M.Angeles Pradera

An easy route to seven-membered iminocyclitols from aldohexopyranosyl enamines

Abstract A new stereocontrolled and high yielding synthesis of biologically active polyhydroxyperhydroazepines is reported starting from easily available glycosylenamines (D- gluco , D- manno , and D- galacto configurations), which are transformed into 1,6-azaanhydropyranose derivatives. O - and N -Deprotection of the latter, followed by reduction with sodium cyanoborohydride, gives the target chiral iminocyclitols. The method is based on the capacity of the dialkoxycarbonylvinyl group to stabilize an amide ion, and the only limitation is the necessity for the starting glycosylenamine to have β-D-configuration. The inhibitory activity of several intermediate iminocyclitols and aldopyranosylenamines on different α- and β-glycosidases is also reported.

Isothiocyanato derivatives of sugars in the stereoselective synthesis of spironucleosides and spiro-C-glycosides

Abstract A stereocontrolled synthesis of pyranoid and furanoid spironucleosides and spiro- C -glycosides ( d - ribo and d - arabino configurations) of oxazolidines, oxazolines and perhydrooxazines via isothiocyanato sugar derivatives is reported. The intermediate isothiocyanates are prepared from sugar spiroketals by stereoselective opening of the acetal ring with trimethylsilyl N - and C -nucleophiles, and later formation of the isothiocyanato group.

Reactions of per-O-acetylglucosyl isothiocyanate with carbon bases. A new method for the stereocontrolled syntheses of nucleosides and glucosylaminothiophenes

Abstract Reaction of 2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyl isothiocyanate 5 with diethyl malonate in a basic medium gave the corresponding glucopyranosyl thioamide without significant deacetylation. This thioamide in solution presents Z-anti as the sole configuration. Reactions of 5 with carbanions which have an ethoxycarbonyl group are a way to prepare anomerically pure N -nucleoside derivatives of pyrrole and tetrahydropyridine. Reactions of 5 with carbanions stabilized by one cyano group are used to prepare glucosylamino thiophenes with only the β-configuration. Some other stereochemical aspects of the prepared compounds are discussed.

Isothiocyanatoulosonates, a new type of glycosyl isothiocyanate useful for the stereocontrolled synthesis of thiohydantoin spironucleosides

Abstract Thiohydantoin spironucleosides and N -alkyl, aryl and glycosyl derivatives are prepared in a stereocontrolled manner, by reaction of ammonia, and of alkyl-, aryl- and glycosyl-amines with a new class of isothiocyanato sugar: the methyl 2-deoxy-2-isothiocyanatohex-2-ulofura(pyra)nosonates. The reaction produces an intermediate thioureido derivative, which spontaneously cyclates to give the spironucleoside in high yield. Alternatively, the same spironucleosides are prepared from methyl 2-amino-2-deoxy-hex-2-ulofura(pyra)nosonates and alkyl-, aryl- and glycosyl isothiocyanates. Some of the prepared compounds have the structure of N -nucleoside of spirothiohydantoins.

Chiral thioxohydroimidazoles with two sugar moieties. N-, C-, and spiro-nucleosides

Abstract 2-Amino (alkyl and arylamino)-2-deoxy- d -fructose and different sugar isothiocyanates are used in the diastereoselective synthesis of chiral imidazolidine-2-thione N -nucleosides 12 – 23 . Water β-elimination of these compounds produces imidazoline-2-thione N -nucleosides 27 – 31 , whereas cyclodehydration of the same products gives, with high stereoselectivity, chiral spironucleosides with an N -glycosyl radical 34 – 37 . Conformational aspects of some of the prepared compounds are discussed.

Efficient synthesis of seven-membered iminocyclitols from glycosylenamines

Seven membered iminocyclitols are synthesized in four steps from easily available glycosylenamines (d-gluco, d-galacto, and d-manno configurations) through 1,6-aza-anhydrosugar derivatives. These intermediates are transformed into 2-hydroxy- and 2-unssbstituted azepanes depending on the reactants used for the cleavage of the ClO bond. The overally yields are high.

Glucosylenamines as glycosyl acceptors: synthesis of gentiobiosylenamines

The preparation of 2,3,4-tri-O-benzyl- (3), 2,3,4-tri-O-acetyl- (4), and 2,3,4-tri-O-benzoyl-N-(2,2-diethoxycarbonylvinyl)-6-O-trityl-beta- D-glucopyranosylamine (5) is described. The reaction of 3-5 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide yields 2,3,4-tri-O-benzyl- (9), 2,3,4-tri-O-acetyl- (10), and 2,3,4-tri-O-benzoyl-N-(2,2-diethoxycarbonylvinyl)-6-O-(2,3,4,6-tet ra-O- acetyl-beta-D-glucopyranosyl)-beta-D-glucopyranosylamine (11), respectively. 2,3,4-Tri-O-benzyl- (6), 2,3,4-tri-O-acetyl- (7), and 2,3,4-tri-O- benzoyl-N-(2,2-diethoxycarbonylvinyl)-beta-D-glucopyranosylamine (8) are also described.

Stereoselective synthesis of nucleoside analogues of chiral imidazolidines from sugar isothiocyanates

Abstract The syntheses of the disaccharide 5 and the trisaccharide 6 glycosyl isothiocyanates starting from di- or monosaccharide N -dialkoxycarbonylvinylglycosylamines 1 and 2 are described. Compounds 5, 6 , α- d -ribopyranosyl) and β-( d -glucopyranosyl, d -ribopyranosyl) isothiocyanates and 1,3,4,6-tetra- O -acetyl-2-deoxy-2-isothiocyanato-β- d -glucopyranose are used in the diastereoselective synthesis of the nucleoside analogues of (5 R )- and (5 S )-5-hydroxyimidazolidine-2-thiones 7, 11, 14, 16, 17, 18a, and 18b . The 5 R :5 S ratio depends on the anomeric configuration (configuration of C-2′ for 18a, 18b ) of the sugar isothiocyanate. β-Glycosyl isothiocyanates give mostly the (5 R )-epimer, whereas when a α-glycosyl isothiocyanate is used, there is practically no stereoselectivity.

Syntheses of O-protected 2-amino-2-deoxy-gentiobioside hydrohalides

Abstract The syntheses of ethyl 3,4-di-O-acyl(benzyl)-2-benzyloxycarbonylamino-2-deoxy-6-O-trityl-α-D-glucopyranosides (2–4) and methyl 3,4-di-O-acyl(benzyl)-2-deoxy-2-[(2′,2′-dimethoxycarbonylvinyl)amino]-6-O-trityl-α-D-glucopyranosides (12–14) are reported. The partially protected D-glucosamine derivatives ethyl 3,4-di-O-benzyl- (5) and 3-benzyl-2-benzyloxycarbonylamino-2-deoxy-α-D-glucopyranoside (6), ethyl 3,4-di-O-benzoyl-2-benzyloxycarbonylamino-2-deoxy-α-D-glucopyranoside (9), methyl 3,4-di-O-acyl(benzyl)-2-deoxy-2-dimethoxycarbonylvinylamino-α-D-glucopyranosides (15–17) have been prepared or isolated as by-products. The preparation of ethyl 3,4-di-O-acetyl- (18), 3,4-di-O-benzoyl-(19), and 3,4-di-O-benzyl-2-benzyloxycarbonylamino-2-deoxy-6-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) -α-D-glucopyranosides (20), and methyl 3,4-di-O-acetyl- (21), 3,4-di-O-benzoyl- (22), and 3,4-di-O-benzyl-2-deoxy-2-dimethoxycarbonylamino-6-O-(2,3,4,6-tetra-O-acetyl -β-D-glucopyranosyl)-α-D-glucopyranosides (23) through glycosylation reactions using 2, 3, 4, 12, 13, and 14 respectively as glycosyl acceptors and acetobromoglucose as glycosyl donor is described. The N-protecting group of 18, 19, and 21 was removed to give the alkyl hexa-O-acyl-2-amino-2-deoxy gentiobioside hydrohalides 24–26 respectively.

Stereoselective syntheses of 4-amino-aldoses, and chiral pyrrolidine derivatives from glycosylenamines

Abstract The stereocontrolled synthesis of N -protected 4-amino-4-deoxy- d -galacto- and - l -arabino-pyranoses starting from glycosylenamines via aza-anhydropyranoses is described. The steroselective transformation of the intermediate aza-anhydropyranoses into chiral pyrrolidines is also reported.