Synthesis Of Ligands Related To The O-Specific Antigen Of Shigella Dysenteriae Type 1.

Abstract

Stereoselective α-D-galactosylation at the position 3 of 4,6-O-substituted derivatives of methyl 2-acetamido-2-deoxy-α-D-glucopyranoside is described. Glycosyl chlorides derived from 3,4,6-tri-O-acetyl-2-O-benzyl- and 2-O-(4-methoxybenzyl)-D-galactopyranose have been used as glycosyl donors. Methyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (27) and methyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (31) have been prepared.     

C-4 EPIMERIZATION OF α-D-GLUCOPYRANOSIDE: A FACILE SYNTHESIS OF 4-O-ACETYL-α-D-GALACTOPYRANOSYL DERIVATIVES

An unexpected epimerization resulting from the reaction of α-D-glucopyranosyl derivatives with DAST is described. The reaction of 3,4-di-O-acetyl-1,6-di-O-trityl-β-D-fructofuranosyl 2,3,6-tri-O-acetyl-α-D-glucopyranoside (1), methyl 2,3-di-O-acetyl-6-O-trityl-α-D-glucopyranoside (6), 2,3-di-O-acetyl-6-O-trityl-α-D-glucopyranosyl 2,3-di-O-acetyl-6-O-trityl-α-D-glucopyranoside (13), and 2,3-di-O-acetyl-6-O-tert-butyldiphenylsilyl-α-D-glucopyranosyl 2,3,4,6-tetra-O-acetyl-α-D-glucopyranoside (14) with DAST at 0°C did not give the expected C-4 fluorodeoxy galacto derivatives, but instead, the corresponding 4-O-acetyl-3-hydroxy-α-D-galactopyranosides in yields of 52–78%. When the treatment of 6 was carried out at ?25°C for ～5 min the corresponding diastereomeric 4-O-diethylaminosulfinates (9a,b) were isolated as the major products (40%). Evidence suggests that the epimerization reaction most probably resulted from an intramolecular displacement of the intermediate diethylaminosulfur difluoride ester or diethylaminosulfinyl ester by the neighbouring acetoxy groups.     

2-Deoxy-2-C-(2,3-dideoxy-α-d-erythro-hexopyranosyl)-β-d-glucopyranoses: Reinvestigation of Synthesis,Use in Glycosylation,and Conformational Analyses by NMR

Abstract

Conformational investigations using 1D TOCSY and ROESY ¹H NMR experiments on 1,3,4,6-tetra-O-acetyl-2-C-(4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hexopyranosyl)-2-deoxy-β-D-glucopyranose (8) and related disaccharides showed that for steric reasons the C-linked hexopyranosyl ring occurs in the usually unfavoured ¹C₄ conformation and reconfirmed the structure of 1,3,4,6-tetra-O-acetyl-2-C-(4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosyl)-2-deoxy-β-D-glucopyranose (5). Glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3-di-O-benzyl-4,6-(R)-O-benzylidene-α-D-glucopyranoside (13) with acetate 8 using trimethylsilyl triflate as a catalyst afforded the α-D-linked tetrasaccharide 14. A remarkable side product in this reaction was the unsaturated tetrasaccharide 2,3,6-tri-O-benzyl-4-O-[4,6-di-O-acetyl-2,3-dideoxy-2-C-(4,6-di-O-acetyl-2,3-dideoxy-β-D-erythro-hexopyranosyl)-α-D-erythro-hex-2-enopyranosyl]-α-D-glucopyranosyl 2,3-di-O-benzyl-4,6-(R)-O-benzylidene-α-D-glucopyranoside (16) where in the C-linked hexopyranosyl ring an isomerization to the β-anomer had taken place to allow for the favoured ⁴C₁ conformation. The tetrasaccharide 14 was deacetylated and hydrogenolyzed to form the fully deprotected tetrasaccharide 18. The ¹ C ₄ conformation of the C-glycosidic pyranose of this tetrasaccharide was maintained as shown by an in depth NMR analysis of its peracetate 19.     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes. II. the Synthesis of the 4- and 4′″-Monodeoxygenated Analogues

ABSTRACT

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at positions 4 or 4′″ have been synthesized in [2+2] block syntheses. After the preparation of precursors with only one free hydroxyl group the deoxy function was introduced by a Barton-McCombie reaction. Thus, glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside (4) with octa-O-acetyl-β-maltose (3) gave tetrasaccharide 5 with only one free hydroxyl group at the 4-position. The 4′-position of an allyl maltoside was available selectively after removal of a 4′,6′-cyclic acetal and selective benzoylation of the 6′-position. Reduction of this derivative 11 afforded allyl O-(2,3-di-O-acetyl-6-O-benzoyl-4-deoxy-α-D-glucopyranosyl)-(1→4)-2,3,6-tri-O-acetyl-β-D-glucopyranoside (14), which was deallylated, activated as an trichloroacetimidate, and coupled to 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (20). Several compounds were fully characterized by ¹H NMR spectroscopy. Deprotection furnished the monodeoxygenated tetrasaccharides 9 and 23.     

Synthesis of Four Spacer-Containing Trisaccharides with the 4-0-(β-L-Rhamnopyranosyl)-D-glucopyranose Unit in Common,Representing Fragments of Capsular Polysaccharides from Streptococcus Pneumoniae Types 2, 7F, 22F,and 23F

Abstract

The synthesis is reported of 3-aminopropyl 3-O-[4-O(β-L-rhamnopyranosyl)-β-D-glucopyranosyl]-α-L-rhamnopyranoside (34), 3-aminopropyl 2-acetamido-3-O-[4-0-(β-L-rhamnopyranosyl)-β-D-glucopyranosyl]-2-deoxy-β-D-galactopyranoside (37), 3-aminopropyl 3-O-[4-O-(β-L-rhamnopyranosyl)-α-D-glucopyranosyl]-α-D-galactofuranoside (41), and 3-aminopropyl 4-O-[4-O-(β-L-rhamnopyranosyl)-β-D-glucopyranosyl]-β-D-galactopyranoside (45). These are spacer-containing fragments of the capsular polysaccharides of Streptococcus pneumoniae type 2, 7F, 22F, and 23F, respectively, which are constituents of Pneumovax^© 23. 2,3,4-Tri-O-benzyl-α-L-rhamnopyranosyl bromide was coupled to l,6-anhydro-2,3-di-(O-benzyl-β-D-glucopyranose (3). Opening of the anhydro ring, removal of AcO-1, and imidation of l,6-anhydro-2,3-di- O-benzyl-4-O-(2,3,4-tri-O-benzyl-β-L-rhamnopyranosyl)-β-D-glucopyranose (4β) afforded 6-O-acetyl-2,3-di-O-ben-zyl-4-O-(2,3,4-tri- O-benzyl-β-L-rhamnopyranosyl)-αβ-D-glucopyranosyl trichloroacet-imidate (7αβ). Condensation of 7αβ with 3-N-benzyloxycarbonylaminopropyl 2-O-ben-zyl-5,6-O-isopropylidene-α-D-galactofuranoside (26), followed by deprotection gave 41 Opening of the anhydro ring of 4 p followed by debenzylation, acerylauon, removal of AcO-1, and imidation yielded 2,3,6-tri-(9-aceryl-4-O-(2,3,4-tri-0-acetyl-P-L-rharnnopyran-.-osyl)-α-D-glucopyranosyl trichloroacetimidate (11). Condensation of 11 with 3-N-bcn-zyloxycarbonylaminopropyl 2,4-di-O-benzyl-α-L-rhamnopyranoside (18), with 3-N-bcn-zyloxycarbonylaminopropyl 2-acetamido-4,6-O-benzylidene-2-deoxy-β-D-galactopyran-oside (21), or with 3-N -benzyloxycarbonylaminopropyl 2-O-acetyl-3-O-allyl-6-O-benzyl-β-D-galactopyranoside (31), followed by deprotection afforded 34, 37, and 45, respectively.     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT

The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained upon selective iodination of a tetrasaccharide diol.     

Displacement of Sugar Triflates with C-Nucleophiles: D-Glucopyranose and D-Ribofuranose Chain Extension and Functionalization

Treatment of methyl 4-O-benzyl-2,3-di-O-methoxymethyl-6-O-1-6-O-trifluoromethanesulfonyl-α -D-glucopyranoside 1 or 3-O-benzyl-1,2-O-isopropylidene-5-O-trifluoromethenesulfonyl-α-D-ribofuranoside 2 with a variety of functionalized C-nucleophiles in THF/HMPA leads to the corresponding chain-extended sugars in very good to excellent yields.     

The Synthesis of the 2′′- and 2′′′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2′′ or C-2′′′ have been synthesized in [2+2] block syntheses. O-(2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-3,6-di-O-benzyl-1,2-di-O-acetyl-β-D-glucopyranose (6), prepared from the respective orthoester, was coupled to the glycosyl acceptor 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside. In the resulting tetrasaccharide 8, the only ester group was removed and replaced by a xanthate which was reduced in a Barton-McCombie reaction to afford the 2′′-deoxygenated tetrasaccharide 12. For the synthesis of a 2′′′-deoxygenated derivative, a maltose building block was assembled from two monosaccharides. The key building block was ethyl 2,3,6-tri-O-benzyl-1-thio-β-D-glucopyranoside (14) which was used i) as a glycosyl acceptor in a phenylselenyl chloride mediated coupling reaction with tri-O-benzyl-glucal and ii) after the first coupling as a glycosyl donor to react with glycosyl acceptor 7 to give tetrasaccharide 18. The phenylselenyl group was reduced with tributyltin hydride on the disaccharide level. Deprotection of 18 furnished the 2′′′-deoxy-maltosyl-(1→4)-trehalose 20.     

Synthetic Studies on Sialoglycoconjugates 90: Total Synthesis of Sulfated Glucuronyl Paraglobosides

ABSTRACT

3-O-Sulfo glucuronyl paragloboside derivatives (pentasaccharides) have been synthesized. The important intermediate designed for a facile sulfation in the last step and effective, stereocontrolled glycosidation, methyl (4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-α-D-glucopyranosyl trichloroacetimidate)uronate (8) was prepared from methyl [2-(trimethylsilyl)ethyl β-D-glucopyranosid]uronate (3) via selective 4-O-acetylation, 2-O-benzoylation, 3-O-levulinoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation. The glycosylation of 8 with 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (9) using trimethylsilyl trifluoromethanesulfonate gave 2-(trimethylsilyl)ethyl O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (10), which was transformed via removal of the benzyl group, benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the disaccharide donor 13. On the other hand, 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (20) as the acceptor was prepared from 2-(trimethylsilyl)ethyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside (14) via O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, imidate formation, coupling with 2-(trimethylsilyl)ethyl O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (18), removal of the O-acetyl and N-phthaloyl group followed by N-acetylation. Condensation of 13 with 20 using trimethylsilyl trifluoromethanesulfonate afforded the desired pentasaccharide 21, which was transformed by removal of the benzyl group, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the pentasaccharide donor 24. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25) with 24 gave the desired β-glycoside 26, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation.     

Ring Opening of Benzyl β-D-Galactoside Cyclic Sulfates into Galactose Monosulfates. New Access to 6-Deoxy-Galacto-Hex-5-Enopyranoside and 4-Deoxy-3-Ketogalactopyranoside.

ABSTRACT

The behavior of 3,4- and 4,6-cyclic sulfates derived from benzyl 2,6- and 2,3-di-O-benzyl-β-D-galactopyranosides toward hydrolysis has been studied using aqueous sodium hydroxide under various conditions. Starting from benzyl 2,6-di-O-benzyl-3,4-O-sulfuryl-β-D-galactopyranoside (5), the reaction with aq NaOH in THF gave both 3- and 4-monosulfates 7 and 8 (83%, in 68:32 ratio), while the reaction in DMF led unexpectedly to the 4-deoxy-3-keto derivative 10 in 77% yield after acidic hydrolysis of the intermediate enolester 9. On the other hand, when benzyl 2,3-di-O-benzyl-4,6-O-sulfuryl-β-D-galactopyranoside (6) was treated with aq NaOH in THF, a mixture of benzyl 2,3-di-O-benzyl-6-deoxy-4-O-(sodium sulfonato)-α-L-arabino-hex-5-enopyranoside (11) and benzyl 2,3-di-O-benzyl-4-deoxy-6-O-(sodium sulfonato)-α-L-threo-hex-4-enopyranoside (12) (in 65:35 ratio) was obtained in 93% yield, giving a new and rapid access to 11, a potential precursor of L-sugars derivatives. Alternatively, BzONBu₄ gave a regiospecific opening reaction of 6 and led to the 6-O-benzoate 4-O-sulfate derivative (13) in excellent yield.     

Synthesis of a Single Repeat Unit of Type VIII Group B Streptococcus Capsular Polysaccharide 1

Abstract

We have synthesized a single repeat unit of type VIII Group B Streptococcus capsular polysaccharide, the structure of which is {L-Rhap(β1→4)-D-Glcp(β1→4)[Neu5Ac(α2→3)]-D-Galp(β→4)}_n. The synthesis presented three significant synthetic challenges namely: the L-Rhap(β→4)-D-Glcp bond, the Neu5Ac(α2→3)-D-Galp bond and 3,4-D-Galp branching. The L-Rhap bond was constructed in 60% yield (α:β 1:1.2) using 4-O-acetyl-2,3-di-O-benzoyl-α-L-rhamnopyranosyl bromide 6 as donor, silver silicate as promotor and 6-O-benzyl-2,3-di-O-benzoyl-1-thio-β-D-glucopyranoside as acceptor to yield disaccharide 18. The Neu5Ac(α2→3) linkage was synthesized in 66% yield using methyl [phenyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-nonulopyranosid]onate as donor and triol 2-(trimethylsilyl) ethyl 6-O-benzyl-β-D-galactopyranoside as acceptor to give disaccharide 21. The 3,4-D-Galp branching was achieved by regioselective glycosylation of disaccharide diol 21 by disaccharide 18 in 28% yield to give protected tetrasaccharide 22. Tetrasaccharide 22 was deprotected to give as its 2-(trimethylsilyl)ethyl glycoside the title compound 1a. In addition the 2-(trimethylsilyl)ethyl group was cleaved and the tetrasaccharide coupled by glycosylation (via tetrasaccharide trichloroacetimidate) to a linker suitable for conjugation.

     

Accessibility of D-Mannopyranoside Glycosylating Synthons by Acetolysis for Preparations of Oligosaccharide Moieties of N-Linked Glycoproteins

Abstract

Selective acetolysis of methyl 2, 3, 4, 6-tetra-O-benzyl-α-D-manno-pyranoside (2) allows for easy preparation of 1-acetates of 2, 3,4, 6-tetra-O-benzyl (5), 6-O-acetyl-2, 3, 4, tri-O-benzyl-(6), 4, 6-di-O-acetyl-2,3-di-O-benzyl-(7), 3, 4, 6-tri-O-acetyl-2-O-benzyl-(8), and 2, 4, 6-tri-O-acetyl-3-O-benzyl-D-mannopyranoside (9). 8 and 9 formed are separated by preparative HPLC in 30-60g scale. The time course of previously described acetolyses of 3, 4, 6-tri-O-benzyl- 1, 2-O-(1-methoxyethyidene)-β-D-mannopyranose (3), and methyl 2, 3-dt-O-benzyl-4, 6-O-benzylldene-α-D-mannopyranoside (4) giving 9, 1, 2, 6-tri-O-acetyl-3, 4-di-O-benzyl-(10), and 1, 2-di-O-acetyl-3, 4, 6-tri-O-benzyl-(11) α-D-mannopyranose as well 7 have been studied.     

Synthetic Studies on Sialoglycoconjugates 95: Total Synthesis of Sulfated Glucuronyl Lactosaminyl Paraglobosides

ABSTRACT

3-O-Sulfo glucuronyl neolactohexanosyl ceramide derivatives (heptasaccharides) have been synthesized. Condensation of 2-(trimethylsilyl)ethyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl trichloroacetimidate (1) gave the desired β-glycoside 3, which was converted into 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (4) via removal of the O-acetyl and N-phthaloyl groups, followed by N-acetylation. Glycosylation of 4 with O-(methyl 4-O-acetyl-2-O-benzoyl-3-O-levulinoyl-β-D-glucopyranosyluronate)-(1→3)-2,4,6-tri-O-benzoyl-α-D-galactopyranosyl trichloroacetimidate (5) using trimethylsilyl trifluoromethanesulfonate gave the target tetrasaccharide 6, which was transformed via removal of the benzyl group, O-benzoylation, removal of the 2-(trimethylsilyl)ethyl group and imidate formation into the tetrasaccharide donor 9. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-(1→3)-O-(2,4,6-tri-O-benzyl-β-D-galactopyranosyl)-(1→4)-2,3,6-tri-O-benzyl-β-D-glucopyranoside (10) with the imidate donor 9 using trimethylsilyl trifluoromethanesulfonate gave the desired heptasaccharide 11, which was transformed into the heptasaccharide imidate donor 14. Glycosylation of (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (15) with 14 gave β-glycoside 16, which was transformed into the four target compounds, via reduction of the azido group, coupling with octadecanoic acid or tetracosanoic acid, selective removal of the levulinoyl group, O-sulfation, hydrolysis of the methyl ester group and O-deacylation.     

Synthesis of Rhamnogalacturonan I Fragments

ABSTRACT

The partially deprotected trisaccharide 17 has been synthesized as an analogue of the repeating unit of the backbone of rhamnogalacturonan I. The trisaccharide 17 was obtained after prior selective derivatization of HO-3 and HO-4 of a rhamnopyranose cyanoethylidene glycosyl donor, followed by coupling with a tritylated galactopyranosyluronic acceptor (11), selective removal of the acetyl group at the O-2' position of the formed disaccharide 12, and glycosylation of the HO-2' position with methyl (ethyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-1-thio-β-D-galactopyranosid)uronate (14) providing methyl (methyl 2,3-di-O-benzyl-4-O-p-methoxybenzyl-α-D-galactopyranosyluronate)-(1→2)-(4-O-benzoyl-3-O-benzyl-α-L-rhamnopyranosyl)-(1→4)-(allyl 2,3-di-O-benzyl-β-D-galactopyranosid)uronate (15). Finally, palladium chloride catalyzed deallylation (16) and hydrogenolysis over Pd-C resulted in methyl (methyl α-D-galactopyranosyluronate)-(1→2)-(4-O-benzoyl-α-L-rhamnopyranosyl)-(1→4)-α/β D-galactopyranuronate (17).     

BLOCK SYNTHESIS WITH GALACTURONATE TRICHLOROACETIMIDATES[1]

The disaccharide methyl (4-O-benzoyl-3-O-benzyl-2-O-acetyl-α-L-rhamno pyranosyl)-(1→4)-(allyl 2,3-di-O-benzyl-β-D-galactopyranosid)uronate (13) was obtained in an excellent yield of 88% using methyl (allyl 2,3-di-O-benzyl-β-D-galactopyranosid)uronate ((12) as the glycosyl acceptor and a slight excess of the 1,2-di-O-acetyl-rhamnoglycosyl donor 5a. Disaccharide 13 is a key intermediate that can be used either as a glycosyl acceptor or glycosyl donor for the preparation of rhamnogalacturonan fragments. Here, introduction of the trichloroacetimidate function at the anomeric center gave the disaccharide glycosyl donor 28, which could be applied in a blockwise glycosylation reaction to form the L-Rha-α(1→4)-D-GalA-α(1→4)-D-GalA trisaccharide 29. Generally, on condition that no neighboring group effect influenced the reaction at the anomeric center of the α-trichloroacetimidate galacturonate glycosyl donors (20–22, 28), α-glycosidic linkages were nearly exclusively formed, except in the case of the 4-O-methylgalactopyranosyluronate 22.     

Synthesis of Tetrasaccharide Repeating Unit of the K-Antigen from Klebsiella Type-16

Abstract

Starting from L-fucose, D-glucose and lactose, methyl O-[2,3-di-O-benzoyl-4, 6-O-(4-methoxybenzylidene)-β-D-glucopyranosyl]-(1→4)-2,3-di-O-benzoyl-α-L-fucopyranoside and methyl O-(2,3,4,6-tetra-O-benzyl-β-D-galactopyranosyl)-(1→4)-O-(2,3,6-tri-O-benzyl-α-D-glucopyranosyl)-(1→4)-O-(methyl 2,3-di-O-benzoyl-β-D-glucopyranosyluronate)-(1→4)-2,3-di-O-benzoyl-α-L-fucopyranoside were synthesized. Removal of protecting groups gave the tetrasaccharide repeating unit of the antigen from Klebsiella type-16 in the form of its methyl ester methyl glycoside.     

Iodonium-Ion Assisted Stereospecific Glycosylation: Synthesis of Oligosaccharides Containing α(1-4)-Linked L-Fucopyranosyl Units

ABSTRACT

The terminal glycosyl acceptor methyl 2,3-di-O-benzyl-α-L-fucopyranoside (6) was extended three times with the non-terminal glycosyl donor ethyl 4-O-acetyl-2,3-di-O-benzyl-1-thio-ß-L-fucopyranoside (13) via iodonium-ion assisted glycosylations and intermittent removal of the C-4 acetyl group in intermediate dimer 16 and trimer 18. The 4-O-acetyl group in trimer 18 and tetramer 20 was highly resistant towards basic hydrolysis. The latter could be nullified by using dichloroacetyl instead of acetyl to protect the C-4-OH in the donor. The exclusive formation of 1,2-cis-linked oligomers could be explained by through-bond interactions exerted by the electron-withdrawing C-4 acyl group in the glycosyl donor.     

Application of Phenyl 1-Selenoglycosides in the Synthesis of a Cell-Wall Tetrameric Fragment of Proteus Vulgaris Strain 5/43

Abstract

DAST-assisted rearrangement of 3-O-allyl-4-O-benzyl-α-l-rhamnopyranosyl azide followed by treatment of the generated fluorides with ethanethiol and BF₃·OEt₂ gave glycosyl donor ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside. Stereoselective glycosylation of methyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside with ethyl 3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-1-thio-α/β-l-glucopyranoside, under the agency of NIS/TfOH afforded methyl 3-O-(3-O-allyl-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzyli-dene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Removal of the allyl function of the latter dimer, followed by condensation with properly protected 2-azido-2-deoxy-glucosyl donors, in the presence of suitable promoters, yielded selectively methyl 3-O-(3-O-[6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-α-D-glucopyranosyl]-2-azido-4-O-benzyl-2,6-dideoxy-α-l-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-glucopyranoside. Deacetylation and subsequent glycosylation of the free HO-6 with phenyl 2,3,4,6-tetra-O-benzoyl-1-seleno-β-D-glucopyranoside in the presence of NIS/TfOH furnished a fully protected tetrasaccharide. Deprotection then gave methyl 3-O-(3-O-[6-O-{β-D-glucopyranosyl}-2-acetamido-2-deoxy-β-D-glucopyranosyl)-2-acetamido-2,6-dideoxy-α-L-glucopyranosyl)-2-acetamido-2-deoxy-β-D-glucopyranoside.     

Preparation of trans Diequatorial 2,3-Pyruvate Acetals in a Di- and a Trisaccharide Related to the K-Antigen from E. Coli 0101:K103:H−

Abstract

Using methyl 2,2-bis(ethylthio)propionate as acetalating agent and triflic acid-sulfuryl chloride as catalyst, synthesis of 2,3-trans diequatorial pyruvate ketal was achieved. Starting from D-galactose and L-rhamnose derivatives, methyl 2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl-(1→4)-6-O-benzyl-2,3-O-(1-methoxycarbonyl)ethylidene- α-D-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside and methyl 4,6-di-O-benzyl-2,3-O-(1-methoxy-carbonyl)ethylidene-α-D-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-L-rhamnopyranoside were synthesized. Removal of the protecting groups from the former, afforded the trisaccharide repeating unit of the K-antigen from E.coli O101:K103:H^? in the form of its methyl glycoside methyl ester.     

Syntheses of Methyl 2-O-, 3-O- and 6-O-(2′-Hydroxypropyl)-α-D-Glucopyranosides 1

Abstract

Methyl 6-O-, 3-O- and 2-O-(2′-hydroxypropyl)-α-D-glucopyranosides (4,8, and 12) were synthesized starting from methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside (1), methyl 4,6-O-benzylidene-α-D-glucopyranoside (5), and methyl 3-O-benzyl-4,6-O-benzylidene-D-glucopyranoside (9), respectively. Overall yields were 88%, 6% and 26% of 4, 8 and 12, respectively, with the 2-ether (12) being crystalline and the 3-ether (8) a single diastereomer.