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 2,5-dideoxy-2-C-methyl-d-arabinose derivatives from methyl 2,3-anhydro-5-deoxy-α-d-ribofuranoside

Treatment of methyl 2,3-anhydro-5-deoxy-α-d-ribofuranoside with lithium dimethyl cuprate gave methyl 2,5-dideoxy-2-C-methyl-α-d-arabinofuranoside (54% yield) and methyl 3,5-dideoxy-3-C-methyl-α-d-xylofuranoside (10%). The former was converted into its 3-O-acetyl and 3-O-benzyl derivatives, which, upon acid hydrolysis, afforded 3-O-acetyl- and 3-O-benzyl-2,5-dideoxy-2-C-methyl-d-arabinofuranose in 60–75% overall yield. Treatment of the 3-O-benzyl compound with ethanethiol in the presence of trifluoromethanesulfonic acid afforded 3-O-benzyl-2,5-dideoxy-2-C-methyl-d-arabinose diethyl dithioacetal (20%) and ethyl 3-O-benzyl-2,5-dideoxy-2-C-methyl-1-thio-α-d-arabinoside (73%). The former, which was also available from the latter by equilibration in acidic ethanethiol, was acetylated at O-4 and the product converted into the corresponding dimethyl acetal (85% overall yield). This compound was, after debenzylation, hydrolyzed with acid, to provide 4-O-acetyl-2,5-dideoxy-2-C-methyl-d-arabinose in 70% overall yield.     

Some metabolites of Botrytis cinerea related to botcinolide

Four new botcinolide derivatives 4-O-methylbotcinolide, 3-O-acetyl-5-O-methylbotcinolide, 3-O-acetyl-2-epibotcinolide and 2-epibotcinolide have been isolated from the plant pathogen, Botrytis cinerea. Their structures have been established by extensive spectroscopic methods.     

Intramolecular cyclization of pentose and hexose dithioacetals

The intramolecular cyclization of O-tosyl derivatives of dithioacetals of d-ribose, d-arabinose, and d-glucose was investigated. p-Toluenesulfonylation of d-glucose diethyl dithioacetal gave 3,6-anhydro-d-glucose diethyl dithioacetal. Variously substituted 5-O-tosyl-d-glucose dibenzyl dithioacetals gave derivatives of either 2,5-anhydro-l-idose dibenzyl dithioacetal, benzyl 1,5-dithio-l-idopyranoside, or l-idose dibenzyl dithioacetal. Likewise, 4-O-tosyl-d-glucose dibenzyl dithioacetal derivatives gave benzyl 1,4-dithio-d-galactofuranoside derivatives.     

Photo-oxygenation of glycosylfurans. Rearrangement of C-glycosyl into O-glycosyl derivatives

Photo-oxygenation of 3-ethoxycarbonyl-5-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-2-methylfuran and 3-hydroxymethyl-5-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-2-methylfuran yields the corresponding endo-peroxides which rearrange at room temperature into the O-glycosyl derivatives ethyl 2,3-O-isopropylidene-β-d-erythrofuranosyl 2-acetylfumarate and 2,3-O-isopropylidene-β-d-erythrofuranosyl 3-acetyl-3-hydroxymethylacrylate, respectively. The endo-peroxides can be reduced without rearrangement, yielding C-glycosyl derivatives. Alcoholysis of the O-glycosyl derivatives yields 2,3-O-isopropylidene-d-erythrose, dialkyl 2-acetyl-3-alkoxysuccinates, 4-ethoxycarbonyl-5-methoxy-5-methyl-2-oxo-2,5-dihydrofuran and 4-hydroxymethyl-5-methoxy-5-methyl-2-oxo-2,5-dihydrofuran.     

Synthèse des méthyl-2,4,6-tridésoxy-4-trifluoroacétamido-l-hexopyranosides. Accès à de nouvelles anthracyclines

The four diastereoisomeric methyl 2,4,6-trideoxy-4-trifluoroacetamido-l-hexopyranosides have been synthesized. Coupling of the corresponding 1-O-acetyl-3-O-benzoyl-l-lyxo and 1-O-acetyl-3-O-p-nitrobenzoyl-l-arabino derivatives with daunomycinone in the presence of p-toluensulfonic acid as catalyst afforded two new anthracyclines.     

The synthesis of O-methyl derivatives of 4-thiopentofuranosides and 2,5-anhydropentoses

Heating of 2,3,5-tri-O-methyl-4-O-p-tolylsulfonyl-D-ribose diethyl dithioacetal and dibenzyl dithioacetal in aqueous pyridine gave 4-S-ethyl-2,3,5-tri-O-methyl-4-thio-l-lyxose and benzyl 2,3,5-tri-O-methyl-α-1,4-dithio-l-lyxofuranoside, respectively. Similar rearrangements to the 4-thiofuranoside were observed with 2,3,5-tri-O-methyl-4-O-p-tolylsulfonyl-D-xylose and -D-lyxose dibenzyl dithioacetals. 2,3,4-Tri-O-methyl- 5-O-p-tolylsulfonyl-D-ribose or -D-xylose dibenzyl dithioacetal, however, gave upon heating with sodium iodide in acetone 2,5-anhydro-3,4-di-O-methyl-D-ribose or -D-xylose dibenzyl dithioacetal, respectively.     

Studies on dextranases. 3. Insolubilization of a bacterial dextranase

Ammonium hydroxide treatment of 1,6:2,3-dianhydro-4-O-benzyl-β-D-mannopyranose, followed by acetylation, gave 2-acetamido-3-O-acetyl-1,6-anhydro-4-O-benzyl-2-deoxy-β-D-glucopyranose which was catalytically reduced to give 2-acetamido-3-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose (6), the starting material for the synthesis of (1→4)-linked disaccharides bearing a 2-acetamido-2-deoxy-D-glucopyranose reducing residue. Selective benzylation of 2-acetamido-1,6-anhydro-2-deoxy-β-D-glucopyranose gave a mixture of the 3,4-di-O-benzyl derivative and the two mono-O-benzyl derivatives, the 4-O-benzyl being preponderant. The latter derivative was acetylated, to give a compound identical with that just described. For the purpose of comparison, 2-acetamido-4-O-acetyl-1,6-anhydro-2-deoxy-β-D-glucopyranose has been prepared by selective acetylation of 2-acetamido-1,6-anhydro-2-deoxy-β-D-glucopyranose.Condensation between 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide and 6 gave, after acetolysis of the anhydro ring, the peracetylated derivative (17) of 2-acetamido-2-deoxy-4-O-β-D-glucopyranosyl-α-D-glucopyranose. A condensation of 6 with 3,4,6-tri-O-acetyl-2-deoxy-2-diphenoxyphosphorylamino-α-D-glucopyranosyl bromide likewise gave, after catalytic hydrogenation, acetylation, and acetolysis, the peracylated derivative (21) of di-N-acetylchitobiose.     

Chemical modification of aminocyclitol antibiotics

The aminocyclitol antibiotic neamine has been chemically modified at the hydroxyl group on C-6 of the 2-deoxystreptamine moiety. The partially acetylated neamine derivatives, 6,3′,4′-tri-O-acetyl- (3) and 5,3′,4′-tri-O-acetyl-1,3,2′,6′-tetra-N-(ethoxycarbonyl)neamine (4), were prepared by random hydrolysis of the 5,6-O-ethoxyethylidene derivative (2), followed by chromatographic purification. Condensation of 4 and 2,3,5-tri-O-benzoyl-d-ribofuranosyl chloride led to 6-O-(β-d-ribofuranosyl)neamine (7). Analogous condensation of 4 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide or 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide afforded the corresponding 6-O-(d-hexopyranosyl)neamines.     

Dioxolane and dioxane acetal derivatives of D-allose: Condensation of 3-O-benzyl-D-allose with acetaldehyde

Condensation of 3-O-benzyl-D-allose with acetaldehyde forms a complex mixture from which potentially useful mono- and di-O-ethylidene derivatives were isolated and identified. Compounds isolated and identified after conversion of unsubstituted hydroxyl groups into the corresponding acetates included 1,2-di-O-acetyl-3-O-benzyl-4,6-O-ethylidene-β-D-allopyranose; 5,6-di-O-acetyl-3-O-benzyl-1,2-O-(R)-ethylidene-α-D-allofuranose; and two 3-O-benzyl-1,2:5,6-di-O-ethylidene-α-D-allofuranoses, both having the R configuration in the 1,2-O-ethylidene ring. Furanose and pyranose conformations were determined by n.m.r. analysis, and the location and configuration of each acetal ring was established. The benzyl ether group in the furanose derivatives was removed by catalytic hydrogenation with subsequent formation of 3-O-acetyl analogs.     

Chemical Syntheses of 4-O-α and -β-D-galactopyranosyl-D-galactose and 3-O-α- and -β-D-galactopyranosyl-D-galactose

Reaction of 2,3-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (2) with 2,3,4,6-tetra- O-acetyl-α-D-galactopyranosyl bromide in the presence of mercuric cyanide and subsequent acetolysis gave 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose (4, 40%) and 1,2,3,6-tetra-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranose (5, 30%). Similarly, reaction of 2,4-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (3) gave 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl)-α-D-galactopyranose (6, 46%) and 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-α-D-galactopyranose (7, 14%). The anomeric configurations of 4-7 were assigned by n.m.r. spectroscopy. Deacetylation of 4-7 afforded 4-O-α-D-galactopyranosyl-D-galactose (8), 4-O-β-D-galactopyranosyl-D-galactose (9), 3-O-α-D-galactopyranosyl-D-galactose (10), and 3-O-β-D-galactopyranosyl-D-galactose (11), respectively.     

The first replacement of a chlorosulphonyloxy group by chlorine at C-2 in methyl α-D-glucopyranoside and sucrose derivatives

Treatment of methyl 3-O-acetyl-4,6-O-benzylidene-α-D-glucopyranoside 2-chlorosulphate (2), 3,4,6,3′,4′,6′-hexa-O-acetylsucrose 2,1′-bis(chlorosulphate), 3,4,6,3′,4′,6′-hexa-O-acetyl-1′-O-benzoylsucrose 2-chlorosulphate, and 3,4,3′,4′-tetra-O-acetyl-6,6′-dichloro-6,6′-dideoxysucrose 2,1′-bis(chlorosulphate) with lithium chloride in hexamethylphosphoric triamide gave the corresponding chlorodeoxy-manno derivatives. Treatment of the 2-chlorosulphate 2 with such nucleophilic reagents as lithium bromide, sodium azide, sodium chloride, and sodium benzoate in hexamethylphosphoric triamide gave the 2-hydroxy compound as a major product. Selective chlorination at C-1′ was achieved when 3,4,6,3′,4′,6′-hexa-O-acetylsucrose was treated with sulphuryl chloride in a mixture of pyridine and chloroform.     

Accès à des sulfures d'alkyle et de furannyle à partir de dithio-acétals de pentoses

Sodium iodide—zinc in N,N-dimethylformamide at 150° converted 2,5-anhydro-3,4-di-O-p-tolylsulfonyl-D-xylose diisobutyl dithioacetal into a mixture of three substituted furans, namely 2-[(isobutylthio)methyl]furan (2), and its 3-isobutylthio- (3), and 4-isobutylthio- (5) derivatives. The relative proportions of 2, 3, and 5, determined by g.l.c.—mass spectrometry, varied according to the relative proportions of reactants employed. A similar type of transposition—elimination is also encountered in the absence of sodium iodide. Compound 3 is also produced from D-xylose disobutyl dithioacetal by extended treatment with 2-methylpropanethiol—hydrochloric acid. The furan derivatives 3 and 5 were characterized mainly by n.m.r.—spectral studies on their Diels—Alder adducts with maleic anhydride, and the mechanism of their formation is discussed. 2,5-Anhydro-3,4-di-O-p-tolylsulfonyl-D-xylose ethylene dithioacetal (13), its ribo epimer (15), and its L-arabino diisobutyl dithioacetal analog (20) all reacted with sodium iodide—zinc in N,N-dimethylformamide exclusively by an E2 type of elimination with formation of the anticipated 3-alkenes, namely 2,5-anhydro-3,4-dideoxy-D-glycero-pent-3-enose ethylene dithioacetal (14) and its diisobutyl dithioacetal analog.     

The linkage of 4-O-methyl-L-galactose in the sulphated polysaccharide of Aeodes ulvoidea

Methyl 2-acetamido-5,6-di-O-benzyl-2-deoxy-β-d-glucofuranoside (11) was obtained in six steps from the known methyl 3-O-allyl-2-benzamido-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside. Mild acid hydrolysis, followed by benzylation gave the 5,6-dibenzyl ether. The benzamido group was exchanged for an acetamido group by strong alkaline hydrolysis, followed by N-acetylation, and the allyl group was isomerized into a 1-propenyl group that was hydrolyzed with mercuric chloride. Treatment of 11 with l-α-chloropropionic acid and with diazomethabe gave methyl 2-acetamido-5,6-di-O-benzyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucofuranoside which formed on mercaptolysis the internal ester 16, further converted into 2-acetamido-4-O-acetyl-5,6-di-O-benzyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-d-glucose diethyl dithioacetal (18) by alkaline treatment followed by esterification with diazomethane and acetylation. Attempts to remove the O-acetyl group of the corresponding dimethyl acetal 20 with sodium methoxide in mild conditions were not successful.     

Acetylated allose-containing flavonoid glucosides from Stachys anisochila

In continuation of our chemosystematic study of Stachys (Labiatae) we have isolated the previously reported isoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranoside] (1) and 3′-hydroxy-4′-O-methylisoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranoside] (4) and four new allose-containing flavonoid glycosides from S. anisochila. The new glycosides are hypolaetin 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranside] (6) as well as the three corresponding diacetyl analogues of 1, 4 and 6, isoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside], 3′-hydroxy-4′-O-methylisoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside] and hypolaetin 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside]. Extensive two-dimensional NMR studies (proton-carbon correlations, COSY experiments) allowed assignment of all ¹H NMR sugar signals and a correction of the ¹³C NMR signal assignments for C-2 and C-3 of the allose.     

Photo-oxygenation of polyhydroxyalkylfurans: rearrangement of O-acetyl derivatives

The photo-oxygenation of ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-lyxo-tetritol-1-yl)-3-furoate, ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)-3-furoate, 3-acetyl-2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)furan, and ethyl 5-(1,4-di-O-acetyl-2,3-O-isopropylidene-d-lyxo-tetritol-1-yl)-2-methyl-3-furoate yielded the corresponding 1,4-endo-peroxides (3a–3d as pairs of diastereomers). Each diastereomer of the pairs 3a and 3d was isolated by fractional crystallisation. The rearrangement of the endo-peroxides at room temperature, by dissolution in CDCl₃, yielded the corresponding diepoxides and monoepoxides. The reduction of 3a–3d with methyl sulphide yielded the corresponding γ-diketones, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-lyxo-oct-2-en-4-ulosonate, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-arabino-oct-2-en-4-ulosonate, 3-C-acetyl-6,7,8,9-tetra-O-acetyl-1,3,4-trideoxy-d-arabino-non-3-eno-2,5-diulose, and ethyl (E)-2-C-acetyl-5,8-di-O-acetyl-2,3-dideoxy-6,7-O-isopropylidene-d-lyxo-oct-2-en-4-ulosonate, which can isomerise into the corresponding Z isomers.     

Silica gel-catalyzed migration of acetyl groups from a sulfur to an oxygen atom

During the chromatographic separation of 3-S-acetyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose on silica gel, a migration of the acetyl group from S to O was observed to give 6-O-acetyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose, whereas 3-S-acetyl-6-O-benzoyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose gave 5-O-acetyl-6-O-benzoyl-1,2-O-isopropylidene-3-thio-α-d-allofuranose. No acetyl migration was observed, however, in the case of 3-O-acetyl-1,2-O-isopropylidene-α-d-allofuranose.     

Synthesis and biological activity of O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses

Benzoylation of benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-α-d-glucopyranoside, benzyl 2-deoxy-2-(dl-3-hydroxytetradecanoylamino)-4,6-O-isopropylidene-α-d-glucopyranoside, and benzyl 2-deoxy-4,6-O-isopropylidene-2-octadecanoylamino-β-d-glucopyranoside, with subsequent hydrolysis of the 4,6-O-isopropylidene group, gave the corresponding 3-O-benzoyl derivatives (4, 5, and 7). Hydrogenation of benzyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-α-d-glucopyranoside, followed by chlorination, gave a product that was treated with mercuric actate to yield 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucopyranose (11). Treatment of 11 with ferric chloride afforded the oxazoline derivative, which was condensed with 4, 5, and 7 to give the (1→6)-β-linked disaccharide derivatives 13, 15, and 17. Hydrolysis of the methyl ester group in the compounds derived from 13, 15, and 17 by 4-O-acetylation gave the corresponding free acids, which were coupled with l-alanyl-d-isoglutamine benzyl ester, to yield the dipeptide derivatives 19–21 in excellent yields. Hydrolysis of 19–21, followed by hydrogenation, gave the respective O-(N-acetyl-β-muramoyl-l-alanyl-d-isoglutamine)-(1→6)-2-acylamino-2-deoxy-d-glucoses in good yields. The immunoadjuvant activity of these compounds was examined in guinea-pigs.     

18-Norspirostanol derivatives from Trillium tschonoskii

Three 18-norspironstanol oligoglycosides partly acylated in their sugar moieties were isolated from the underground parts of Trillium tschonoskii. Their structures were characterized, as 1-O-[2″,3″,4″-tri-O-acetyl-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl]-epitrillenogenin-24-O-acetate, 1-O-[2″,3″,4″-tri-O-acetyl-α-l-rhamno-pyranosyl-(1 → 2)-α-l-arabinopyranosyl]-epitrillenogenin and 1-O-[2″,4″-di-O-acetyl-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranosyl]-epitrillenogenin-24-O-acetate.     

Entwicklung eines syntheseblocks der 3-O-β-d-galactopyranosyl-d-galactopyranose

In the presence of trimethylsilyl triflate, 1,2,3,4,6-penta-O-acetyl-β-d-galactopyranose reacted with benzyl 4-O-acetyl-2,6-di-O-benzyl-β-d-galactopyranoside to give benzyl 2,6-di-O-benzyl-3-O-β-d-galactopyranosyl-β-d-galactopyranoside further converted into the synthetic block 1,2,4,6-tetra-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d-galactopyranose. This, in the presence of a Lewis acid catalyst and with the corresponding glycosyl acceptors, gave 8-methoxycarbonyloctyl 3-O-β-d-galactopyranosyl-β-d-galactopyranoside and 8-methoxycarbonyloctyl O-β-d-galactopyranosyl-(1→3)-O-β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-α-d-galactopyranoside.