Regioselective synthesis of a glycomimetic trisaccharide of Sialyl Lewis (sLe)

Sialyl Lewis (sLe^x) is the smallest naturally occurring carbohydrate ligand that binds to E-Selectin on the activated endothelium. We report here the total synthesis of acetic acid-sLe^x analog (12), for testing as a therapeutic agent. Methoxyethyl 4-O-(3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (3) was prepared starting from the methoxyethyl-β-d-lactoside (2), which was selectively benzoylated to give the methoxyethyl 2,6-di-O-benzoyl-4-O-(2,6-di-O-benzoyl-3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (4). Glycosylation of acceptor 4 with methyl 2,3,4-tri-O-benzyl-1-thio-β-l-fucopyranoside (5) in the presence of cupric bromide and tetrabutylammonium bromide afforded the corresponding methoxyethyl 2,6-di-O-benzyl-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-4-O-(2,6-di-O-benzyl-3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (6). Selective removal of the 4″,6″-O-isopropylidene group from 6 gave the deprotected trisaccharide 7. The regioselective esterification of O-3″ of trisaccharide 8 (obtained from the dibutylstannylene derivative of 7) with benzyl-2-bromoacetate and tetrabutylammonium bromide afforded the 3″-O-carbobenzyloxymethyl trisaccharide derivative 9, which on saponification and hydrogenolysis with palladium-charcoal afforded the target trisaccharide 12 glycomimetic of Sialyl Lewis (sLe^x) trisaccharide omitting the sialic acid moiety.     

Synthesis of phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside and related compounds

The reaction of phenyl 2-acetamido-2-deoxy-4,6- O-(p-methoxybenzylidene)-β-d-glucopyranoside with 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide under halide ion-catalyzed conditions proceeded readily, to give phenyl 2-acetamido-2-deoxy-4,6-O-(p-methoxybenzylidene)-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d-glucopyranoside (8). Mild treatment of 8 with acid, followed by hydrogenolysis, provided the disaccharide phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside. Starting from 6-(trifluoroacetamido)hexyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranoside, the synthesis of 6-(trifluoroacetamido)hexyl 2-acetamido-2-deoxy-3-O-β-l-fucopyranosyl-β-d-glucopyranoside has been accomplished by a similar reaction-sequence. On acetolysis, methyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-α-d-glucopyranoside gave 2-methyl-[4,6-di-O-acetyl-1,2-dideoxy-3-O-(2,3,4-tri-O-acetyl-α-l-fucopyranosyl)-α-d-glucopyrano]-[2, 1-d]-2-oxazoline as the major product.     

Silylmethylene radical cyclization. A stereoselective approach to branched sugars

Ethyl 6-O-benzyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranoside (2) was converted, in three steps and in 73% overall yield, into ethyl 6-O-benzyl-2,3-dideoxy-3-C-(hydroxymethyl)-α-d-ribo-hex-2-enopyranoside. This transformation involved silylation of 2 with (bromomethyl)chlorodimethylsilane and application of the Nishiyama-Stork radical cyclisation, followed by Tamao oxidation of the sila cycle. Ethyl 6-O-benzyl-2,3-dideoxy-α-d-threo-hex-2-enopyranoside and benzyl 2,6-di-O-benzyl-α-l-threo-hex-4-enopyranoside were similarly transformed into, respectively, ethyl 6-O-benzyl-2,3-dideoxy-3-C-(hydroxymethyl)-α-d-lyxo-hex-2-enopyranoside (50%), and benzyl 2,6-di-O-benzyl-4-deoxy-4-C-(hydroxymethyl)-β-d-galactopyranoside (71%).     

New triterpenoid saponins from Patrinia scabiosaefolia

Phytochemical investigation of the methanol extract from the whole plants of Patrinia scabiosaefolia Fisch. resulted in the isolation of four new triterpenoid saponins (1–4) along with six known compounds (5–10). On the basis of spectroscopic and chemical methods, the structures of the new compounds were established as 3-O-β-d-xylopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-12β,30-dihydroxy-olean-28,13β-olide (1), 3-O-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-12β,30-dihydroxy-olean-28,13β-olide (2), 3-O-β-d-xylopyranosyl-(1→2)-β-d-glucopyranosyl-12β, 30-dihydroxy-olean-28,13β-olide (3), and 3-O-β-d-glucopyranosyl-(1→4)-β-d-xylopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl-oleanolic acid 28-O-β-d-glucopyranoside (4), respectively. Compounds 1–3 possess a novel 12β,30-dihydroxy-olean-28,13β-lactone aglycone and a 12β-hydroxy substituent that is rarely found in this kind of triterpenoid saponin.     

Electron-impact mass spectrometry of methyl O-methylglucopyranosiduranamides

6-O-Acetyl-2,4-diazido-3-O-benzyl-2,4-dideoxy-β-D-glucopyranosyl chloride and 2,6-diazido-3,4-di-O-benzyl-2,6-dideoxy-β-D-glucopyranosyl chloride are two valuable building units suitable for the synthesis of α-linked disaccharides containing 2,4-diamino-2,4-dideoxy- or 2,6-diamino-2,6-dideoxy-D-glucose as nonreducing moieties. The glycoside synthesis is accomplished stereoselectively under mild conditions in the presence of silver perchlorate. The α-(1→3)-linked disaccharides 2,4-diacetamido-2,4-dideoxy-3-O-(2,4-diacetamido-2,4-dideoxy-α-D-glucopyranosyl)-D-glucopyranose and 2-acetamido-2-deoxy-3-O-(2,6-diacetamido-2,6-dideoxy-α-D-glucopyranosyl)-D-glucopyranose have been prepared.     

Studies on the stereoselective synthesis of a protected α-d-Gal-(1→2)-d-Glc fragment

A novel 1,2-cis stereoselective synthesis of protected α-d-Gal-(1→2)-d-Glc fragments was developed. Methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-α-d-glucopyranoside (13), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-α-d-glucopyranoside (15), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-β-d-glucopyranoside (17), and methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-β-d-glucopyranoside (19) were favorably obtained by coupling a new donor, isopropyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-1-thio-β-d-galactopyranoside (2), with acceptors, methyl 3-O-benzoyl-4,6-O-benzylidene-α-d-glucopyranoside (4), methyl 3,4,6-tri-O-benzoyl-α-d-glucopyranoside (5), methyl 3-O-benzoyl-4,6-O-benzylidene-β-d-glucopyranoside (8), and methyl 3,4,6-tri-O-benzoyl-β-d-glucopyranoside (12), respectively. By virtue of the concerted 1,2-cis α-directing action induced by the 3-O-allyl and 4,6-O-benzylidene groups in donor 2 with a C-2 acetyl group capable of neighboring-group participation, the couplings were achieved with a high degree of α selectivity. In particular, higher α/β stereoselective galactosylation (5.0:1.0) was noted in the case of the coupling of donor 2 with acceptor 12 having a β-CH₃ at C-1 and benzoyl groups at C-4 and C-6.     

Synthesis of a novel pentasaccharide core component from the lipooligosaccharide of Moraxella catarrhalis

The novel pentasaccharide [p-(trifluoroacetamido)phenyl]ethyl 3-O-β-d-glucopyranosyl-4-O-β-d-glucopyranosyl-6-O-[2-O-(α-d-glucopyranosyl)-β-d-glucopyranosyl]-α-d-glucopyranoside (1), which includes a linker moiety to enable facile coupling to an antigenic protein, was synthesised as a component of a potential vaccine candidate against the Gram-negative bacterium Moraxella catarrhalis. This microorganism is one of three principal causative agents of otitis media in children. The pentasaccharide represents a common cross-serotype (A, B and C) structure from the lipooligosaccharides of Moraxella catarrhalis.     

The synthesis and properties of benzylated oxazolines derived from 2-acetamido-2-deoxy-D-glucose

2-Methyl-(2-acetamido-3,4,6-tri-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline,2-methyl-(2-acetamido-6-O-acetyl-3,4-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline,and 2-methyl-(2-acetamido-4-O-acetyl-3,6-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline were synthesized from the allyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranosides, and from the 3,4-di-O-benzyl or 3,6-di-O-benzyl analogs, respectively, both the α and β anomer being used in each case. The preparation of allyl 2-acetamido-3,4,6-tri-O-benzyl- and 3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside is also described. Treatment of the tri-O-benzyl oxazoline with dibenzyl phosphate gave a pentabenzylglycosyl phosphate, from which all the benzyl groups were removed by catalytic hydrogenation, giving 2-acetamido-2-deoxy-α-D-glucopyranosyl phosphate. The corresponding β anomer was not detectable. Treatment of the 3,4-, or 3,6-, di-O-benzyl oxazoline with allyl 2-acetamido-3,4-di-O-benzyl-α-D-glucopyranoside readily gave disaccharide products from which the protecting groups were removed, to give the (1→6)-linked isomer of di-N-acetylchitobiose. Under both acidic and basic conditions, this isomer was less stable than the (1→4)-linked compound.Attempts to employ the 3,6-di-O-benzyl oxazoline for the formation of (1→4)-linked disaccharides, by treatment with either anomer of allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-D-glucopyranoside, were not very successful, presumably owing to hindrance by the bulky benzyl groups.     

Synthesis of three oligosaccharides that form part of the complex type of carbohydrate moiety of glycoproteins

Silver trifluoromethanesulfonate-promoted condensation of 3,4,6-tri-O-acetyl-2-deoxy-phthalimido-β-d-glucopyranosyl bromide with benzyl 3,6-di-O-benzyl-α-d-mannopyranoside and benzyl 3,4-di-O-benzyl-α-d-mannopyranoside gave the protected 2,4- and 2,6-linked trisaccharides in yields of 54 and 32%, respectively. After exchanging the 2-deoxy-2-phthalimido groups for 2-acetamido-2-deoxy groups and de-blocking, the trisaccharides 2,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-mannose and 2,6-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-mannose were obtained. Similar condensation of 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d-glucopyranosyl bromide with benzyl 3,4-di-O-benzyl-α-d-mannopyranoside gave a pentasaccharide derivative in 52% yield. After transformations analogous to those applied to the trisaccharides, 2,6-di-O-[β-d-galactopyranosyl-(1→4)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)]-d-mannose was obtained.     

A synthesis of psi-cytidine

2-O-Benzoyl-3,6-di-O-benzyl-4-O-(chloroacetyl)-, 4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-, and 2-O-benzoyl-3,4,6-tri-O-benzyl-α-d-galactopyranosyl chloride were converted into the corresponding 2,2,2-trifluoroethanesulfonates, and these were treated with allyl 2-O-benzoyl-3,6-di-O-benzyl-α-d-galactopyranoside, to give allyl 2-O-benzoyl-4-O-[2-O-benzoyl-3,6-di-O-benzyl-4-O-(chloroacetyl)-β-d-galactopyranosyl]-3,6-di-O-benzyl- α-d-galactopyranoside (26; 41% yield), allyl 4-O-(4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-β-d-galactopyranosyl)-2-O-benzoyl-3,6-di-O-benzyl- α-d-galactopyranoside (27; 62% yield), and allyl 2-O-benzoyl-4-O-(2-O-benzoyl-3,4,6-tri-O-benzyl-β-d-galactopyranosyl)-3,6-di-O-benzyl-α-d-galactopyranoside (28; 65% yield). All disaccharides were free from their α anomers. Disaccharides 26 and 27 were found to be base-sensitive, and were de-esterified by KCN in aqueous ethanol, and debenzylated with H₂-Pd. Attempts to produce (1→4)-β-d-galactopyranosides from the coupling of a number of fully esterified d-galactopyranosyl sulfonates to allyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside were unsuccessful.     

Synthesis of 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d-glucopyranosyl chloride

A lactosaminyl donor, 3,6-di-O-acetyl-2-deoxy-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d- glucopyranosyl chloride, was synthesized in 10 steps, starting from 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranose. Benzyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside was prepared by regioselective benzylation at the primary hydroxyl group by the stannyl method, and was used as a key intermediate.

     

Triterpene saponins from Salsola imbricata

Continuing our investigations on medicinal plants of the Egyptian desert, two new triterpene glycoside derivatives, along with three known compounds have been isolated from the roots of Salsola imbricata, a shrub widely growing in Egypt. Their structures have been established as 3-O-β-d-xylopyranosyl-(1 → 2)-O-β-d-glucuronopyranosyl-akebonic acid 28-O-β-d-glucopyranoside and 3-O-β-d-xylopyranosyl-(1 → 2)-O-β-d-glucuronopyranosyl-29-hydroxyoleanolic acid 28-O-β-d-glucopyranoside on the basis of spectroscopic methods including 1D- (¹H, ¹³C) and 2D-NMR (DQF-COSY, HSQC, HMBC) experiments as well as mass spectrometry analysis.     

A furan-2-carbonyl C-glucoside and an alkyl glucoside from the parasitic plant,Dendrophthoe pentandra

A new furan-2-carbonyl C-(6′-O-galloyl)-β-glucopyranoside (scleropentaside F, 1) and a new alkyl glucoside [butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside, 2] were isolated from the entire hemi-parasitic plant, Dendrophthoe pentandra growing on Tectona grandis together with ten known compounds including, benzyl-O-β-d-glucopyranoside (3), benzyl-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside (4), benzyl-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranoside (5), methyl gallate 3-O-β-d-glucopyranoside (6), methyl gallate 3-O-(6′-O-galloyl)-β-d-glucopyranoside (7), (+)-catechin (8), procyanidin B-1 (9) and procyanidin B-3 (10), bridelionoside A (11), and kiwiionoside (12). In addition, compounds 1, 3–9 were isolated from this species growing on the different host, Mangifera indica. The structure elucidations were based on physical data and spectroscopic evidence including 1D and 2D experiments.     

Synthesis and characterization of propyl O-β-d-galactopyranosyl-(1→4)-O-β-d-galactopyranosyl-(1→4)-α-d-galactopyranoside

Allyl 4-O-(4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-β-d-galactopyranosyl)-2-O-benzoyl-3,6-di-O-benzyl-α-d- galactopyranoside was O-deallylated to give the 1-hydroxy derivative, and this was converted into the corresponding 1-O-(N-phenylcarbamoyl) derivative, treatment of which with dry HCl produced the α-d-galactopyranosyl chloride. This was converted into the corresponding 2,2,2-trifluoroethanesulfonate, which was coupled to allyl 2-O-benzoyl-3,6-di-O-benzyl-α-d-galactopyranoside, to give crystalline allyl 4-O-[4-O-(4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-β-d-galactopyranosyl)-2-O-benzoyl-3,6-di- O-benzyl-β-d-galactopyranosyl]-2-O-benzoyl-3,6-di-O-benzyl-α-d-galactopyranoside (15) in 85% yield, no trace of the α anomer being found. The trisaccharide derivative 15 was de-esterified with 2% KCN in 95% ethanol, and the product O-debenzylated with H₂-Pd, to give the unprotected trisaccharide. Alternative sequences are discussed.     

Synthetic mucin fragments. Methyl 6-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,methyl 3,4-di-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,and methyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1 å 3)-O-β-D-galactopyranosyl-(1 å 3)-O-(2-acetamido-2-deoxy-β- D-glucopyranosyl)-(1 å 3)-β-D-galactopyranoside

Condensation of methyl 2,6-di-O-benzyl-β-d-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)-[2,1,-d]-2-oxazoline (1) in 1,2-dichloroethane, in the presence of p-toluenesulfonic acid, afforded a trisaccharide derivative which, on deacetylation, gave methyl 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2,6-di-O-benzyl-β-d- glactopyranoside (5). Hydrogenolysis of the benzyl groups of 5 furnished the title trisaccharide (6). A similar condensation of methyl 2,3-di-O-benzyl-β-d-galactopyranoside with 1 produced a partially-protected disacchraide derivative, which, on O-deacetylation followed by hydrogenolysis, gave methyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-glactopyranoside (10). Condensation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-benzyl-β-d- galactopyranoside with 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of powdered mercuric cyanide gave a fully-protected tetrasaccharide derivative, which was O-deacetylated and then subjected to catalytic hydrogenation to furnish methyl O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-O-β-d-galactopyranosyl-(1å3)-O-(2-acetamido-2-deoxy- β-d-glucopyranosyl)-(1å3)-β-d-galactopyranoside (15). The structures of 6, 10, and 15 were established by ¹³C-n.m.r. spectroscopy.     

Synthesis of octyl S-glycosides of tri- to pentasaccharide fragments related to the GPI anchor of Trypanosoma brucei

The three oligosaccharide octyl-S-glycosides Man-α1,6-Man-α1,4-GlcNH₂-α1,S-Octyl (19), Man-α1,6-(Gal-α1,3)Man-α1,4-GlcNH₂-α1,S-Octyl (27) and Man-α1,2-Man-α1,6-(Gal-α1,3)Man-α1,4-GlcNH₂-α1,S-Octyl (37), related to the GPI anchor of Trypanosoma brucei were prepared by a stepwise and block-wise approach from octyl 2-azido-2-deoxy-3,6-di-O-benzyl-1-thio-α-d-glucopyranoside (8) and octyl 2-O-benzoyl-4,6-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-1-thio-α-d-mannopyransoside (9). Glucosamine derivative 8 was obtained from 1,3,4,6-tetra-O-acetyl-2-azido-2-desoxy-β-d-glucopyranose (1) in five steps. Mannoside 9 was converted into the corresponding imidate 12 and coupled with 8 to give disaccharide octyl-S-glycoside 13 which was further mannosylated to afford trisaccharide 19 upon deprotection. Likewise, mannoside 9 was galactosylated, converted into the corresponding imidate and coupled with 8 to give trisaccharide 25. Mannosylation of the latter afforded tetrasaccharide 27 upon deprotection. Condensation of 25 with disaccharide imidate 35 gave, upon deprotection of the intermediates, the corresponding pentasaccharide octyl-S-glycoside 37. Saccharides 19, 27 and 37 are suitable substrates for studying the enzymatic glycosylation pattern of the GPI anchor of T. brucei.     

Two new flavonol glycosides from the leaves of Cleome viscosa L.

From the leaves of Cleome viscosa L., two new flavonol glycosides, named visconoside A (1) and visconoside B (2), together with six known flavonol glycosides, vincetoxicoside A (3), vincetoxicoside B (4), kaempferitrin (5), kaempferide 3-O-β-d-glucopyranoside 7-O-α-l-rhamnopyranoside (6), kaempferol 3-O-β-d-glucopyranoside 7-O-α-l-rhamnopyranoside (7), and isorhamnetin 3-O-β-d-glucopyranoside (8) were isolated by various chromatography methods. Its chemical structure was elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and compared with literatures.     

Synthesis of 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses

Five 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses (lipophilic, muramoyl dipeptide analogs) were synthesized from benzyl 2-(benzyloxycarbonylamino)-3-O-(d-1-carboxyethyl)-2-deoxy-5,6-O-isopropylidene-β-dglucopyranoside (1). Methanesulfonylation of 3, derived from the methyl ester of 1 by O-deisopropylidenation, gave the 6-methanesulfonate (4). (Tetrahydropyran-2-yl)ation of 4 gave benzyl 2-(benzyloxycarbonylamino)-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-6-O-(methylsulfonyl)-5-O-(tetrahydropyran-2-yl)-β-d- glucofuranoside, which was treated with sodium azide to give the corresponding 6-azido derivative (6). Condensation of benzyl 6-amino-2-(benzyloxycarbonyl-amino)-2,6-dideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-5-O-(tetrahydropyran-2-yl)-β-d-glucofuranoside, derived from 6 by reduction, with the activated esters of octanoic, hexadecanoic, and eicosanoic acid gave the corresponding 6-N-fatty acyl derivatives (8–10). Coupling of the 2-amino derivatives, obtained from compounds 8, 9, and 10 by catalytic reduction, with the activated esters of the fatty acids, gave the 2,6-(diacylamino)-2,6-dideoxy derivatives (11–15). Condensation of the acids, formed from 11–15 by de-esterification, with the benzyl ester of l-alanyl-d-isoglutamine, and subsequent hydrolysis, afforded benzyl 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine benzyl ester)-β-d-glucofuranosides. Hydrogenation of the dipeptide derivatives thus obtained gave the five lipophilic analogs of 6-amino-6-deoxymuramoyl dipeptide, respectively, in good yields.     

The synthesis of O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→4)-N-acetylnormuramoyl-l-α-aminobutanoyl-d-isoglutamine

Benzyl 2-acetamido-3-O-allyl-6-O-benzyl-2-deoxy-4-O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)- α-d-glucopyranoside (4) was obtained in high yield on using the silver triflate method in the absence of base. Compound 4 was converted in six steps into benzyl 2-acetamido-4-O-(2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-β-d-glucopyranosyl)-6-O-benzyl-3-O-(carboxymethyl)-2-deoxy-α-d- glucopyranoside, which was coupled with the benzyl ester of l-α-aminobutanoyl-d-isoglutamine and the product hydrogenolyzed to afford the title compound. O-Benzylation of benzyl 2-acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-3-O-allyl-6-O-benzyl-2-deoxy-α-d-glucopyranoside with benzyl bromide and barium hydroxide in N,N-dimethylformamide is strongly exhanced by sonication of the reaction mixture.     

Synthesis of 2,4-diacetamido-2,4,6-trideoxy-D-Galactose

Treatment of benzyl 2-acetamido-3-O-benzyl-2,6-dideoxy-4-O-(methylsulfonyl)-α-D-glucopyranoside (1) with sodium azide in hexamethylphosphoric triamide gave the 4-azido-α-D-galacto derivative (2), which was converted into benzyl 2,4-di-acetamido-3-O-benzyl-2,3,6-trideoxy-α-D-galactopyranoside (3) by hydrogenation and subsequent acetylation. Hydrogenolysis of 3 at atmospheric pressure afforded benzyl 2,4-diacetamido-2,4,6-tridcoxy-α-D-galactopyranoside (4), which was acetylated to give the 3-O-acetyl derivative (5). The n.m.r. spectrum of 5 was in agreement with the assigned structure and different from that of benzyl 2,4-di-acetamido-3-O-acetyl-α-D-glucopyranoside (9), which was prepared from the known benzyl 2,4-diacetamido-3-O-benzyl-2,4,6-trideoxy-α-D-glucopyranoside. Catalytic hydrogenolysis of 4 gave 2,4-diacetamido-2,4,6-trideoxy-D-galactose (6).