The deamination of methyl 5-amino-5,6-dideoxy-2,3-O-isopropylidene-α-L-talo- and -β-D-allo-furanoside with nitrous acid

Deamination of methyl 5-amino-5,6-dideoxy-2,3-O-isopropylidene-α-L-talofuranoside (6) with sodium nitrite in 90% acetic acid at ≈0° gave methyl 6-deoxy-2,3-O-isopropylidene-α-L-talofuranoside (8a) and methyl 6-deoxy-2,3-O-isopropylidene-β-D-allofuranoside (9a) (combined yield, 12.3%), the corresponding 5-acetates 8b (2.9%) and 9b (26.4%), and the unsaturated sugar methyl 5,6-dideoxy-2,3-O-isopropylidene-β-D-ribo-hex-5-enofuranoside (10) (43.5%). Similar deamination of methyl 5-amino-5,6-dideoxy-2,3-O-isopropylidene-β-D-allofuranoside (7) gave 8a and 9a (combined yield, 20.4%), 8b (12.5%), 9b (25.8%), 10 (7.7%), and the rearranged products 6-deoxy-2,3-O-isopropylidene-5-O-methyl-L-talofuranose (13a, 17.5%) and the corresponding 1-acetate 13b (14.1%). A synthesis of 13a was accomplished by successive methylation and debenzylation of the conveniently prepared benzyl 6-deoxy-2,3-O-isopropylidene-α-L-talofuranoside (15b). Differences between the two sets of deamination products can be rationalized by assuming that the carbonium-ion intermediate reacts in the initial conformation assumed, before significant interconversion to other conformations occurs.     

Synthesis of acetylenic sugars and uronic acids via two-carbon chain extension of d-ribose

Treatment of methyl β-d-ribofuranoside with acetone gave methyl 2,3-O-isopropylidene-β-d-ribofuranoside (1, 90%), whereas methyl α-d-ribofuranoside gave a mixture (30%) of 1 and methyl 2,3-O-isopropylidene-α-d-ribofuranoside (1a). On oxidation, 1 gave methyl 2,3-O-isopropylidene-β-d-ribo-pentodialdo-1,4-furanoside (2), whereas no similar product was obtained on oxidation of 1a. Ethynylmagnesium bromide reacted with 2 in dry tetrahydrofuran to give a 1:1 mixture (95%) of methyl 6,7-dideoxy-2,3-O-isopropylidene-β-d-allo- (3) and -α-l-talo-hept-6-ynofuranoside (4). Ozonolysis of 3 and 4 in dichloromethane gave the corresponding d-allo- and l-talo-uronic acids, characterized as their methyl esters (5 and 6) and 5-O-formyl methyl esters (5a and 6a). Ozonolysis in methanol gave a mixture of the free uronic acid and the methyl ester, and only a small proportion of the 5-O-formyl methyl ester. Malonic acid reacted with 2 to give methyl 5,6-dideoxy-2,3-O-isopropylidene-β-d-ribo-trans-hept-5-enofuranosiduronic acid (7).     

Synthesis of 3-amino-2,3,6-trideoxy-d-ribo- and -l-lyxo-hexofuranoses suitable for nucleoside synthesis

N-Acetylepidaunosamine (3-acetamido-2,3,6-trideoxy-d-ribo-hexopyranose) was converted into the diethyl dithioacetal and this was cyclized with HgCi₂, HgO, and MeOH, to give methyl 3-acetamido-2,3,6-trideoxy-α- and -β-d-ribo-hexofuranoside (4 and 5). These anomers were acetylated or (p-nitrobenzoyl)ated, and the esters were subjected to acetolysis, to afford 3-acetamido-1,5-di-O-acetyl-2,3,6-trideoxy-d-ribo-hexofuranose and 3-acetamido-1-O-acetyl-2,3,6-trideoxy-5-O-(p-nitrobenzoyl)-d-ribo-hexofuranose, respectively. Alternatively, compounds 4 and 5 were hydrolyzed to the free bases with barium hydroxide, and these were converted into the trifluoroacetamido derivatives which, on (p-nitrobenzoyl)ation and acetolysis, afforded 1-O-acetyl-2,3,6-trideoxy-5-O-(p-nitrobenzoyl)-3-(trifluoroacetamido)-d-ribo-hexofuranose. To prepare the corresponding daunosamine derivative, 2,3,6-trideoxy-3-(trifluoroacetamido)-l-lyxo-hexopyranose was converted into the diethyl dithioacetal, and this was cyclized in the same way, to afford methyl 2,3,6-trideoxy-3-(trifluoroacetamido)-α- and -β-l-lyxo-hexofuranoside. On (p-nitrobenzoyl)ation and acetolysis, both afforded 1-O-acetyl-2,3,6-trideoxy-5-O-(p-nitrobenzoyl)-3-(trifluoroacetamido)-l-lyxo-hexofuranose.     

Synthesis of 5-deoxy-d-xylo-hexose and 5-deoxy-l-arabino-hexose,and their conversion into adenine nucleosides

Anti-Markovnikov hydration of the olefinic bond of 5,6-dideoxy-1,2-O-isopropylidene-3-O-p-tolylsulfonyl-α- d-xylo-hex-5-enofuranose (4) and methyl 5,6-dideoxy-2,3-di-O-p-tolylsulfonyl-α-l-arabino-hex-5-enofuranoside (11) by the addition of iodine trifluoroacetate, followed by hydrogenation in the presence of a Raney nickel catalyst in ethanol containing triethylamine, afforded 5-deoxy-1,2-O-ísopropylidene-3-O-p-tolylsulfonyl-α-d-xylo-hexofuranose (6) and methyl 5-deoxy-2,3-di-O-p-tolylsulfonyl-α-d-arabino-hexofuranoside (14), respectively. 5-deoxy-d-xylo-hexose and 5-deoxy-l-arabino-hexose were prepared from 6 and 14, respectively, by photolytic O-detosylation and acid hydrolysis. Syntheses of 9-(5-deoxy-β-d-xylo-hexofuranosyl)-adenine and 9-(5-deoxy-α-l-arabino-hexofuranosyl)adenine are also described. Application of the sodium naphthalene procedure, for O-detosylation, to 11 is reported in connection with an alternative synthetic route to methyl 5-deoxy-α-l-arabino- hexofuranoside.     

5-thio-l-rhamnose

Two routes for the synthesis of methyl 5-S-acetyl-6-deoxy-2,3-O-isopropylidene-5-thio-l-mannofuranoside (8) have been examined. Reaction of l-rhamnose with methanol in the presence of the cation-exchange resin gives methyl 6-deoxy-α-l-mannofuranoside (2), which on conventional acetonation yields methyl 6-deoxy-2,3-O- isopropylidene-α-l-mannofuranosides (3). Compounds 3 is also obtained by acetonation of l-rhamnose followed by treatment with a mixture of methanol, acetonation, Amberlite IR-120(H⁺) resin. Chlorination of 3 with triphenylphosphine-carbon tetrachloride gives methyl 5-chloro-5,6-dideoxy-2,3-O-isopropylidene-β-d-gulofuranoside (7), which reacts with potassium thioacetate to give 8. Alternatively, 3 is iodized with ruthenium tetraoxide to methyl 6-deoxy-2,3-O-isopropylidene-α-l-lyxo-hexofuranosid-5-ulose (9), which reduced by sodium borohydride mainly to methyl 6-deoxy-2,3-O-isopropylidene-β-d-gulofuranoside (10). The O-tosyl derivative of 10 reacts with potassium thioacetate to produced 8. Hydrolysis of 8 with 90% aqueous triflouroacetic acid, followed by acetolysis with a solution of acetic acid, acetic anhydride, and sulfuric acids gives an anomeric mixture of 1,2,3,4,-tetra-O-acetyl-6-deoxy-5-thio-l-mannopyranoses (12), together with a small proportion of 1,2,3,-tri-O-acetyl-5-S-acetyl-6-deoxy-5-thio-β-l-mannofuranose (13). Deacetylation of 12 or 13 gives 5-thio-l-rhamnose (6), from which crystalline 1,2,3,4-tetra-O-(p-nitrobenzoyl)-5-thio-β-l-rhamnopyranose (14) is obtained.     

The behavior of some aldoses with 2,2-dimethoxypropane-N,N-dimethylformamide-p-toluenesulfonic acid. II. At 80 degrees

Four aldohexoses were individually subjected to the reagent mixture and temperature cited in the title; in each case, the 2,2-dimethoxypropane was present in only a small molar excess and the p-toluenesulfonic acid was used in trace amounts. D-Mannose (1) afforded the known 2,3:5,6-di-O-isopropylidene-D-mannofuranose (2) in significantly higher yield than when the reaction was conducted at room temperature. The other three aldoses, however, gave products markedly different from those formed under the milder conditions. 2-Acetamido-2-deoxy-D-mannose (3) gave a mixture of products from which methyl 2-acetamido-2-deoxy-2,3-N,O-isopropylidene-5,6-O-isopropylidene-α-D-mannofuranoside (4), 2-acetamido-2-deoxy-2,3-N,O-isopropylidene-5,6-O-isopropylidene-D-mannofuranose (5a), and methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-α-D-mannofuranoside (6a) were isolated. 2-Acetamido-2-deoxy-D-galactose (11) gave compounds identified as methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β-D-galactofuranoside (12a) and methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-galactopyranoside (13a). 2-Acetamido-2-deoxy-D-glucose (16) afforded methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β-D-glucofuranoside (17a) and methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside (18a). Evidence in support of the structures assigned to these new derivatives is presented.     

Nucleophilic displacements of methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-α-d-lyxo- and -β-l-ribo-pyranosides,and deamination of the corresponding 4-amino sugars

Reinvestigation of the reaction of methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-α-d-lyxopyranoside (4) with azide ion has shown that methyl 4-deoxy-2,3-O-isopropylidene-β-l-erythro-pent-4-enopyranoside (8, ～51.5%) is formed, as well as the azido sugar 7 (～48.5%) of an S_N2 displacement. The unsaturated sugar 8 was more conveniently prepared by heating the sulphonate 4 with 1,5-diazabicyclo-[5.4.0]undec-5-ene. An azide displacement on methyl 2,3-O-isopropylidene-4-O-toluene-p-sulphonyl-β-l-ribopyranoside (12) furnished methyl 4-azido-4-deoxy-2,3-O-isopropylidene-α-d-lyxopyranoside (13, ～66%) and the unsaturated sugar 14 (～28.5%), which was also prepared by heating the sulphonate with 1,5-diazabicyclo[5.4.0]undec-5-ene. Deamination of methyl 4-amino-4-deoxy-2,3-O-isopropylidene-α-d-lyxopyranoside (5), prepared by reduction of 13, with sodium nitrite in 90% acetic acid at ～0°, yielded methyl 2,3-O-isopropylidene-α-d-lyxopyranoside (10a, 26.2%), methyl 2,3-O-isopropylidene-β-l-ribofuranoside (21a, 18.4%), and the corresponding acetates 10b (34.5%) and 21b (21.3%). These products are considered to arise by solvolysis of the bicyclic oxonium ion 29, formed as a consequence of participation by the ring-oxygen atom in the deamination reaction. Similar deamination of methyl 4-amino-4-deoxy-2,3-O-isopropylidene-β-l-ribopyranoside (6) afforded, exclusively, the products 10a (34.4%) and 10b (65.6%) of inverted configuration. Deamination of methyl 5-amino-5-deoxy-2,3-O-isopropylidene-β-d-ribofuranoside (20) gave 22ab, but no other products. An alternative synthesis of the amino sugars 5 and 6 is available by conversion of 10a into methyl 2,3-O-isopropylidene-β-l-erythro-pentopyranosid-4-ulose (11), followed by reduction of the derived oxime 15 with lithium aluminium hydride.     

Sugars containing a carbon-phosphorus bond : Part V. 5-deoxy-5-(ethylphosphinyl)-D-ribopyranose

The Michaelis-Arbuzov reaction of methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-β-D-ribofuranoside (4) with diethyl ethylphosphonite gave methyl 5-deoxy-5-(ethoxyethylphosphinyl)-2,3-O-isopropylidene-β-D-ribofuranoside (5) which, on treatment with sodium dihydrobis(2-methoxyethoxy)aluminate, afforded methyl-5-deoxy-5-(ethylphosphinyl)-2,3-O-isopropylidene-β-D-ribofuranoside (9). Hydrolysis of 9 with hydrochloric acid yielded a mixture of the anomeric 5-deoxy-5-(ethylphosphinyl)-D-ribopyranoses (10). The hygroscopic, syrupy mixture 10 was converted into a syrup consisting of the two 1,2,3,4-tetra-O-acetyl-5-deoxy-5-(ethylphosphinyl)-D-ribopyranoses (11).     

Two crystalline pentofuranosyl bromides: tri-O-(p-nitrobenzoyl)-β-D-ribofuranosyl bromide and tri-O-(p-nitrobenzoyl)-α,β-D-xylofuranosyl bromide

Methyl α,β-D-ribofuranoside was p-nitrobenzoylated to give methyl tri-O-(p-nitrobenzoyl)-β-D-ribofuranoside (2),and this was treated with HBr in acetic acid to give tri- O-(p-nitrobenzoyl)-β-D-ribofuranosyl bromide (3). Bromide 3 could be converted into 2,5-anhydro-3,4,6-tri-O-(p-nitrobenzoyl)-D-allononitrile (4) with Hg(CN)₂, or hydrolyzed to 2,3,5-tri-O-(p-nitrobenzoyl)-D-ribose (5). On p-nitro- benzoylation, 5 gave tetra-O-(p-nitrobenzoyl)-β-D-ribofuranose (6). The synthesis of tri-O-(p-nitrobenzoyl)-α-β-D-xylofuranosyl bromide (11) started with methyl 3,5-O-isopropylidene-β-D-xyldfuranoside (7), which was p-nitrobenzoylated to give ester 8; this was then hydrolyzed, and the product p-nitrobenzoylated to give methyl tri-O-(p-nitrobenzoyl)-β-D-xylofuranoside (10) which, on treatment with HBr in CH₂Cl₂, afforded the desired bromide (11). Nucleophilic replacement with Hg(CN)₂ afforded 2,5-anhydro-3,4,6-tri-O-(p-nitrobenzoyl)-D-gulononitrile (12).     

Synthesis of D-ristosamine and its derivatives

A convenient preparative route involving eleven steps starting from D-glucose is described for the synthesis of D-ristosamine (15) hydrochloride. Methyl 2-deoxy-β-D-arabino-hexopyranoside, prepared from 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex- 1-enitol, was benzylidenated, and the product mesylated to give methyl 4,6-O-benzylidene-2-deoxy-3-O-methylsulfonyl-β-D-arabino-hexopyranoside. Azidolysis of this compound and subsequent opening of the 1,3-dioxane ring with N-bromosuccinimide gave methyl 3-azido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-βD-ribo-hexopyranoside. Simultaneous reduction of the azido and bromo groups gave a mixture that was benzoylated to give methyl N,O-dibenzoyl-β-D-ristosaminide and then hydrolyzed to 15 hydrochloride (3-amino-2,3,6-trideoxy-D-ribo-hexopyranose hydrochloride).     

Preparation of some acylated D-arabino-hexopyranosuloses and 4-deoxy-D-glycero-hex-3-enopyranosuloses

Oxidation of 1,3,4,6-tetra-O-benzoyl-α- and β-D-glucopyranose gave the tetra-O-benzoyl-α- and -β-D-arabino-hexopyranosuloses (3α and β), from which benzoic acid was readily eliminated to give the anomeric tri-O-benzoyl-4-deoxy-D-glycero-hex-3-enopyranosuloses (4α and β). The anomeric 1-O-acetyl-tri-O-benzoyl-D-arabino-hexopyranosuloses (7α and β) were obtained as very unstable syrups which readily lost benzoic acid. Treatment of tetra-O-benzoyl-2-O-benzyl-D-glucopyranose (1) with hydrogen bromide gave 3,4,6-tri-O-benzoyl-α-D-glucopyranosyl bromide (5) in one step.     

The preparation of 6-deoxy-3-O-methyl-6-nitro-D-altrose

The title compound(9) a new nitro sugar and potential starting-point for the synthesis of hitherto unknown stereoisomers in the deoxynitroinositol series, was prepared by a sequence of high-yielding reactions. Methyl 2.3-anhydro-4.6-O- benzylidene-α-D-mannopyranoside was converted into methyl 3-O-methyl-α-D-altropyranoside(3) by the action of sodium methoxide followed by debenzylidenation esssentially according to established procedures. Acetolysis of3 and subsequent Zemple´n transesterification gave syrupy 3-O-methyl-D-altrose, from which the furanoid 1,2:5.6-di-O-isopropylidene and 1,2-O-isopropylidene(7) derivatives were prepared by standard acetonation and partial Hydrolysis Periodate oxidation of 7, and addition of nitromethane to the product. furnished crystalline 6-deoxy-1.2-O-isopropylidene-3-O-methyl-6-nitro-β-D-altrofuranose(8) as the chief epimer. Deacetonation of8 by trifluoroacetic acid9 in crystalline form.     

Chemistry of glycosylamines. Isopropylidene acetals of N-acetyl-α-d-glucofuranosylamine

The reaction of N-acetyl-α-d-glucofuranosylamine with 2,2-dimethoxypropane, catalyzed by p-toluenesulfonic acid, gave 1-acetamido-2,3:5,6-di-O-isopropylidene-1-O-methyl-d-glucitol (65.6%), 1-acetamido-2,3-O-isopropylidene-1-O-methyl-d-glucitol (3.7%), and N-acetyl-5,6-O-isopropylidene-α-d-glucofuranosylamine (3.2% yield). The structures of these compounds were determined by chemical and spectroscopic methods, and their relation to the pattern of n.m.r. resonances of the isopropylidene methyl groups is discussed.     

6-thio- and -seleno-D-galactose esters of dimethylarsinous acid

The syntheses of 1,2:3,4-di-O-isopropylidene-6-S-dimethylarsino-6-thio-α-D-galactopyranose (2), methyl 6-S-dimethylarsino-6-thio-D-galactopyranoside (3), and 1,2:3,4-di-O-isopropylidene-6-Se-dimethylarsino-6-seleno-α-D-galactopyranose (8) are reported. The attempted preparation of 6-Se-dimethylarsino-6-seleno-D-galactopyranose (9) is also discussed. The n.m.r. spectra of these compounds are unexceptional, except for the slight downfield shift of the arsenic methyl resonances for the selenium compound as compared to the sulfur compound, confirming previous observations. The mass spectra of these compounds showed molecular ions for 2, 3, and 8. The u.v. spectra of the X-As (X = S, Se) chromophore are discussed in terms of a simplified MO model. 1,2:3,4-Di-O-isopropylidene-6-S-dimethylarsino-6-thio-α-D-galactopyranose (2) showed carcinostatic activity in the P388 system (mouse lymphocytic leukemia).     

Dérivés d'acides 3-(β-d-érythrofuranosyl)-pyrazolecarboxyliques

Treatment of 2,5-anhydro-1-bromo-1-deoxy-2,3-O-isopropylidene-1-p-nitrophenylhydrazono-d-ribose with methyl acetylenecarboxylate gave methyl 3-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-1-p-nitrophenylpyrazole- (8) and 5-carboxylate (9). Amidification at C-5 of 8 was easier than at C-4 of 9. Similarly, dimethyl 3-(2,3-O-isopropylidene-β-d-erythrofuranosyl)- 1 - p-nitrophenylpyrazole-4,5-dicarboxylate gave specifically a 5-carbamoyl derivative, the structure of which was established by comparison of the ¹³C-n.m.r.spectrum with those of a series of glycosylpyrazoles. The correlation between the experimental values of the chemical shifts of the carbon atoms of the pyrazole ring and the values calculated by addition of the contributions of the various groups linked to the ring was better (R 0.98) than the correlations obtained by calculation by the CNDO/2 method of the total electron population (R 0.92) or of the π-electron population of each carbon atom (R 0.85).     

O-Benzylated thio sugars. Derivatives of 2,3,6-tri-O-benzyl-1-thio-d-galactopyranose suitable for use in oligosaccharide synthesis

The 4-O-benzoyl (15a) 4-O-p-nitrobenzoyl (15b) derivatives of 2,3, 6-tri-O-benzyl-1-thio-d-galactopyranose were synthesized from allyl 2,6-di-O-benzyl-α-d-galactopyranoside (1). In the first stage of the synthesis the 3-position of 1 was benzylated by an indirect route, and also by the direct reaction (preferred) of benzyl bromide with the 3,4-O-dibutylstannylene intermediate 7. The product 6 was sequentially isomerized (allyl → 1-propenyl), acylated at the 4-position, and hydrolyzed. The free sultars 11a and 11b were converted into the thio sugars by a standard sequence involving formation of the glycosyl halides 13a and 13b and the reaction of these with appropriate sulfur nucleophiles. A third derivative (29) of 2,3,6-tri-O-benzyl-1-thio-d-galactopyranose, having a 4-O-allyl protecting group, was similarly made from the corresponding normal sugar 25. The key intermediate 22, precursor to 25, was prepared by two routes from methyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside (17).     

Syntheses of 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-d-glucopyranose (n-acetylmaltosamine) and 2-acetamido-2-deoxy-4-O-β-d-glucopyranosyl-α-d-glucopyranose

Condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-benzyl-1-O-(N-methyl)acetimidoyl-β-D-glucopyranose gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-α-D-glucopyranoside which was catalytically hydrogenolysed to crystalline 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-D-glucopyranose (N-acetylmaltosamine). In an alternative route, the aforementioned imidate was condensed with 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose, and the resulting disaccharide was catalytically hydrogenolysed, acetylated, and acetolysed to give 2-acetamido-1,3,6-tri-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-α-D-glucopyranose Deacetylation gave N-acetylmaltosamine. The synthesis of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose involved condensation of benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide in the presence of mercuric bromide, followed by deacetylation and catalytic hydrogenolysis of the condensation product.     

Glycosidation at C-4 of 2-acetamido-2-deoxy-D-glucopyranose derivatives by koenigs-knorr type condensations

The condensation of 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl bromide and 2,3,4,6-tetra-O-benzyl-D-mannopyranosyl chloride with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-α-D-glucopyranoside (1), under Koenigs-Knorr conditions, gave the fully benzylated derivatives of benzyl 2-acetamido-2-deoxy-4-O-α-D-glucopyranosyl-α-D-glucopyranoside, benzyl 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranoside, and benzyl 2-acetamido-2-deoxy-4-O-α-D-mannopyranosyl-α-D-glucopyranoside. Three further compounds, namely, benzyl 2-acetamido-3-O-benzyl-2-deoxy-6-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranosyl)-α-D-glucopyranoside, benzyl 2-acetamido-3-O-benzyl-2-deoxy-6-O-(2,3,4,6-tetra-O-benzyl-D)-mannopyranosyl)-α-D-glucopyranoside, and benzyl 2-acetamido-3-O-benzyl-2-deoxy-4,6-di-O-(2,3,4,6-tetra-O-benzyl-D-mannopyranosyl)-α-D-glucopyranoside, were formed by reaction of the respective glycosyl halide with benzyl 2-acetamido-3-O-benzyl-2-deoxy-α-D-glucopyranoside present as contaminant in 1.     

Stereoselective entry into the d-GalNAc series starting from the d-Gal one: a new access to N-acetyl-d-galactosamine and derivatives thereof

A new stereoselective preparation of N-aceyl-d-galactosamine (1b) starting from the known p-methoxyphenyl 3,4-O-isopropylidene-6-O-(1-methoxy-1-methylethyl)-β-d-galactopyranoside (10) is described using a simple strategy based on (a) epimerization at C-2 of 10 via oxidation-reduction to give the talo derivative 11, (b) amination with configurational inversion at C-2 of 11 via a S_N2-type reaction on its 2-imidazylate, (c) anomeric deprotection of the p-methoxyphenyl β-d-galactosamine glycoside 14, (d) complete deprotection. Applying the same protocol to 2,3:5,6:3′,4′-tri-O-isopropylidene-6′-O-(1-methoxy-1-methylethyl)-lactose dimethyl acetal (4), directly obtained through acetonation of lactose, the disaccharide β-d-GalNAcp-(1→4)-d-Glcp (1a) was obtained with complete stereoselectivity in good (40%) overall yield from lactose.     

Synthesis of 4-O-β-D-mannopyranosyl-L-rhamnopyranose

The title disaccharide (16) has been synthesized in 50% overall yield by way of condensation of 4,6-di-O-acetyl-2,3-O-carbonyl-α-D-mannopyranosyl bromide 5 with methyl 2,3-O-isopropylidene-α-L-rhamnopyranoside (1) in chloroform solution, in the presence of silver oxide. The disaccharide was characterized as the crystalline isopropyl alcoholate of methyl 4-O-β-D-mannopyranosyl-α-L-rhamnopyranoside (11) and as 1,2,3-tri-O acetyl-4-O- (2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl)-α-L-rhamnopyranose (15). Methyl β-D-mannopyranoside isopropyl alcoholate 7 was readily obtained in 85% yield via the reaction of bromide 5 with methanol.Reduction of 2,3-di-O-methyl-L-rhamnose with sodium borohydride, followed by acetylation, may result in the formation of an appreciable proportion of a boric ester, namely 1,5-di-O-acetyl-4-deoxy-2,3-di-O-methyl-L-rhamnitol-4-yl dimethyl borate, depending on the procedure used.