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A short and efficient route to enantiomerically pure hexahydroxy- and pentahydroxy-perhydroazaazulenes, ring-homologues of castanospermine, starting from the sole isoxazolidine derivative obtained in the 1,3-dipolar cycloaddition of a d -galactose-derived nitrone and methyl acrylate, is established. The procedure allows both backbone and stereochemical modulation of the products by choice of the starting monosaccharide. Structural assignment was based on crystallographic analysis of the starting isoxazolidine and NMR techniques. The products were tested for inhibitory activity against several glycosidases.

Methyl 2-benzamido-3,6-di- O -benzoyl-2,4-dideoxy-α- d -glucopyranoside-4- C -sulfonate sodium salt 9 and its galacto epimer 10 were prepared by oxidation with hydrogen peroxide in acetic acid of methyl 4- S -acetyl-2-benzamido-3,6-di- O -benzoyl-2-deoxy-4-thio-α- d -glucopyranoside 7 and its galacto epimer 8 , respectively. The 4-thioglucoside 7 was prepared from methyl 2-benzamido-3,6-di- O -benzoyl-2-deoxy-α- d -glucopyranoside by double inversion through triflation, inversion at C-4 with NaNO 2 , triflation of the resulting methyl 2-benzamido-3,6-di- O -benzoyl-2-deoxy-α- d -galactopyranoside, followed by displacement with potassium thioacetate. Deacylation of 9 with refluxing aqueous sodium hydroxide followed by deionisation yielded methyl 2-amino-2,4-dideoxy-α- d -glucopyranoside-4- C -sulfonic acid 11 . Deacylation of the galactopyranoside 10 under the same conditions also gave 11 , due to base catalysed isomerisation of galacto to the more stable gluco configuration. The structure of 11 , crystallized as the monohydrate, was confirmed by X-ray crystallographic analysis. The asymmetric unit contains two sugar molecules in two unique but similar conformations and two water molecules. The sulfo and the amino groups form a zwitterion, with each ammonium group hydrogen bonded to the sulfonate groups of two other molecules related by symmetry.

The novel 6-deoxy-6-C-sulfo- d -galactose (6-sulfofucose) potassium salt was prepared by oxidation of 1,2,3-tri-O-acetyl-6-S-acetyl-4-O-benzoyl-6-deoxy-α- d -galactopyranose with hydrogen peroxide and potassium acetate in acetic acid. Its cyclohexylammonium salt underwent a spontaneous conversion into 1-cyclohexylamino-1,6-dideoxy- d -tagatofuranose-6-C-sulfonic acid 4 through an Amadori rearrangement. 6-Deoxy-6-C-sulfo- d -glucose (sulfoquinovose) and 6-deoxy-6-C-sulfo- d -galactose were transformed into the corresponding 6-deoxy-6-C-sulfoalditols and 1-amino-1,6-dideoxy-6-C-sulfoalditols by reduction and reductive amination, respectively. The α anomeric configuration of 4, crystallised as the monohydrate, was assigned by X-ray crystallographic analysis. A conformation between E5 and 4T5 for the sugar ring, stabilised by a strong intramolecular hydrogen bond between NH and O-4, was observed.

Protected C7 and C8 aminodialdoses were prepared stereoselectively from readily available C5 and C6 monosaccharide N-benzyl nitrones, by regio- and diastereoselective 1,3-dipolar cycloaddition reactions with vinyl trimethylsilane, followed by acetyl chloride-mediated cleavage of the 5-(trimethylsilyl)isoxazolidine formed. The cycloaddition reaction took place in moderate to good global yields (67–74%); estimation of diastereoselectivities from isolated yields showed total endo preference for the reaction of the d -galacto configured nitrone and high endo preference for the d -ribo analogue, but exo preference for the d -xylo configured substrate. Attack on the re face of the nitrone was predominant in all cases. The absolute configuration of one of the protected 3-(α- d -galacto-pentopyranos-5-yl)isoxazolidine products was assigned by X-ray crystallographic analysis, allowing correlation of the configuration at the new stereogenic centre in the corresponding aminodialdose. For non-crystalline isoxazolidines, configurations were assigned on the basis of NOESY experiments and/or chemical correlation. Combined yields of aminodialdoses coming from isoxazolidines having identical configuration at C(3) sometimes reached high values (up to 90%). These compounds are precursors of higher-chain glycosamino acids.

Novel, potentially bioactive, fluorinated branched-chain monosaccharides were obtained by reaction of diethylaminosulphur trifluoride (DAST) with a series of methyl 3-C-cyano-3-ethoxycarbonyl-β- d -glucopyranoside derivatives, including the 4,6-O-benzylidene derivative and their 3-C-(N-protected aminomethyl) reduction products, as well as the phenyl 3-C-cyano-3-ethoxycarbonyl-1-thio-α- d -(and β- d -)glucopyranosides. The absolute configuration at C(3) was unambiguously assigned for all compounds on the basis of X-ray crystallographic analysis of methyl 4,6-O-benzylidene-3-C-cyano-3-deoxy-3-ethoxycarbonyl-β- d -glucopyranoside, corroborating the previous tentative assignment by other authors for the 4,6-unprotected compound. The course of the fluorination depended on the reaction temperature and the substitution pattern of the substrate. Thus, for methyl 3-C-cyano-3-ethoxycarbonyl-β- d -glucopyranoside, fluorination occurred exclusively at C(6), but for the phenylthio analogue, a 2-deoxy-2-phenylthio-α- d -manno-configured glycosyl fluoride and its 6-fluoro derivative were obtained, resulting from the expected rearrangement reaction, whilst starting from the phenylthio α anomer, only the unrearranged 6-fluoro compound was formed. Rearrangement was also observed in the fluorination of methyl 4,6-O-benzylidene-3-C-(N-protected aminomethyl)-β- d -glucopyranoside, which led to the 2-O-methyl-α- d -mannopyranosyl fluoride derivative as the sole product. This methodology may constitute a simple route to enantiopure conformationally constrained cyclic fluorinated β-amino acids having the α carbon atom shared with a pyranose ring, although only moderate yields were achieved, particularly in the fluorination step.

The crystal and molecular structure of (4R, 5R)-4-(1', 2', 3', 4', 5'-penta-O-acetyl-D-manno-pentitol-1-yl)-5-[N-(4-methoxyphenyl)carbamoyl]-2-(N-methyl-benzylamino)-3-nitro-5-phenyl-4,5-dihydrothiophene {IUPAC name: 1-(2R,3R)-5-(N-benzyl-N-methylamino)-2-[N-(4-methoxyphenyl)carbamoyl]-4-nitro-2-phenyl-2,3-dihydro-3-thienyl]-1,2,3,4,5-penta-O-acetyl-D-manno-pentitol}, C 41 H 45 N 3 O 14 S, has been investigated at 150K. The analysis of the crystal structure allows the definition of the absolute configuration of the products of the cycloaddition reaction between 3,5-diphenyl-2-(N-methylbenzylamine)-1,3-thiazolium-7-olate and (E)-3,4,5,6,7-penta-O-acetyl-1,2-dideoxy-1-C-nitro-D-manno-hept-1-enitol, where only one of the two diastereoisomeric dihydrothiophenes could be isolated. The configurations at the new C4 and C5 stereocentres, with respect to that known at C6, are R,R. Except for a slight overall contraction and a slightly altered geometry of the terminal acetyl group, the structure is virtually the same as at room temperature.

Mixed crystals of methyl 3-deoxy-3- C -methyl-3-nitro-α- d - and β- l -glucopyranosides (1:1), easily available from d -glucose by means of the Baer reaction, were completely characterised by X-ray diffraction analysis. These diastereomeric components, separation of which could be achieved through their 4,6- O -benzylidene derivatives, were selectively fluorinated at position 6 by treatment with DAST and stereoselectively transformed into phenyl 3-deoxy-3- C -methyl-3-nitro-1-thio-β- d -glucopyranoside and phenyl 3-deoxy-3- C -methyl-3-nitro-1-thio-β- l -glucopyranoside, respectively. Fluorination with DAST of each pure enantiomer afforded, depending on the conditions, the corresponding enantiomeric phenyl 3,6-dideoxy-6-fluoro-3- C -methyl-3-nitro-1-thio-β- d - and β- l -glucopyranosides or the respective rearranged 2,3,6-trideoxy-6-fluoro-3- C -methyl-3-nitro-2-phenylthio-α- d - and α- l -mannopyranosyl fluorides. This route constitutes a simple method for obtaining fair-to-good yields of 6-fluorinated branched-chain d - and l -sugar derivatives, potentially useful as glycosyl donors, starting from d -glucose.

Cycloaddition reactions of nitrones, including sugar nitrones, with nitroalkenes, including sugar nitroolefins, led with complete regioselectivity and stereospecificity to 4,5- trans -4-nitroisoxazolidines in 51–78% global yields. The endo/exo stereoselectivity depends on the type of sugar derivative used. As expected, the best π-diastereofacial selectivity was observed when both partners were sugar derivatives. Isomerisation of the first formed diastereomers by the action of silica gel was observed in some cases. Absolute configurations for two crystalline products were assigned by X-ray diffraction methods.

2-Amino-2,3-dideoxy- d -glucitol-3-sulfonic acid (3) and 2-amino-2,6-dideoxy- d -glucitol-6-sulfonic acid (4) were prepared by reduction of 2-amino-2,3 (and 2,6)-dideoxy- d -glucopyranose-3 (and 6)-sulfonic acids with sodium borohydride. The crystal structure of 4 monohydrate (C 6 H 15 NO 7 S · H 2 O) is orthorhombic, space group P 2 1 2 1 2 1 with unit cell dimensions a = 8.289(2), b = 24.548(5), and c = 5.149(2) A . A planar zig-zag conformation is observed in which N-2 and O-4 atoms are aligned 1,3-parallel, stabilized by an intramolecular hydrogen bond (N-H … O–4). The sulfo and the amino group form a zwitterion and two conformations are found for the ammonium group.

Methyl 2-amino-2-6-dideoxy-α- d -glucopyranoside-sulfonic acid (8) was prepared by oxidation of methyl 3,4-di-O-acetyl-6-S-acetyl-2-benzamido-2-deoxy-6-thio-α- d -glucopyranoside with hydrogen peroxide in acetic acid followed by N- and O-deacylation with aqueous sodium hydroxide. Compound 8 was also obtained by oxudation of methyl 3,4-di-O-acetyl-6-S-acetyl-2-deoxy-2[(2,2-dimethoxycarbonyl-vinyl) amino]-6-thio-α- d -glucopyranoside followed by deacetylation with Amberlite IR-120 (H+) resin. An X-ray analysis of 8, crystallised as a dihydrate, was carried out.

The crystal structure of the title compound, C40H43N3O13S, has been determined at room temperature and at 150 K. From the cyclo­addition of thio­isomunchnones with chiral nitro­alkenes, two diastereomeric di­hydro­thio­phenes were obtained, showing that regiospecificity and facial selectivity were involved in these cyclo­additions reactions where only one of the two diastereomeric di­hydro­thio­phenes could be isolated in the solid state. The chiralities of the two new centres at C4 and C5, determined with respect to that known at C6 are R,R. N—H⋯O hydrogen bonds join the mol­ecules in chains running along the c axis.

C 6 H 12 O 5 S cristallise dans P2 1 /c avec a=8,473, b=7,437, c=13,952 A, β=94,51°, Z=4; affinement jusqu'a R=0,038. Le cyclo oxathiane adopte une conformation chaise. Les deux substituants OCH 3 sont en positions trans. L'empilement des molecules est regi par des interactions de van der Waals

A new and regioselective synthesis of 6-oxopyrimidinium-4-olate systems (13–21) is described, involving the 1,3-dipolar cycloaddition of the 1,3-thiazolium-4-olate 12 with arylisocyanates. MNDO and AM1 calculations rationalise the reactivity and regioselectivity experimentally observed.

Thioisomunchnones undergo 1,3-dipolar cycloaddition with chiral nitroalkenes to afford stereoselectively 4,5-dihydrothiophenes by means of an unprecedented fragmentation of cycloadducts; the structures of these products have been established by single crystal X-ray structure analyses.

2-Amino-2,3-dideoxy- d -glucitol-3-sulfonic acid (3) and 2-amino-2,6-dideoxy- d -glucitol-6-sulfonic acid (4) were prepared by reduction of 2-amino-2,3 (and 2,6)-dideoxy- d -glucopyranose-3 (and 6)-sulfonic acids with sodium borohydride. The crystal structure of 4 monohydrate (C 6 H 15 NO 7 S · H 2 O) is orthorhombic, space group P 2 1 2 1 2 1 with unit cell dimensions a = 8.289(2), b = 24.548(5), and c = 5.149(2) A . A planar zig-zag conformation is observed in which N-2 and O-4 atoms are aligned 1,3-parallel, stabilized by an intramolecular hydrogen bond (N-H … O–4). The sulfo and the amino group form a zwitterion and two conformations are found for the ammonium group.

The crystalline potassium salt of a hexameric form of malondialdehyde has been obtained and shown to be racemic potassium hydrogen bis [trans-4-(1,3-dioxopropan-2-yl)-5-formyl-2-hydroxy-3,4-dihydro-2H-pyran].

1,4-Dimethyl-3-(D-galacto-pentitoll-yl)-5-(P-tolyl)pyrazole (2) was synthesised’ by the reaction of formaldehyde tolylhydrazone, generated in situ, with 1,2-dideoxy-lnitro-D-galucto-hept-I-enitol (1). 4-(Penta-O-acetyl-~-gu~~c~~-~ntitol-l-yl)-l-phenylpyrazole has been studied by X-ray crystallography’. Compound 2 and related compounds are of interest as intermediates in the synthesis of C-nucleosides’.

The structure of (4 R )-1-aryl-5-hydroxy-4-( d - arabino -tetritol-1-yl)imidazolidine-2-thiones ( 1–3 ), obtained by reaction of 2-amino-2-deoxy- d -glucose with aryl isothiocyanates, has been confirmed by 1 H- and 13 C-n.m.r. spectroscopy. Likewise, the structures of 2-(3-benzoylthioureido)-2-deoxy- d -glucopyranose and 2-deoxy-2-(3-phenylureido)- d -glucopyranose, prepared by reaction of 2-amino-2-deoxy- d -glucose with benzoyl isothiocyanate and phenyl isocyanate, respectively, were also established. An X-ray analysis of 1 –5 R (aryl = phenyl) has been carried out and its conformation in the solid state is one of the preponderant conformations in solution.

Methyl 3,6-dideoxy-3- C -methoxycarbonyl-3- C -nitro-α- l - galacto -hexopyranoside ( 3 ) has been synthesised by periodate oxidation of methyl α- l -rhamnopyranoside followed by condensation with methyl nitroacetate, and its structure has been established on the basis of its analytical and spectral data, and by an X-ray diffraction study. Crystals of 3 are orthorhombic, space group P 2 1 2 1 2 1 , with a = 10.009(3), b = 15.3610(3), c = 7.986(3) A, and Z = 4. Molecular-packing analysis in the atom—atom approach yields an equilibrium configuration in good agreement with the experimental findings.

The compound (C15H23NO7) crystallizes in the orthorhombic space group P212121 (a = 12.330(1) Å, b = 20.460(2) Å, c = 6.753(1) Å, Z = 4, D c = 1.284, and D m = 1.29 Mgm−3 (mixture of bromobenzene and ethanol) T = 293 K. R(F) = 0.043 for 1325 observed hkl). Torsion angles confirm the E configuration along the C6–C7 double bond. The pyranose ring adopts a twistboat conformation and the two dioxolane rings adopt different conformations, envelope and twist. The dihedral angles between the pyranose and dioxolane rings leastsquares planes are 83.9(2)° and 101.1(2)°. The molecule has an intramolecular hydrogen bond between the C and O atoms of the pyranose and the dioxolane rings. The crystal cohesion is stabilized by van der Waals forces.

Preliminary Weissenberg photographs, showed that crystals of the title compound (C22H26N2O2), belonged to the orthorhombic system with systematic absences consistent with the space group P212121. The unit-cell dimensions and their standard deviation, obtained at room temperature (293 K) were a = 10.583(6) Å, b = 18.812(2) Å, c = 9.962(1) Å, Z = 4. The unit cell volume (V) was 1983(1) Å3 and the absorption coefficient (μ) was 0.075 mm−1, D c was 1.174 and Dm measured by flotation was 1.18 Mgm−3; F(000) = 752, λ (MoKα ) = 0.7107 Å. The structure was solved by direct methods and refined by full-matrix least squares methods to a final R(F) = 0.041 and Rw(F 2) = 0.12. This work unambiguously establishes the overall conformation of the title molecule and the configuration for the new chiral centre C2 is R. The pyrrolidine ring adopts a perfect envelope 2 E conformation. Crystal cohesion is only governed by van der Waals contacts.

The configurations around the chiral centres C53, C52, C51 and C5 are R, S, R and R, respectively, corresponding to a D-arabino conformation. The tetrahydrotetrazine ring has a conformation close to that of a half-boat. Packing of the molecules is governed by normal van der Waals contacts

The thiazolidine ring in the title compound has an envelope conformation, E 4 , with a C atom out of the plane of the ring. The C-S and C-N bond lengths clearly show the typical resonance of the thiourea group. The molecules are linked by van der Waals forces and an intramolecular N...N hydrogen bond is present

This work unambiguously establishes the overall conformation of the title molecule, C 36 H 37 N 3 O 9 S, which includes a thiirane ring. The configuration is α-D-glucofuranose with the furanosyl ring T 4 3 ; the imidazolidine-2-one group assumes a form in which the fused C2' atom deviates by 0.14 A from the best plane

The PII proteins from the cyanobacteria Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803 have been crystallized and high-resolution structures have been obtained using X-ray crystallography. The core of these new structures is similar to that of the PII proteins from Escherichia coli, although the structures of the T- and C-loops differ. The T-loop of the Synechococcus protein is ordered, but appears to be stabilized by crystal contacts. The same loop in the Synechocystis protein is disordered. The C-terminus of the Synechocystis protein is stabilized by hydrogen bonding to the same region of a crystallographically related molecule. The same terminus in the Synechococcus protein is stabilized by coordination with a metal ion. These observations are consistent with the idea that both the T-loop and the C-terminus of PII proteins are ¯exible in solution and that this ¯exibility may be important for receptor recognition. Sequence comparisons are used to identify regions of the sequence unique to the cyanobacteria

C 6 H 12 O 5 S cristallise dans P2 1 /c avec a=8,473, b=7,437, c=13,952 A, β=94,51°, Z=4; affinement jusqu'a R=0,038. Le cyclo oxathiane adopte une conformation chaise. Les deux substituants OCH 3 sont en positions trans. L'empilement des molecules est regi par des interactions de van der Waals

CIsHI6N204, triclinic, P1, a = 12.719 (3), b= 7.485 (2), c= 7.728 (2) A, a =93"18 (2), fl = 100-40 (2), 3' = 99-24 (2) °, V = 711-5 (3) •3, Z = 2, Dm = 1.35, Dx = 1.34 Mg m -3, A(Mo Ka) = 0.7107/~, /.+ = 0"092 mm-~, F(000) = 304, T= 300 K, final R = 0.08 for 1124 observed reflections. The IR, Raman and ~H NMR spectra of 2,2- diacylethenamines and 2-aminomethylene-5,5- dimethylcyclohexane-l,3-diones show that these substances exist exclusively in the chelated enaminodiketone form and that the conjugated system contained in them is essentially planar [G6mez-Sfinchez, Garcia Martin, Borrachero & Bellanato (1987). J. Chem. Soc. Perkin Trans. 2, pp. 301-306]. The molecule has an intramolecular hydrogen bond between the N(amino) and O(carbonyl) atoms. The packing of the molecules is governed by normal van der Waals contacts

The solid-state conformation of the title compound, C 23 H 29 NO 10 , has been unequivocally established. The configuration at C1 is β-D-glucopyranose and the pyranose ring is essentially a perfect chair. Only the E rotamer along the N-C bond is observed.

Thioisomunchnones undergo 1,3-dipolar cycloaddition with chiral nitroalkenes to afford stereoselectively 4,5-dihydrothiophenes by means of an unprecedented fragmentation of cycloadducts; the structures of these products have been established by single crystal X-ray structure analyses.

The reaction of 2-amino-2-deoxy- d -glucose hydrochloride with 5,5-dimethyl-2-phenylaminomethylene-1,3-cyclohexanedione in MeOH in the presence of Et3N afforded 2-deoxy-2-[(4,4-dimethyl-2,6-dioxocyclohexylidenemethyl)amino]- d -glucose (6) in yields > 75%. Glycosidation of 6 with different alcohols (MeOH, CH2CHCH2OH, BnOH) under the Fischer conditions afforded mixtures of the corresponding alkyl 2-deoxy-2-[(4,4-dimethyl-2,6-dioxocyclohexylidenemethyl)-amino]-α,β- d -glucopyranoside and -α- d -glucofuranoside. Removal of the N-protecting group gave high yields of the free aminodeoxyglyco-pyranosides and -furanosides. In addition to other known glycosides, allyl and benzyl 2-amino-2-deoxy-α- d -glucopyranoside and ethyl and allyl 2-amino-2-deoxy-α-β-glucofuranoside were obtained. An X-ray crystallographic study of 6 indicated that, in the solid state, it has the α- d configuration and that the pyranoside ring adopts the 4C1 conformation.

Raney nickel reduction of (3R)-2-hydroxyimino-3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-gluco-pentitol-1-yl)-3,5,6,7-tetrahydrobenzofuran-4(2H)-ones (5) gives (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-galaco-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-ones (6) in high yields. Deacetylation of compounds (6) with catalytic sodium methoxide in methanol affords the corresponding (pentitol-1-yl)indolones (7). Compounds (6) can be transformed into the 3-(1,2,3,4,5-penta-O-acetyl-D-galacto- or -D-gluco-pentitol-1-yl)-1,5,6,7-tetrahydroindol-4-ones (8) by treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The structure of (3S)-3-(1,2,3,4,5-penta-O-acetyl-D-galacto-pentitol-1-yl)-1,2,3,5,6,7-hexahydroindol-4-one (6a) was confirmed by an X-ray structure determination.