Michèle Blanc-Muesser

Conformations in solution of the stereoisomeric, peracetylated aldohexose dimethyl acetals and diethyl dithioacetals

Abstract The conformations in solution of acyclic carbohydrate derivatives having four contiguous asymmetric centers in all eight diastercoisomeric forms have been studied by 1 H-n.m.r. spectroscopy. The 250-MHz, 1 H-n.m.r. spectra for solutions in chloroform- d of eight penta- O -acetylaldohexose dimethyl acetals, and the corresponding diethyl dithioacetals, furnished a complete set of chemical shifts and proton-proton spin-couplings that are interpreted in terms of conformational compositions at room temperature. The galacto and manno derivatives adopt planar, extended conformations, whereas the other six stereoisomers all adopt one or more non-extended (“sickle”) conformations. The results are interpreted on the basis of the avoidance of parallel 1,3-interactions of substituents. The conformational assignments are correlated with observations made previously for aldopentose analogs. An assessment is made of the extent to which valid conformational predictions may be advanced for four-center, and longer, asymmetrically substituted chains, based on observations made for shorter-chain analogs.

Syntheses stereoselectives de 1-thioglycosides☆☆☆

Abstract 2,3,4,6-Tetra-O-acetyl-β- d -mannopyranosyl chloride (2) was obtained in 70% yield by the action of lithium chloride on 2,3,4,6-tetra-O-acetyl-α- d -mannopyranosyl bromide (1) in hexamethylphosphoric triamide. p-Nitrobenzenethiol reacted with 1 and 2 as well as with 2,3,4,6-tetra-O-acetyl-α- d -glucopyranosyl bromide (9) or its β- d -chloro analog (10), giving exclusively and in good yield the corresponding p-nitrophenyl 1-thioglycosides of inverted anomeric configuration. The 1,2-cis- d -manno and -glucop-nitrophenylglycosides were likewise prepared. α- d -Glucopyranosyl 1-thio-α- d -glucopyranoside was similarly obtained by the action of the sodium salt of 1-thio-α- d -glucopyranose on the β-chloride 10 in hexamethylphosphoric triamide, or by treatment of 10 with sodium sulfide, with subsequent deacetylation. Analogous procedures allowed the preparation of β- d -mannopyranosyl 1-thio-β- d -mann opyranoside, the corresponding α,β anomer and α- d -glucopyranosyl 1-thio-α- d -mannopyranoside, starting from bromide 1, 1-thio-α- d -mannopyranose (8),and chloride 10, respectively. When acetone was used as solvent, the reaction between 1 and 8 led instead to the α,α anomer. The thio disaccharides that are interglycosidic 4-thio analogs of methyl 4-O-(β- d -galactopyranosyl)-α- d -galactopyranoside, methyl α-cellobioside, and methyl α-maltoside, respectively, were obtained by way of the peracetates of methyl 4-thio-α- d -galactopyranoside and -glucopyranoside by reaction of the corresponding thiolates with tetra-O-acetyl-α- d -galactopyranosyl bromide, bromide 9, or chloride 10, respectively, in hexamethylphosphoric triamide. These 1-thioglycosides, and (1→1)- and (1→4)-thiodisaccharides, were characterized by 1H- and 1 3C-n.m.r. spectroscopy. Correlations were established between the polarity of the sulfur atom and certain proton and carbon chemical-shifts in the 1-thioglycosides in comparison with the O-glycosyl analogs; these correlations permitted in particular the unambigous attribution of anomeric configuration.

Stereoselective syntheses of O- and S-nitrophenyl glycosides. Part III. Syntheses in the α-D-galactopyranose and α-maltose series

The action of p-nitrophenol on penta-O-acetyl-β-D-galactopyranose in dichloromethane, in the presence of stannic tetrachloride, gave p-nitrophenyl α-D-galactoside in fair yield. This technique failed when o-nitrophenol was used. Tetra-O-acetyl-β-D-galactopyranosyl and hepta-O-acetyl-β-maltosyl chlorides were converted to p- or o-nitrophenyl α-D-glycosides and p-nitrophenyl α-D-1-thioglycosides in good yield using hexamethylphosphoramide as a solvent and the sodium salt of the phenols as nucleophiles. The galactosides have been functionalized for further condensation at the C-4 position by selective benzoylation.

Karplus-type equation for vicinal carbon-proton coupling constants for the CSCH pathway in 1-thioglycosides

Abstract The Karplus-type relationship for 3 J CSCH values and glycosidic dihedral angles in 1-thioglycosides, based on 3 J C,H values for a series of conformationally rigid derivatives, is in the form 3 J C,H = 4.44 cos 2 Φ − 1.06 cos Φ + 0.45, with J (0°) = 3.83, J (60°) = 1.03, and J (180°) = 5.95 Hz. The 3 J C,H values of 5.15 and 2.95 Hz measured for H-4′C-4′S-4′C-1H-1 of methyl 4-thio-α-maltoside differ from those predicted from the conformation in the crystal. The calculated average 3 J C,H values, using PCILO-calculated abundances of conformers in aqueous solution, are 5.12 and 2.6 Hz, respectively.

A convenient method for S-glycosidic bond formation. Synthesis of p-lodophenyl 4′-thiomaltotrioside and its 2″,3″-unsaturated analogue

The axial trifluoromethanesulphonate group at C-4′ of acylated galactopyranosylglucopyranoside (11) was substituted by sulphur nucleophiles: selective S-deacetylation and activation of peracetylated 1-thio-α-D-glucose (12) led to p-iodophenyl 4′-thiomaltotrioside derivative (13); substitution by potassium thioacetate and S-deacetylation afforded 4′-thiomaltoside (17) which gave, by condensation with acetylated 1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol, under acidic conditions, as a major product the 2″,3″-unsaturated trisaccharide (19). The synthesis of compound (2), the sulphur positional isomer of (1), in 73% yield is also reported.

Conformational studies on l-amino-l-deoxypentitols☆☆☆

Abstract The conformations of the four 1-amino-1-deoxy- D -pentitols and their hydrochlorides in deuterium oxide solution have been analyzed by 250-MHz, 1 H-n.m.r. spectroscopy. The data indicate that the D - arabino ( 2 ) and D - lyxo ( 3 ) isomers adopt extended, planar, zigzag conformations, whereas the D - xylo ( 4 ) and D - ribo ( 1 ) isomers have the carbon chain in a nonplanar, “sickle” arrangement. The conformational assignments parallel closely those previously advanced for various related series of acetylated derivatives in organic solvents, and for nonacetylated analogs in solution and in the crystalline state. The spectral changes that take place in solution upon converting the amines 1–4 into their amine-salt forms are discussed, and the conformational data are considered in relation to the reactivity of 1–4 on deamination with nitrous acid and with respect to related reactions leading to ring closure under kinetic conditions.

Stereoselective thioglycoside syntheses. Part 6. Aryl 4-thiomalto-oligosaccharides as chromogenic substrates for kinetic studies with α-amylase

Nucleophitic bimolecular substitution, of either o- or p-nitrophenyl 2,3,6-tri-O-benzoyl-4-O-trifluoro-methylsulphonyl-α-D-galactopyranoside (1) or (2) with the sodium salt of 1-thio-α-D-glucopyranose in hexamethylphosphoramide afforded, after the usual deprotection sequences, o- and p-nitrophenyl 4-thio-α-maltosides (7) and (8). A similar synthetic scheme with (1) and the 1-α-thiolate of 4-thiomaltose (12) led to o-nitrophenyl 4,4′-dithio-α-maltotrioside (15). These 4-thio-oligosaccharides and their corresponding oxygen analogues were used, in comparative assays, as chromogenic substrates with porcine and human pancreatic α-amylases. In both series, enzymic velocity was higher for the maltotrioside derivatives than for the maltodisaccharides. o-Nitrophenyl glycosides behave as better substrates than the corresponding para isomers. Replacement of intersaccharide oxygen atoms by sulphur increased slightly the Michaelis constant, but had a negative effect on the hydrolysis rate. As a consequence, 4-thiomaltosylpligosaccharides were less sensitive substrates for pig pancreatic α-amylase as compared with their O-glycosyl counterparts. However, as the former class of compounds is split exclusively at the chromogenic site, they appear to be substrates of interest for direct kinetic studies with α-amylases.

Stereoselective thioglycoside syntheses. Part 4. A new approach to 1,4-linked 1-thio-disaccharides and a synthesis of thiomaltose

Two approaches are devised for the preparation of thiomaltose (16). Condensation between the sodium salt of 1-thio-α-D-glucopyranose (3) and methyl 2,3,6-tri-O-benzoyl-4-O-trifluoromethylsulphonyl-α-D-galactopyranoside (5) in hexamethylphosphoramide, leads to the methyl α-thiomaltoside derivative (6). On the other hand, the displacement of the C-4 trifluoromethanesulphonate of 1,6-anhydro-D-galactopyranose diacetate (13) by the sodium salt (3) gave the 1,6-anhydro-thio-disaccharide (14). The precursor of (13), 2,3-di-O-acetyl-1,6-anhydro-β-D-galactopyranose (12) was obtained in near quantitative yield from the known 2-O-acetyl-1,6-anhydro-3,4-O-isopropylidene-β-D-galactopyranose (9) by successive hydrolysis of the acetal group, orthoester formation (11), and selective opening of this intermediate through controlled acidic hydrolysis. Acetolysis of the methyl thio-maltoside (8) or the corresponding 1,6-anhydro-thio-disaccharide (14) followed by de-O-acylation afforded 4-S-α-D-glucopyranosyl-4-thio-D-glucopyranose [thiomaltose (16)] in excellent yields. 1,2,3,6-Tetra-O-acetyl-4-S-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-4-thio-β-D-glucopyranose (15), a useful precursor of thiomaltotriosyloligosaccharides, is also prepared from the acetolysis reaction.

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

Abstract 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.