András Lipták

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 of four structural elements of xylose-containing carbohydrate chains from N-glycoproteins

The synthesis of the oligosaccharides beta-D-Xylp-(1----2)-beta-D-Manp-OMe (12), beta-D-Xylp-(1----2)-[alpha-D-Manp-(1----6)]-beta-D-Manp+ ++-OMe (17), beta-D-Xylp-(1----2)-[alpha-D-Manp-(1----3)]-beta-D-Manp+ ++-OMe (21), and beta-D-Xylp-(1----2)-[alpha-D-Manp-(1----3)] [alpha-D-Manp-(1----6)]-beta-D-Manp-OMe (25) is described. Methyl 3-O-benzyl-4,6-O-isopropylidene-beta-D-mannopyranoside (6) was prepared from the corresponding glucoepimer (4) by oxidation, followed by stereoselective reduction. Condensation of 6 with 2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl bromide in the presence of mercuric cyanide gave a 1:9 mixture of methyl 3-O-benzyl-4,6-O-isopropylidene-2-O-(2,3,4- tri-O-acetyl-alpha- (7a) and -beta-D-xylopyranosyl)-beta-D-mannopyranoside (7), and then 7 was converted into the acetylated disaccharide-glycoside 11. Regioselective mannosylation, with 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl bromide, at position 6 of deisopropylidenated 7 (8), using mercuric bromide as a promoter, afforded the trisaccharide-glycoside derivative 13, which was transformed into the acetylated trisaccharide-glycoside 16. The disaccharide derivative 10, obtained from 8, and the trisaccharide derivative 15, obtained from 13, were glycosylated at position 3 with O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)trichloroacetimidate (19), using trimethylsilyl triflate as a promoter, giving rise to acetylated tri- (20) and tetra-saccharide (24) derivatives, respectively. O-Deacetylation of 11, 16, 20, and 24 gave 12, 17, 21, and 25, respectively.

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 the monosaccharide units of the O-specific polysaccharide of Shigella sonnei☆

Abstract The monosaccharide components of the O-specific polysaccharide 1 of the lipopolysaccharide of the enteropathogenic bacterium Shigella sonnei were synthesized as their methyl glycosides 2 and 3 in their natural anomeric form. The key intermediate to the diaminotrideoxygalactose derivative 2 was ethyl 3-O-acetyl-2-deoxy-2-phthalimido-1-thio-β- d -glucopyranoside ( 9 ) that was converted to its ditosylate 10 . Regioselective deoxygenation at C-6 followed by nucleophilic displacement of the secondary tosyloxy group by azide afforded the 4-azido thioglycoside 13 . Methyl trifluoromethanesulfonate-assisted methanolysis of 13 gave the O-glycoside 14 . Replacement of the phthalimido by an acetamido group followed by catalytic reduction of the azido group led to the diamino-trideoxygalactose derivative 2 . The precursor to the l -altruronic acid derivative 3 was methyl α- l -glucopyranoside ( 19 ) that was routinely converted to the benzylidene-protected 2,3-anhydro-allopyranoside 22 . Regioselective opening of the epoxide ring by NaN 3 afforded the 2-azido derivative 23 that was benzylated at HO-3. Hydrolytic removal of the benzylidene group followed by TEMPO oxidation of C-6 and subsequent esterification with MeI gave the key l -azido-altruronic acid intermediate 29 that was transformed to the acetamidoaltruronic acid derivative 3 . High resolution NMR data of the altruronic acid derivatives indicate that the conformation of their pyranose ring is crucially dependent on the substitution pattern: the 2-azido altruronic acid derivatives prefer the 4 C 1 conformation whereas the 2-acetamido congeners exist preferentially in the 1 C 4 conformation.

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 a selectively protected trisaccharide building block that is part of xylose-containing carbohydrate chains from N-glycoproteins

The synthesis is reported of ethyl 4-O-[3-O-allyl-4,6-O-isopropylidene-2-O-(2,3,4-tri-O-acetyl-beta-D- xylopyranosyl)-beta-D-mannopyranosyl]-3,6-di-O-benzyl-2-deoxy-2-phthalim ido-1 - thio-beta-D-glucopyranoside (16), a key intermediate in the synthesis of xylose-containing carbohydrate chains from N-glycoproteins. Condensation of ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-1-thio-beta-D- glucopyranoside (5) with 2,4,6-tri-O-acetyl-3-O-allyl-alpha-D-glucopyranosyl bromide, using silver triflate as a promoter, gave the beta-linked disaccharide derivative 8 (84%). O-Deacetylation of 8 and then isopropylidenation afforded 10, which was converted via oxidation-reduction into ethyl 4-O-(3-O-allyl-4,6-O-isopropylidene-beta-D-mannopyranosyl)-3,6-di-O-benz yl-2- deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (12). Silver triflate-promoted condensation of 12 with 2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl bromide gave 16 (71%). The Xylp unit in 16 and in de-isopropylidenated 16 (17) existed in the 1C4(D) conformation, but that in O-deacetylated 17 (18) existed in the 4C1(D) conformation.

Amphiphilic and mesogenic carbohydrates - II. sysnthesis and Characterisation of mono-o-(n-alkyl)-d-glucose derivates

Abstract The synthesis of various amphiphilic o-(n-alkyl)-D-glucopyranoses, having the long alkyl chain (C8H17 - C16H33) in 2-, 3,- 4-, or 6- position are described. The investigations of the thermal behavior of 6-0-( 13a-e ), 4-0( 14a-e ), 3-0( 15a-e ) and 2-0- (n-alkyl)-D-glucopyranoses ( 16a-e ) and the corresponding methyl-α-D-glucosides 4a-e , 8a-e and 12a-e , respectively, are summarized in this paper.

Action pattern and subsite mapping of Bacillus licheniformis α-amylase (BLA) with modified maltooligosaccharide substrates

This study represents the first characterisation of the substrate‐binding site of Bacillus licheniformis α‐amylase (BLA). It describes the first subsite map, namely, number of subsites, apparent subsite energies and the dual product specificity of BLA. The product pattern and cleavage frequencies were determined by high‐performance liquid chromatography, utilising a homologous series of chromophore‐substituted maltooligosaccharides of degree of polymerisation 4–10 as model substrates. The binding region of BLA is composed of five glycone, three aglycone‐binding sites and a ‘barrier’ subsite. Comparison of the binding energies of subsites, which were calculated with a computer program, shows that BLA has similarity to the closely related Bacillus amyloliquefaciens α‐amylase.

Synthesis of p-trifluoroacetamidophenyl 6-deoxy-2-O-3-O- [2-O-methyl-3-O-(2-O-methyl-α-d-rhamnopyranosyl)- α-l-fucopyranosyl]-α-l-rhamnopyranosyl-α-l- talopyranoside: a spacer armed tetrasaccharide glycopeptidolipid antigen of Mycobacterium avium serovar 20

Abstract The synthesis of the title tetrasaccharide glycoside 38 is reported. p -Nitrophenyl endo -3,4- O -benzylidene-6-deoxy-α- l -talopyranoside ( 4 , 3- O -acetyl-2,4-di- O -benzyl-α- l -rhamnopyranosyl trichloroacetimidate ( 7 ), methyl 3- O -acetyl-4- O -benzyl-2- O -methyl-1-thio-β- l -fucopyranoside ( 15 ) 3- O -acetyl-4- O -benzyl-2- O -methyl-α- l -fucopyranosyl bromide ( 16 ), and ethyl 3- O -acetyl-4- O -benzyl-2- O -methyl-1-thio-α- d -rhamnopyranoside ( 33 ) were prepared as intermediates. Compound 4 was glycosylated with imidate 7 as well as with methyl 3- O -acetyl-2,4-di- O -benzyl-1-thio-α- l -rhamnopyranoside ( 9 ), affording the same disaccharide derivative 8 . Deacetylation of 8 gave crystalline 17 . Condensation of 17 with both fucosyl donors 15 and 16 yielded the same trisaccharide derivative 18 stereoselectively. Compound 18 was also prepared by the coupling of 4 with disaccharide glycosyl donor 20 . After deacetylation of 18 (→ 34 ), methyl triflate-promoted glycosylation with compound 33 resulted in tetrasaccharide 35 . Conversion of the p -nitrophenyl group of 35 into the p -trifluoroacetamidophenyl group (→ 36 ) and removal of the protecting groups gave the title tetrasaccharide glycoside 38 .