product ratios and the reaction rates in some reductions.

Synthesis, and carbon-13 n.m.r. study, of O-α-l-rhamnopyranosyl-(1→3)-O-α-l-rhamnopyranosyl-(1→2)-l-rhamnopyranose and O-α-l-rhamnopyranosyl-(1→3)-O-α-l-rhamnopyranosyl (1→3)-l-rhamnopyranose, constituents of bacterial, cell-wall polysaccharides

Abstract O -α- l -Rhamnopyranosyl-(1→3)- l -rhamnopyranose ( 19 ) and O -α- l -rhamnopyranosyl-(1→2)- l -rhamnopyranose were obtained by reaction of benzyl 2,4- ( 7 ) and 3,4-di- O -benzyl-α- l -rhamnopyranoside ( 8 ) with 2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl bromide, followed by deprotection. The per- O -acetyl α-bromide ( 18 ) of 19 yielded, by reaction with 8 and 7 , the protected derivatives of the title trisaccharides ( 25 and 23 , respectively), from which 25 and 23 were obtained by Zemplen deacetylation and catalytic hydrogenolysis, With benzyl 2,3,4-tri- O -benzyl-β- d -galactopyranoside, compound 18 gave an ≈3:2 mixture of benzyl 2,3,4-tri- O -benzyl-6- O -[2,4-di- O -acetyl-3- O -(2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl)-α- l -rhamnopyranosyl]-β- d -galactopyranoside and 4- O -acetyl-3- O -(2,3,4-tri- O -acetyl-α- l -rhamnopyranosyl)-β- l -rhamnopyranose 1,2-(1,2,3,4-tetra- O -benzyl-β- d -galactopyranose-6-yl (orthoacetate). The downfield shift at the α-carbon atom induced by α- l -rhamnopyranosylation at HO-2 or -3 of a free α- l -rhamnopyranose is 7.4-8.2 p.p.m., ≈1 p.p.m. higher than when the (reducing-end) rhamnose residue is benzyl-protected (6.6-6.9 p.p.m.). α- l -Rhamnopyranosylation of HO-6 of gb- d -galactopyranose deshields the C-6 atom by 5.7 p.p.m. The 1 2-orthoester ring structure [O 2 ,C(me)OR] gives characteristic resonances at 24.5 ±0.2 p.p.m. for the methyl, and at 124.0 ±0.5 p.p.m. for the quaternary, carbon atom.

Synthesis of 2-O-α-, 3-O-α-, 3-O-β-, and 4-O-α-l-rhamnopyranosyl-d-galactose

Condensation of benzyl 3-O-benzoyl-4,6-O-benzylidene-, benzyl 2-O-benzoyl-4,6-O-benzylidene- (2), and benzyl2,3,6-tri-O-benzyl-⨿-d-galactopyranoside, separately, with tri-O-acetyl-α-l-rhamnopyranosyl bromide gave mainly α-linked disaccharide derivatives. An appreciable proportion of the ⨿-linked disaccharide was also obtained from 2. An anomalous deacylation reaction was found for the (1→3)-linked disaccharide, and the partially benzoylated products were isolated and characterised. The anomeric configuration of each disaccharide was established on the basis of JC-1,H-1 values. The chemical shifts for the galactose moieties of the α- and β-l-rhamnopyranosyl derivatives differed in a systematic way.

Synthesis of 4-O-α-d-galactopyranosyl-l-rhamnose and 4-O-α-d-galactopyranosyl-2-O-β-glucopyranosyl-l-rhamnose using dioxolane-type benzylidene acetals as temporary protecting-groups

Abstract The Halide ion-catalysed reaction of benzyl exo -2,3- O -benzylidene-α- l -rhamnopyranoside with tetra- O -benzyl-α- d -galactopyranosyl bromide and hydrogenolysis of the exo -benzylidene group of the product 2 gave benzyl 3- O -benzyl-4- O -(2,3,4,6-tetra- O -benzyl-α- d -galactopyranosyl)-α- l -rhamnopyranoside ( 6 ). Compound 2 was converted into 4- O -α- d -galactopyranosyl- l -rhamnose. The reaction of 6 with tetra- O -acetyl-α- d -glucopyranosyl bromide and removal of the protecting groups from the product gave 4- O -α- d -galactopyranosyl-2- O -β- d -glucopyranosyl- l -rhamnose.