Synthesis of 2-acetamido-2-deoxy-5-thio-d-glucopyranose

2-Acetamido-2-deoxy-5-thio-d-glucopyranose (12) has been synthesized from methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside (1). Benzoylation of 1, followed by O-deisopropylidenation, gave methyl 2-acetamido-3-O-benzoyl-2-deoxy-β-d-glucofuranoside, which was converted, via selective benzoylation and mesylation, into methyl 2-acetamido-3,6-di-O-benzoyl-2-deoxy-5-O-mesyl-β-d-glucofuranoside (5). Treatment of 6, formed by the action of sodium methoxide in chloroform on 5, with thiourea gave methyl 2-acetamido-2,5,6-trideoxy-5,6-epithio-β-d-glucofuranoside (7), which was converted into the 5-thio compound 9 by cleavage of the epithio ring in 7 with potassium acetate. Alkaline treatment of 10, derived from 9 by hydrolysis, afforded the title compound. Evidence in support of the structures assigned to the new derivatives is presented.     

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 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-D-mannose,and its interaction with D-mannose-specific lectins

Condensation of 3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal with 2-methyl-(3,4,6-tri-O-acetyl- 1,2-dideoxy-α-D-glucopyrano)-[2′, 1′:4,5]-2-oxazoline in the presence of a catalytic amount of p-toluenesulfonic acid afforded crystalline 2-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal (3) in 25% yield. Catalytic deacetylation of 3 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave 2-O-(2-acetamido-2-deoxy-α-D-glucopyranosyl)-D-mannose (4). Treatment of 3 with boiling 0.5% methanolic hydrogen chloride under reflux gave methyl 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannopyranoside (5) and methyl 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannofuranoside (6). The inhibitory activities of 4, 5, and 6 against the hemagglutinating and mitogenic activities of Lens culinaris and Pisum sativum lectins and concanavalin A were assayed. From the results of these hapten inhibition studies, subtle differences of specificity between these D-mannose-specific lectins were confirmed.     

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 N-[2-O-(2-acetamido-2,3-dideoxy-5-thio-d-glucopyranose-3-yl)-d-lactoyl]-l-alanyl-d-isoglutamine

N-[2-O-(2-Acetamido-2,3-dideoxy-5-thio-d-glucopyranose-3-yl)-d-lactoyl]-l-alanyl-d-isoglutamine, in which the ring-oxygen atom of the sugar moiety in N-acetylmuramoyl-l-alanyl-d-isoglutamine (MDP) has been replaced by sulfur, was synthesized from 2-acetamido-2-deoxy-5-thio-α-d-glucopyranose (1). O-Deacetylation of the acetylated acetal, derived from the methyl α-glycoside of 1 by 4,6-O-isopropylidenation and subsequent acetylation, gave methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-5-thio-α-d-glucopyranoside (4). Condensation of 4 with l-2-chloropropanoic acid, and subsequent esterification, afforded the corresponding ester, which was converted, viaO-deisopropylidenation, acetylation, and acetolysis, into 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-5-thio-α-d-glucopyranose (12). Coupling of the acid, formed from 12 by hydrolysis, with the methyl ester of l-alanyl-d-isoglutamine, and de-esterification, yielded the title compound.     

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.     

Synthèse du méthyl-2-acétamido-2-désoxy-β-D-glucofuranoside et de dérivés

Methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β-D-glucofuranoside was prepared in excellent yield from methyl 2-benzamido-2-deoxy-5,6-O-isopropylidene-β-D-glucofuranoside by alkaline hydrolysis, followed by selective N-acetylation. Treatment with 60% acetic acid at room temperature gave syrupy methyl 2-acetamido-2-deoxy-β-D-glucofuranoside, characterized by a crystalline tri-O-p-nitrobenzoyl derivative. The same treatment, at 100° gave methyl 2-acetamido-2-deoxy-β-D-glucopyranoside. In an alternative procedure, the selective N-acetylation was performed after acetic acid hydrolysis of methyl 2-amino-2-deoxy-5,6-O-isopropylidene-β-D-glucofuranoside. Several derivatives of methyl 2-acetamido-2-deoxy-β-D-glucofuranoside were prepared and compared with the corresponding pyranosides. The furanoside structure was clearly demonstrated by mass spectrometry and periodate oxidation.     

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).     

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.     

Synthesis of 1-deoxy-3-C-methyl-d-fructose and 1-deoxy-3-C-methyl-d-sorbose

Hydroxylation of trans-1,3,4-trideoxy-5,6-O-isopropylidene-3-C-methyl-d-glycero-hex-3-enulose with osmium tetraoxide gave a mixture of 1-deoxy-5,6-O-isopropylidene-3-C-methyl-d-arabino- and -d-xylo-hexulose that was partially resolved by acetonation to give 1-deoxy-2,3:4,5-di-O-isopropylidene-3-C-methyl-β-d-fructopyranose (4), 1-deoxy-3,4:5,6-di-O-isopropylidene-3-C-methyl-keto-d-fructose (5), and 1-deoxy-2,3:4,6-di-O-isopropylidene-3-C-methyl-α-d-sorbofuranose (6). Treatment of a mixture of 4 and 5 with sodium borohydride gave, after column chromatography, 4 and 1-deoxy-3,4:5,6-di-O-isopropylidene-3-C-methyl-d-manno- and -d-gluco-hexitol. Deuterated derivatives corresponding to 4–6 were obtained when isopropylidenation was carried out with acetone-d₆. Deacetonation of 4 and 5 yielded 1-deoxy-3-C-methyl-d-fructose, and 6 similarly afforded 1-deoxy-3-C-methyl-d-sorbose.     

Branched-chain glycosyl α-amino acids : Part II. Synthesis of 2-D- and 2-L-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)glycine. Analogs of the sugar moiety of the polyoxins

Stereospecific hydroxylation of 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-trans-and 3-C-cis-(methoxycarbonylmethylene)-α-D-ribo-hexofuranose (2 and 3, respectively), with potassium permanganate in pyridine afforded 3-C-[S- and R-hydroxy-(methoxycarbonyl)methyl]-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose, (6 and 7, respectively), in a combined yield, after chromatography, of 43%. Selective formation of monomethanesulfonates (9a and 10a) and p-toluenesulfonates (9b and 10b), followed by treatment with sodium azide and reduction of the azide, afforded the methyl 2-D-(and 2-L-)(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)-glycinates (12a and 13a, respectively). Basic hydrolysis of the latter compounds yielded 2-D- and 2-L-(3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-yl)glycine (12b and 13b, respectively). The structures of the glycosyl amino acids were correlated with that of L-alanine by circular dichroism.     

The synthesis of chlorodeoxyhexofuranoid derivatives

The reaction of 1,2-O-isopropylidene-α- d-glucofuranose with sulfuryl chloride at 0° and at 50° afforded 6-chloro-6-deoxy-1,2-O-isopropylidene-α- d-glucofuranose 3,5-bis(chlorosulfate) ( 3) and 5,6-dichloro-5,6-dideoxy-1,2-O-isopropylidene-β- l-idofuranose 3-chlorosulfate ( 7, not characterised), respectively. Dechlorosulfation of 3 afforded the hydroxy derivative, whereas treatment of 3 with pyridine gave the 3,5-(cyclic sulfate). Dechlorosulfation of 7 afforded 5,6-dichloro-5,6-dideoxy-1,2-O-isopropylidene-β- l-idofuranose which, on acid hydrolysis, was converted into 3,6-anhydro-5-chloro-5-deoxy- l-idofuranose. 5-Chloro-5-deoxy-α- l-idofuranosidurono-6,3-lactone and 5-chloro-5-deoxy-β- l-idofuranurono-6,3-lactone derivatives were also prepared.     

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.     

Synthesis of 2-acetamido-2-deoxy-3-O-β-d-mannopyranosyl-d-glucose

Condensation of 4,6-di-O-acetyl-2,3-O-carbonyl-α-d-mannopyranosyl bromide with benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-d-glucopyranoside (2) gave an α-d-linked disaccharide, further transformed by removal of the carbonyl and benzylidene groups and acetylation into the previously reported benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-α-d-mannopyranosyl)-α-d-glucopyranoside. Condensation of 3,4,6-tri-O-benzyl-1,2-O-(1-ethoxyethylidene)-α-d-glucopyranose or 2-O-acetyl-3,4,6-tri-O-benzyl-α-d-glucopyranosyl bromide with 2 gave benzyl 2-acetamido-3-O-(2-O-acetyl-3,4,6-tri-O-benzyl-β-d-glucopyranosyl)-4,6-O-benzylidene-2-deoxy-α-d-glucopyranoside. Removal of the acetyl group at O-2, followed by oxidation with acetic anhydride-dimethyl sulfoxide, gave the β-d-arabino-hexosid-2-ulose 14. Reduction with sodium borohydride, and removal of the protective groups, gave 2-acetamido-2-deoxy-3-O-β-d-mannopyranosyl-d-glucose, which was characterized as the heptaacetate. The anomeric configuration of the glycosidic linkage was ascertained by comparison with the α-d-linked analog.     

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.     

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.     

Glycosyl α-amino acids : Part III. Synthesis of D- and L-2-(1,2:5,6-DI-O-isopropylidene-α-D-galactofuranos-3-YL)glycine

Stereospecific hydroxylation of (E)-3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-(methoxycarbonylmethylene)-α-D-xylo-hexofuranose (2) with potassium permanganate in pyridine afforded pure 3-C-[(R)-hydroxy(methoxycarbonyl)methyl]-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose (5) in 55% yield. Mesylation of the diol 5 in pyridine yielded the monomethanesulfonate 6 and, in addition, a small proportion of an unsaturated, exocyclic sulfonate 7. Treatment of 6 with sodium azide in N-N-dimethylformamide and reduction of the resultant α-azido ester 9 afforded methyl D- (and L-) 2-(1,2:5,6-di-O-isopropylidene-α-D-galactofuranos-3-yl)glycinate, (11a) and (10a), respectively. Basic hydrolysis of 11a and 10a yielded D- and L-2-(1,2:5,6-di-O-isopropylidene-α-D-galactofuranos-3-yl)glycine (11b) and (10b), respectively. The structures of the glycosyl α-amino acids were correlated with that of L-alanine by circular dichroism.     

Synthesis of phenyl O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-α-d-galactopyranoside

phenyl 2-acetamido-2-deoxy-4,6-O-(p-methoxybenzylidene)-3-O-[4,6-O-(p-methoxybenzylidene)-β-d-alactopyranosyl]-α-d-galactopyranoside (3) was prepared from phenyl 2-acetamido-2-deoxy-4,6-O-(p-methoxybenzylidene)-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-α-d-galactopyranoside by zemplén deacetylation, followed by reaction with p-methoxybenzaldehyde in the presence of anhydrous zinc chloride. The selective benzoylation of 3 gave the 3′-benzoate which, on condensation with 2,3,4-tri-O-benzyl-α- l-fucopyranosyl bromide under catalysis by halide ion, afforded a crystalline trisaccharide from which the title trisaccharide was obtained by debenzoylation followed by catalytic hydrogenolysis.     

Biosynthesis of chondroitin sulfate. Purification of UDP-D-xylose:core protein beta-D-xylosyltransferase by affinity chromatography

Silver carbonate on Celite (the Fetizon reagent) was shown to be selective as an oxidizing agent, and convenient for the preparation of various aldonolactones. Whereas substituted aldoses having the 1-hydroxyl group free were readily converted into the corresponding lactones, partially protected 2-acetamido-2-deoxypyranoses having more than one free hydroxyl group were selectively oxidized at C-1. The oxidation was carrried out in boiling benzene or 1,4-dioxane. A series of partially protected 2-acetamido-2-deoxy-1,5-aldonolactones [2-acetamido-4,6-O-benzylidene-2-deoxy-D-mannono-1,5-lactone (13),2-acetamido-4,6-O-benzylidene-2-deoxy-D-glucono-1,5-lactone (15), 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-glucono-1,5-lactone (18), 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-mannono-1,5-lactone (20), 2-acetamido-2-deoxy-3,4-di-O-methyl-D-mannono-1,5-lactone (24), and 2-acetamido-2-deoxy-3,4-di-O-methyl-D-glucono-1,5-lactone (25)] was thus prepared; for these, the oxidation was accompanied by two side-reactions: (a) an elimination (dehydration) that gave the unsaturated lactones [2-acetamido-4,6-O-benzylidene-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (12), 2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-D-erythro-hex-2-enono-1,5-lactone (17), and 2-acetamido-2,3-dideoxy-4-O-methyl-D-erythro-hex-2-enono-1,5-lactone (23)], and (b) partial gluco-to-manno epimerization occurring during the oxidation of 2-acetamido-4,6-O-benzylidene-2-deoxy-D-glucopyranose (14), 2-acetamido-2-deoxy-4,6-O-isopropylidene-D-glucopyranose (16), and 2-acetamido-2-deoxy-3,4-di-O-methyl-D-glucopyranose (22).The free unsaturated lactone, 2-acetamido-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (26), was obtained on hydrolysis of the isopropylidene group in lactone 17.     

Synthesis of 3-amino-2,3,6-trideoxy-ll-lyxo-hexose (daunosamine) hydrochloride from d-glucose

Three different approaches starting from 1,2-O-isopropylidene-α-d-glucofuranose were tested for the synthesis of daunosamine hydrochloride (24), the sugar constituent of the antitumor antibiotics daunomycin and adriamycin. The third route, affording 24 in ~5% overall yield in 11 steps, constitutes a useful, preparative synthesis, 3,5,6-Tri-O-benzoyl-1,2-O-isopropylidene-α-d-glucofuranose was converted via methyl 2,3-anhydro-β-d-mannofuranoside into methyl 2,3:5,6-dianhydro-α-l-gulofuranoside, the terminal oxirane ring of which was split selectively on reduction with borohydride, to afford methyl 2,3-anhydro-6-deoxy-α-l-gulofuranoside (31). Compound 31 was converted into methyl 2,3-anhydro-5-O-benzyl-6-deoxy-α-l-gulofuranoside, which was selectively reduced at C-2 on treatment with lithium aluminum hydride, affording methyl 5-O-benzyl-2,6-dideoxy-α-l-xylo-hexofuranoside. Subsequent mesylation, and replacement of the mesoloxy group by azide, with inversion, afforded methyl 3-azido-5-O-benzyl-2,6-dideoxy-α-l-lyxo-hexofuranoside, which could be converted into either 24 or methyl 3-acetamido-5-O-acetyl-2,3,6-trideoxy-α-l-lyxo-hexofuranoside, which can be used as a starting material for the synthesis of daunomycin analogs.