Synthetic α,β(1→4)-Glucan Oligosaccharides as Models for Heparan Sulfate

Abstract

α,β-(1→4)-Glucans were devised as models for heparan sulfate with the simplifying assumptions that carboxyl-reduction and sulfation of heparan sulfate does not decrease the SMC antiproliferative activity and that N-sulfates in glucosamines can be replaced by O-sulfates. The target oligo-saccharides were synthesized using maltosyl building blocks. Glycosylation of methyl 2,3,6,2′,3′,6′-hexa-O-benzyl-β-maltoside (1) with hepta-O-acetyl-α-maltosyl bromide (2) furnished tetrasaccharide 3 which was deprotected to α-D-Glc-(1→4)-β-D-Glc-(1→4)-α-D-Glc-(1→4)-β-D-Glc-(1→OCH₃) (5) or, alternatively, converted to the tetrasaccharide glycosyl acceptor (8) with one free hydroxyl function (4?′-OH). Further glycosylation with glucosyl or maltosyl bromide followed by deblocking gave the pentasaccharide [β-D-Glc-(1→4)-α-D-Glc-(1→4)]₂-β-D-Glc-(1→OCH₃) (11) and hexasaccharide [α-D-Glc-(1→4)-β-D-Glc-(1→4)₂-α-D-Glc-(1→4)-β-D-Glc-(1→OCH₃) (14). The protected tetrasaccharide 3 and hexasaccharide 12 were fully characterized by ¹H and ¹³C NMR spectroscopy. Assignments were possible using 1D TOCSY, T-ROESY, ¹H,¹H 2D COSY supplemented by ¹H-detected one-bond and multiple-bond ¹H,¹³C 2D COSY experiments.     

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.     

Synthesis of Oligosaccharides Designed to form Micelles,Corresponding to Structures Found in Ovarian Cyst Fluid

ABSTRACT

The syntheses of α-D-GlcpNAc-(1→4)-β-D-Galp-(1→4)-β-D-GlcNAc-(1→O)-(CH₂)₁₅CH₃ (1) and fragments thereof, corresponding to structures found in human ovarian cyst fluid, are described. Silver triflate promoted coupling of 3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-glucopyranosyl bromide (12) and galactose acceptor (11) gave a disaccharide donor (13), which was readily transformed into the corresponding bromo-derivative 18. For the synthesis of disaccharide β-D-Galp-(1→4)-D-GlcNAc, several differently protected glucosamine acceptors were prepared. It was found that cetyl alcohol needed to be introduced after the formation of the β-galactoside bond. Glycosylation of pent-4-enyl 3,6-di-O-benzyl-2-deoxy-2-tetrachlorophthalimido-β-D-glucopyranoside (30) with (3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-benzoyl-α-D-galactopyranosyl bromide (18) by use of silver triflate as promoter gave the desired trisaccharide 31. Finally 31 was transformed via coupling to the long alkyl chain aglycon and deprotection into the title compound 1.     

A NEW APPROACH TO A DISACCHARIDIC HAPTEN CONTAINING A GALACTOFURANOSYL ENTITY1-2

A short synthetic entry into the disaccharidic hapten β-D-Galf-(1→3)-α-D-Manp-O(CH₂)₈CO₂Me containing a galactofuranosyl entity at the non-reducing part is described. The synthetic scheme was designed in such a way that each required building block could be obtained by minimizing the number of chemical and purification steps. Indeed, compound 8 was obtained according to a four step–one pot preparation.     

Über triterpene—XXIX : Zur struktur des avenacins

From the roots of oat (Avena sativa) a second antibiotic active glycoside, avenacine B, was isolated in addition to the main glycoside avenacine A. In the aglycone of A the double bond could not be established contrary to the statement in the literature but an aldehyde group in addition to the keto group was identified and therefore the proposed structure has to be revised. In the aglycone of B the —CH₂OH-group of A has been substituted by CH₃. The structures of the sugar chains in both glycosides have been determined, in avenacine A as [β-d-gluco-pyranosyl(1 → 4)-[β-d-glucopyranosyl (1 → 2)]-α-l-arabinosyl (1)- and in B as [β-d-glucopyranosyl (1 → 4)]-β-d-glucopyranosyl (1)-.     

Stereoselective Synthesis of a Tetrameric Fragment of Streptococcus Pneumoniae Type 1 Containing an α-Linked 2-Acetamido-4-amino-2,4,6-trideoxy-D-galactopyranose (SUGp) Unit

Abstract

Block condensation of fully protected donor ethyl 1,2,3,4-tetra-O-benzyl-D-Rib-(5→P→6)-2,3,4-tri-O-benzoyl-l-thio-β-D-Glcp (2), having a (5→6)-phosphotriester union between the ribitol and the glucopyranosyl moieties, with the free 3′-OH group in the acceptor methyl 2-acetamido-4-O-(2-acetamido-4-(benzyloxycarbonyl)amino-2,4,6-trideoxy-α-D-Galp)-3,6-di-O-benzyl-2-deoxy-α-D-Galp (3), under the agency of N-iodosuccinimide and triflic acid, gave the fully protected tetrameric fragment 22. Elimination of the 2-cyanoethyl group from the phosphotriester and subsequent debenzoylation, followed by hydrogenolysis of the benzyl and benzyloxycarbonyl groups provided the target tetramer methyl D-Rib-(5→P→6)-D-Glcp-β(1→3)-Sugp-α(1→4)-α-D-GalpNAc (1).     

Synthesis of new α,α,β,β-tetrafluoroesters

Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF₂CF₂CO₂Et, 1 in the presence of copper powder to give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and allyl acetate proceeded smoothly under thermal and radical conditions to give the corresponding adducts, which underwent elimination reaction to give β-vinyl and β-allyl α,α,β,β-tetrafluoroesters, CH₂CHCF₂CF₂CO₂Et, 4 and CH₂CHCH₂CF₂CF₂CO₂Et, 5, respectively. 1 also readily reacted with 1,5-hexadiene and 1-hexene with copper or palladium complex, followed by reduction to remove iodine to produce ω-alkenyl-α,α,β,β-tetrafluoroester CH₂CH(CH₂)₄CF₂CF₂CO₂Et 6 and α,α,β,β-tetrafluoroester C₄H₉CH₂CHICF₂CF₂CO₂Et.     

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 AND CATIONIC RING-OPENING POLYMERIZATION OF 1, 4-ANHYDRO-2, 3-DI-O-(P-AZIDOBENZYL)-α-D-RIBOPYRANOSE

New highly stereoregular 2, 3 -di- O-(p-azidobenzyl )-(1 →5 ) - α-D -ribofuranan was synthesized byselective ring-opening polymerization of 1, 4-anhydro-2, 3 - di-O -(p-azidobenzyl )-α-D -ribopyranose(ADABR) using phosphorus pentafluoride or tin tetrachloride as catalyst at low temperature indichloromethane. The monomer was obtained by the reaction of p - bromomethyl -phenyleneazide with 1, 4 -anhydro-α-D-ribose in DMF. The structure of poly(ADANR) was identified by specific rotation and ~(13)C-NMR spectroscopy. Acid chloride-AgCl_4 complex catalyst such as CH_2=C(CH_3)C~+OClO_4~- used in thepolymerization resulted in polymers with mixed structures, i.e. (1→5)-α-D-ribofuranosidic and (1→4)-β-D-ribopyranosidic units. However, with C_6H_5C~+OClO_4~- as catalyst, pure (1→5)-α-D-ribofuranan was obtained.The effects of catalyst, polymerization temperature and time on polymer stereoregularity were examined, andthe mechanism of the ring-opening polymerization was discussed.     

Synthetic oligosaccharides as tools to demonstrate cross-reactivity between polysaccharide antigens

Escherichia coli O148 is a nonencapsulated enterotoxigenic (ETEC) Gram negative bacterium that can cause diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome in humans. The surface-exposed O-specific polysaccharide (O-SP) of the lipopolysaccharide of this bacterium is considered both a virulence factor and a protective antigen. It is built up of the linear tetrasaccharide repeating unit [3)-α-L-Rhap-(1→2)-α-D-Glcp-(1→3)-α-D-GlcNAcp-(1→3)-α-L-Rhap-(1→] differing from that of the O-SP of Shigella dysenteriae type 1 (SD) only in that the latter contains a D-Galp residue in place of the glucose moiety of the former. The close similarity of the O-SPs of these bacteria indicated a possible cross-reactivity. To answer this question we synthesized several oligosaccharide fragments of E. coli O148 O-SP, up to a dodecasaccharide, as well as their bovine serum albumin or recombinant diphtheria toxin conjugates. Immunization of mice with these conjugates induced anti-O-SP-specific serum IgG antibody responses. The antisera reacted equally well with the LPSs of both bacteria, indicating cross-reactivity between the SD and E. coli O148 O-SPs that was further supported by Western-blot and dot-blot analyses, as well as by inhibition of binding between the antisera and the O-SPs of both bacteria.     

Are the anions MeO(CO) (n = 1 and 2) methoxide anion donors in the gas phase? A theoretical investigation

• 1. The anions CH₃O‐^–CO and CH₃OCO‐^–CO are both methoxide anion donors. The processes CH₃O‐^–CO → CH₃O^– + CO and CH₃OCO—CO → CH₃O^– + 2CO have ΔG values of +8 and ?68 kJ mol^?1, respectively, at the CCSD(T)/6‐311++G(2d, 2p)//B3LYP/6‐311++G(2d,2p) level of theory.
• 2. The reactions CH₃OCOCO → CH₃OCO + CO (ΔG = ?22 kJ mol^?1) and CH₃COCH(O^–)CO₂CH₃ → CH₃COCH(O^–)OCH₃ + CO (ΔG = +19 kJ mol^?1) proceed directly from the precursor anions via the transition states (CH₃OCO…CO₂)^– and (CH₃COCHO…CH₃OCO)^–, respectively.
• 3. Anion CH₃COCH(O^–)CO₂CH₃ undergoes methoxide anion transfer and loss of two molecules of CO in the reaction sequence CH₃COCH(O^–)CO₂CH₃ → CH₃CH(O^–)COCO₂CH₃ → [CH₃CHO (CH₃OCO‐^–CO)] → CH₃CH(O^–)OCH₃ + 2CO (ΔG = +9 kJ mol^?1). The hydride ion transfer in the first step is a key feature of the reaction sequence.

Copyright © 2010 John Wiley & Sons, Ltd.     

Preparation and Characterization of the Enzymatic Degradation Products of the Exopolysaccharide From Klebsiella K13

Oligosaccharides were prepared from the exopolysaccharide of Klebsiella K13 by enzymatic degradation and characterized. A phage-borne depolymerase enzyme was used to degrade the exopolysaccharide of Klebsiella K13. Bio-Gel P4 and P6 were used to purify the oligosaccharide products. The purified oligosaccharides were characterized by HPLC, mass spectroscopy, infrared spectroscopy, and NMR spectroscopy. The monosaccharide constituents of these enzymatic degradation products include D-glucose, D-galactose, D-mannose, and D-glucuronic acid. It was concluded that a pentasaccharide repeating unit with the following structure, as well as its dimer and trimer, was released from the exopolysaccharide: 3,4-O-(1-carboxyethylidene)-β-D-Galp-(1→4)-α-D-GlcpA-(1→3)-β-D-Manp-(1→4)-α-D-Glcp-(1→3)-D-Glcp     

Probing the Helical Secondary Structure of Short-Chain β-Peptides

Structural prerequisites for the stability of the 3₁ helix of β-peptides can be defined from inspection of models (Figs. 1 and 2): lateral non-H-substituents in 2- and 3-position on the 3-amino-acid residues of the helix are allowed, axial ones are forbidden. To be able to test this prediction, we synthesized a series of heptapeptide derivatives Boc-(β-HVal-β-HAla-β-HLeu-Xaa-β-HVal-β-HAla-β-HLeu)-OMe 13–22 (Xaa = α- or β-amino-acid residue) and a β-depsipeptide 25 with a central (S)-3-hydroxybutanoic-acid residue (Xaa = –OCH(Me)CH₂C(O)–) (Schemes 1 3). Detailed NMR analysis (DQF-COSY, HSQC, HMBC, ROESY, and TOCSY experiments) in methanol solution of the β-hexapeptide H(-β-HVal-β-HAla-β-HLeu)₂-OH ( 1 ) and of the β-heptapeptide H-β-HVal-β-HAla-β-HLeu-(S,S)-β-HAla(αMe)-β-HVal-β-HAla- β-HLeu-OH ( 22 ), with a central (2S,3S)-3-amino-2-methylbutanoic-acid residue, confirm the helical structure of such β-peptides (previously discovered in pyridine solution) (Fig.3 and Tables 1–5). The CD spectra of helical β-peptides, the residues of which were prepared by (retentive) Arndt-Eistert homologation of the (S)- or L -α-amino acids, show a trough at 215 nm. Thus, this characteristic pattern of the CD spectra was taken as an indicator for the presence of a helix in methanol solutions of compounds 13–22 and 25 (including partially and fully deprotected forms) (Figs.4–6). The results fully confirm predicted structural effects: incorporation of a single ‘wrong’ residue ((R)-β-HAla, β-HAib, (R,S)-β-HAla(α Me), or N-Me-β-HAla) in the central position of the β-heptapeptide derivatives A (see 17, 18, 20 , or 21 , resp.) causes the CD minimum to disappear. Also, the β-heptadepsipetide 25 (missing H-bond) and the β-heptapeptide analogs with a single α-amino-acid moiety in the middle ( 13 and 14 ) are not helical, according to this analysis. An interesting case is the heptapeptide 15 with the central achiral, unsubstituted 3-aminopropanoic-acid moiety: helical conformation appears to depend upon the presence or absence of terminal protection and upon the solvent (MeOH vs. MeOH/H₂O).     

Synthesis of tetra- and hexasaccharide fragments corresponding to the O-antigenic polysaccharide of Klebsiella pneumoniae

The preparation of linear tetra- (1) and hexasaccharides (2), containing the repeating unit [→3)-β-Galf-(1→3)-α-Galp-(1→] present in the O-polysaccharide of the lipopolysaccharide of Klebsiella pneumoniae is described. The key step in their synthesis is the α-selective galactopyranosylation of 3-OH di- and tetrasaccharide acceptors (20 and 22) with a disaccharide trichloroacetimidate donor 19 in the presence of trimethylsilyl triflate in a diethyl ether–CH₂Cl₂ mixture as solvent.     

Studies towards a Conjugate Vaccine for Anthrax: Synthesis of the Tetrasaccharide Side Chain of the Bacillus anthracis Exosporium

The first synthesis of β‐L ‐glycoside 17 of the tetrasaccharide β‐Ant‐(1 → 3)‐α‐L ‐Rhap‐(1 → 3)‐α‐L ‐Rhap‐(1 → 2)‐L ‐Rhap is described (Schemes 1–3). Its spacer can be functionalized to make it amenable to conjugation to proteins by different conjugation methods. The synthesis was performed in a stepwise manner starting from the aglycon‐bearing terminal saccharide with thioglycosides as glycosyl donors. To attach the upstream terminal anthrose residue, the assembled linker‐equipped trisaccharide was glycosylated with ethyl 4‐azido‐3‐O‐benzyl‐2‐O‐(bromoacetyl)‐4,6‐dideoxy‐1‐thio‐β‐D ‐glucopyranoside ( 11 ). Further functionalization of the tetrasaccharide thus obtained, followed by deprotection gave the target substance 17 . Synthesis of substructures of 17 equipped with the same spacer, namely β‐L ‐Rhap‐1‐O‐(CH₂)₅COOMe ( 21 ), α‐L ‐Rhap‐(1 → 2)‐β‐L ‐Rhap‐1‐O‐(CH₂)₅COOMe ( 22 ), and α‐L ‐Rhap‐(1 → 3)‐α‐L ‐Rhap‐(1 → 2)‐β‐L ‐Rhap‐1‐O‐(CH₂)₅COOMe ( 23 ), is also described (Scheme 4).     

Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT

The stereocontrolled synthesis of methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (EC, 1), methyl α-L-rhamnopyranosyl-(1→3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (B(E)C, 3) and methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyl-α-L-rhamnopyranoside (11) and 8 afforded the fully protected αE-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding βE-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding βE-disaccharide, namely, methyl β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (βEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the αE and βE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required αE-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2,3-di-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.     

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.     

Insertion Reactions of [ReH(CO)5–n(PMe3)n] Complexes (n = 2–4) with aldehydes,CO2, and activated acetylenes

The complexes of the type [ReH(CO)_5–n(PMe₃)_n] (n = 4, 3) were reacted with aldehydes, CO₂, and RC?CCOOMe (R = H, Me) to establish a phosphine-substitutional effect on the reactivity of the Re–H bond. In the series 1–3 , benzaldehyde showed conversion with only 3 to afford a (benzyloxy)carbonyltetrakis(trimethylphosphine)rhenium complex 4 . Pyridine-2-carbaldehyde allowed reaction with all hydrides 1–3 . With 1 and 2 , the same dicarbonyl[(pyridin-2-yl)methoxy-O, N]bis(trimethylphosphine)rhenium 5b was formed with the intermediacy of a [(pyridin-2-yl)methoxy-O]-ligated species and extrusion of CO or PMe₃, respectively. The analogous conversion of 3 afforded the carbonyl[(pyridin-2-yl)methoxy-O,N]tris(trimethylphosphine)rhenium ( 1 ) 7b . While 1 did not react with CO₂, 2 and 3 yielded under relatively mild conditions the formato-ligated [Re(HCO₂)(CO)(L)(PMe₃)₃] species ( 8 (L = CO) and 9 (L = PMe₃)). Methyl propiolate and methyl butynoate were transformed, in the presence of 1 , to [Re{C(CO₂Me)?CHR}(CO)₃(PMe₃)₂] systems ( 10a (R = H), and 10b (R = Me)), with prevailing α-metallation and trans-insertion stereochemistry. Similarly, HC≡CCO₂Me afforded with 2 and 3 , the α-metallation products [Re{C(CO₂Me)?CH₂}(CO)(L)(PMe₃)₃] 11 (L = CO) and 12 (L = PMe₃). The methyl butyonate insertion into 2 resulted in formation of a mixture of the (Z)- and (E)-isomers of [Re{C(CO₂Me)?CHMe} (CO)₂(PMe₃)₃] ( 13a , b ). In the case of the conversion of 3 with MeC?CCO₂Me, a Re–H cis-addition product [Re{(E)-C(CO₂Me)?CHMe}(CO)(PMe₃)₄] ( 14 ) was selectively obtained. Complex 11 was characterized by an X-ray crystal-structure analysis.     

Triterpene glycosides of Hedera taurica

From the leaves of Crimean ivy we have isolated the previously known glycosides 3-O-α-L-Ara_p-28-O-[O-α-L-Rha_p-(1→4)-O-β-D-Glc_p-(1→6)-β-D-Glc_p]hederagenin, 3-O-[O-α-L-Rha_p-(1→2)-α-L-Ara_p]-28-O-[O-α-L-Rha_p-(1→4)-O-β-D-Glc_p-(1→6)-β-D-Glc_p]oleanic acid and -hederagenin, and 3-O-[O-α-L-Rha_p-(1→2)-α-L-Ara_p]-28-O-[O-β-D-Glc_p-(1→6)-β-D-Glc_p]hederagenin and a new one: tauroside H₁ — 3-O-[O-α-L-Rha_p-(1→2)-O-α-L-Ara_p]-28-O-[O-α-L-Rha_p-(1→4)-O-β-D-Glc_p-(1→6)-β-D-Glc_p]echinocystic acid.     

SYNTHESIS OF SIALYL-α-(2→3)-NEOLACTOTETRAOSE DERIVATIVES MODIFIED AT C-2 OF THE N-ACETYLGLUCOSAMINE RESIDUE: PROBES FOR INVESTIGATION OF ACCEPTOR SPECIFICITY OF HUMAN α-1,3-FUCOSYLTRANSFERASES,FUC-TVII,AND FUC-TVI *

A variety of sialyl-α-(2→3)-neolactotetraose (IV³NeuAcnLcOse₄ or IV³NeuGcnLcOse₄) derivatives (23, 31–37, 58–60) modified at C-2 of the GlcNAc residue have been synthesized. The phthalimido group at C-2 of GlcNAc in 2-(trimethylsilyl)ethyl (3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→3)-(2,4,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (5) was systematically converted to a series of acylamino groups, to give the per-O-benzylated trisaccharide acceptors (6–11). On the other hand, modification of the hydroxyl group at C-2 of the terminal Glc residue in 2-(trimethylsilyl)ethyl (4,6-O-benzylidene-β-d-glucopyranosyl)-(1→3)-(2,4,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-d-glucopyranoside (42) gave three different kinds of trisaccharide acceptors containing D-glucose (49), N-acetyl-d-mannosamine (50), and D-mannose (51) instead of the GlcNAc residue. Totally ten trisaccharide acceptors (5–11 and 49–51) were each coupled with sialyl-α-(2→3)-galactose donor 12 to afford the corresponding pentasaccharides (14–21 and 52–54) in good yields, respectively, which were then transformed into the target compounds. Acceptor specificity of the synthetic sialyl-α-(2→3)-neolactotetraose probes for the human α-(1→3)-fucosyltransferases, Fuc-TVII and Fuc-TVI, was examined.