Synthesis of C-5-thioglycopyranosides and their sulfonium derivatives from 1-C-(2'-oxoalkyl)-5-S-acetylglycofuranosides

1-C-(2'-oxoalkyl)-5-S-acetylglycofuranosides of L-arabinose, D-ribose, and D-xylose were converted to 1-C-(2'-oxoalkyl)-5-thioglycopyranosides by base treatment. The transformation was achieved through beta-elimination to an acyclic alpha,beta-conjugated aldehyde (ketone or ester), followed by an intramolecular hetero-Michael addition by the 5-thiol group. The cycloaddition was highly stereoselective in favor of an equatorial 1-C-substitution. The resultant C-5-thioglycopyranosides were further converted to the sulfonium salts by treatment with cyclic sulfate and methyl iodide. Two sulfonium isomers were obtained due to the presence of both S-axial and S-equatorial substitutions. We observed that the chemical shifts of both C-1 and C-5 in the S-axial substituted sulfonium sugars are always shifted up-field (5-10 ppm) in comparison to those in the S-equatorial substitutions (deltaC 49-53 ppm vs 42-45 ppm at C-1 and 37-42 ppm vs 32-35 ppm at C-5), which provides an easy way for determination of the stereochemistry.     

X-ray crystallographic and high-resolution NMR spectroscopy characterization of 4,6-di-O-acetyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranosyl sulfamide

Single crystal X-ray diffraction and high-resolution ¹H and ¹³C NMR spectral data for 4,6-di-O-acetyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranosyl sulfamide, a selective inhibitor of carbonic anhydrase isozyme IX, are reported. The ⁰H₅ was found to be the preferred form for this glycosyl sulfamide, both in the crystal lattice and in solution.     

Synthesis, the crystal structure, and high-resolution NMR spectroscopy of methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-alpha-D-arabino-hexopyranoside

Selective tosylation followed by acetylation of methyl 3-azido-2,3-dideoxy-alpha-D-arabino-hexopyranoside (1) in pyridine at room temperature affords a mixture of methyl 4-O-acetyl-3-azido-2,3-dideoxy-6-di-O-p-tolylsulfonyl-alpha-D-arabino-hexopyranoside (4) and methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-alpha-D-arabino-hexopyranoside (3). Compound 4 undergoes nucleophilic displacement with sodium iodide in acetic anhydride to give methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-alpha-D-arabino-hexopyranoside (7), whose crystal structure and (1H) and (13)C NMR data are reported. This compound adopts the 4C(1) conformation.     

Physicochemical and biological properties of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose (6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin)

A unique multibranched cyclomaltooligosaccharide (cyclodextrin, CD) of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose [6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin, (G(2))(3)-betaCD] was prepared. The physicochemical and biological properties of (G(2))(3)-betaCD were determined together with those of monobranched CDs (6-O-alpha-D-glucopyranosyl-alpha-cyclodextrin (G(1)-alphaCD), 6-O-alpha-D-glucopyranosyl-beta-cyclodextrin (G(1)-betaCD), and 6-O-alpha-maltosyl-beta-cyclodextrin (G(2)-betaCD)). NMR spectra of (G(2))(3)-betaCD were measured using various 2D NMR techniques. The solubility of (G(2))(3)-betaCD in water and MeOH-water solutions was extremely high in comparison with nonbranched betaCD and was about the same as that of the other monobranched betaCDs. The formation of an inclusion complex of (G(2))(3)-betaCD with stereoisomers (estradiol, retinoic acid, quinine, citral, and glycyrrhetinic acid) depends on the cis-trans isomers of guest compounds. The cis isomers of estradiol, retinoic acid, and glycyrrhetinic acid were included more than their trans isomers, while the trans isomers of citral and quinine fit more tightly than their cis isomers. (G(2))(3)-betaCD was the most effective host compound in the cis-trans resolution of glycyrrhetinic acid. Among the branched betaCDs, (G(2))(3)-betaCD exhibited the weakest hemolytic activity in human erythrocytes and showed negligible cytotoxicity in Caco-2 cells up to 200 microM. These results indicate unique characteristics of (G(2))(3)-betaCD in some biological responses of cultured cells.     

Synthesis of cis-(1-->3)-glycosides of allyl 2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside

Syntheses of allyl 2,3,4-tri-O-benzyl-alpha-D-gluco- and D-galactopyranosyluronate-(1-->3)-2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside via oxidation of the hydroxymethyl group of allyl 2,3,4-tri-O-benzyl-alpha-D-gluco- and D-galactopyranosyl-(1-->3)-2-acetamido-4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranoside under Jones conditions are described. Structures of the title compounds were confirmed by (1)H and (13)C NMR spectroscopy.     

Synthesis of new 2-C-(2,3:5,6-di-O-isopropylidene)-beta-D-mannofuranosyldithioacetate derivatives

Various new C-glycosides have been synthesized through the thioacylation reaction of different amines by a 2-C-mannofuranosyldithioacetate. Amino acids, di- and polyamines (putresceine, spermine, spermidine) and one amino alcohol were in particular used to generate glycothiopeptidic or precursors of "bola" structures.     

Synthesis and structure of selected quaternary N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol-5-yl)ammonium salts

The syntheses have been developed for quaternary N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol-5-yl)ammonium salts derived from five aromatic amines, pyridine, 2-methylpyridine, 3-carbamoylpyridine, 4-(N,N-dimethylamino)pyridine, and quinoline, as well as two tertiary aliphatic amines, trimethylamine and triethylamine. Reactions of 1,4-anhydro-2,3-O-isopropylidene-5-O-tosyl-D,L-ribitol with tri-n-propylamine and tri-n-butylamine were unsuccessful. The products were identified on the basis of their 1H and 13C NMR spectra. The structure of N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol-5-yl)trimethylammonium tosylate was additionally elucidated by X-ray diffractometry.     

Facile synthesis and cytotoxicity of triterpenoid saponins bearing a unique disaccharide moiety: hederacolchiside A1 and its analogues

An improved synthetic approach toward hederacolchiside A1, an antitumor triterpenoid saponin bearing a unique disaccharide moiety, was established. This approach began from a partially protected intermediate and avoided tedious protection-deprotection manipulation. An abnormal ring conformation (1C4) of the center arabinose residue was found in the intermediate, which may account for the unusual regioselectivity between 3-OH and 4-OH of arabinose. Two analogues of hederacolchiside A1 were then facilely prepared by this approach and exhibited significant cytotoxicity in preliminary in vitro assay.     

Preparation, single-crystal X-ray diffraction and high-resolution NMR spectroscopic analyses of N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]trimethylammonium iodide

The synthesis and isolation of 1,4-anhydro-5-deoxy-5-iodo-2,3-O-isopropylidene-D,L-ribitol and N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]trimethylammonium iodide are described. The products were examined by (1)H, (13)C NMR spectroscopy, and N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]trimethylammonium iodide was additionally analyzed by X-ray crystallography.     

X-ray diffraction and high-resolution NMR spectroscopy of methyl 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enopyranuronate

Single-crystal X-ray diffraction and high-resolution (1)H and (13)C NMR spectral data for methyl 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enopyranuronate are reported. The (5)H(4) conformation was found to be the preferred form for this glycal, both in the crystal lattice and in solution. The factors determining the (4)H(5)<==>(5)H(4) conformational equilibrium for acetylated glycals are discussed.     

Au(III)-complexes of the alanyl-containing peptides glycylalanine and glycylalanylalanine - Synthesis, spectroscopic and structural characterization

As part of an investigation on the coordination ability of peptides, the dipeptide glycylalanine (H-Gly-Ala-OH), tripeptide glycylalanylalanine (H-Gly-Ala-Ala-OH) and their Au(III)-complexes have been characterized structurally. The quantum chemical calculations and linear-dichroic infrared (IR-LD) spectroscopy predict structures of the compound studied, which are compared with a single crystal X-ray diffraction of H-Gly-Ala-OH. The coordination processes with Au(III) are supported by data for ¹H NMR, ESI-MS, HPLC-MS-MS, TGV and DSC methods. The [Au(Gly-Ala)H₋₁Cl] and [Au(Gly-Ala-Ala)H₋₂] · 2H₂O complexes are formed via -NH₂, N⁻amide/s and groups of the peptides. One Cl⁻ ion is attached to the metal center as terminal ligand in the first complex. In both cases a near to square-planar geometry of the chromophors AuN₂OCl and AuN₃O is yielded.     

Mammalian mitochondrial and microsomal cytochromes b(5) exhibit divergent structural and biophysical characteristics

The only outer mitochondrial membrane cytochrome b(5) examined to date, from rat (rOM b(5)), exhibits greater stability than known mammalian microsomal (Mc) isoforms, as well as a much higher kinetic barrier for hemin dissociation and a more negative reduction potential. A BlastP search of available databases using the protein sequence of rOM b(5) as template revealed entries for analogous proteins from human (hOM b(5)) and mouse (mOM b(5)). We prepared a synthetic gene coding for the heme-binding domain of hOM b(5), and expressed the protein to high levels. The hOM protein exhibits stability, hemin-binding, and redox properties similar to those of rOM b(5), suggesting that they are characteristic of the OM b(5) subfamily. The divergence in properties between the OM and Mc b(5) isoforms in mammals can be attributed, at least in part, to the presence of two extended hydrophobic patches in the former. The biophysical properties characteristic of the OM proteins may be important in facilitating the two functions proposed for them so far, reduction of ascorbate radical and stimulation of androgen synthesis.     

X-ray crystallography and solution NMR spectroscopy characterization of heptakis(2,3-di-O-acetyl-6-bromo-6-deoxy)cyclomaltoheptaose

Heptakis(2,3-di-O-acetyl-6-bromo-6-deoxy)cyclomaltoheptaose has been characterized in aqueous solution by 1D and 2D NMR spectroscopy and in the solid state by X-ray crystallography. In methanol solution, the acetyl groups were found to interact with both inward and outward-pointing protons. This and the strong deshielding of the bridging carbons, relative to the nonacetylated precursor, indicate macrocyclic flexibility. In the crystalline state the macrocycle exists as a methanol complex. It exhibits elliptical distortion, all glucose residues been tilted with their primary side toward the cavity. The existing strain due to the congestion of 14 acetyl groups at the secondary site is relieved by two glucose rings acquiring the rarely observed skew-boat conformation, (0)S(2), by the increased tilting of two glucose residues, as well as by minor variations of the torsion angles of the acetyl groups. The seven bromine atoms are quite accessible to nucleophiles.     

Synthesis and characterization of tetraphenylporphyrin iron(III) complexes with substituted phenylcyanamide ligands

Several five coordinate complexes of [(TPP)Fe^III(L)] in which TPP is the dianion of tetraphenylporphyrin and L is the monoanion of phenylcyanamide (pcyd) (1), 2,5-dichlorophenylcyanamide (2,5-Cl₂pcyd) (2), 2,6-dichlorophenylcyanamide (2,6-Cl₂pcyd) (3), and 2,3,4,6-tetrachlorophenylcyanamide (2,3,4,6-Cl₄pcyd) (4) have been prepared by the reaction of [(TPP)Fe^IIICl] with appropriate thallium salt of phenylcyanamide. Each of the complexes has been characterized by IR, UV-Vis and ¹H NMR spectroscopic data. Dark red-brown needles of [(TPP)Fe^III(2,6-Cl₂pcyd)] (C₅₁H₃₁Cl₂FeN₆ · CHCl₃) crystallize in the triclinic system. The crystal structure of Fe(III) compound shows a slight distortion from square pyramidal coordination with the 2,6-dichlorophenylcyanamide anion in the axial position through nitrile nitrogen atom. Iron atom is 0.47(1) Å out of plane of the porphyrin toward phenylcyanamide ligand. In non-coordinating solvents, such as benzene or chloroform, these complexes exhibit ¹H NMR spectra that are characteristic of high-spin (S = 5/2) species. The X-ray crystal structure parameters are also consistent with high-spin iron(III) complexes. The iron(III) phenylcyanamide complexes are not reactive toward molecular oxygen; however, these complexes react with HCl and produce TPPFe^IIICl.     

Synthesis of triphenyltin(IV) hydrosulfide

Compounds of the type R₃SnSH are believed to be unstable (unless sterically protected by very bulky R groups) because of their facile condensation into the corresponding sulfide, (R₃Sn)₂S. One such compound, Ph₃SnSH has been synthesized by an one pot reaction of triphenyltin hydroxide with thiophosgene followed by the hydrolysis of the intermediate triphenyltin chlorothioformate. The product, triphenyltin hydrosulfide has been characterized by IR, ¹H, ¹³C and ¹¹⁹Sn NMR spectral techniques. Single crystal X-ray analysis revealed that the molecule is a discrete monomer containing tin atom at the centre of a distorted tetrahedron. Plausible reaction mechanism for the formation of the molecule has also been reported.     

Synthesis and characterization of tetraphenylporphyrin manganese(III) complexes of phenylcyanamide ligands

Several complexes of TPPMn-L, where TPP is the dianion of tetraphenylporphyrin and L is monoanion of 4-methylphenylcyanamide (4-Mepcyd) (1), 2,4-dimethylphenylcyanamide (2,4-Me₂pcyd) (2), 3,5-dimethylphenylcyanamide (3,5-Me₂pcyd) (3), 4-methoxyphenylcyanamide (4-MeOpcyd) (4), phenylcyanamide (pcyd) (5), 2-chlorophenylcyanamide (2-Clpcyd) (6), 2,5-dichlorophenylcyanamide (2,5-Cl₂pcyd) (7), 2,6-dichlorophenylcyanamide (2,6-Cl₂pcyd) (8), 4-bromophenylcyanamide (4-Brpcyd) (9), and 2,3,4,5-tetrachlorophenylcyanamide (2,3,4,5-Cl₄pcyd) (10), have been prepared from the reaction of TPPMnCl and thallium salt of related phenylcyanamide. Each of the complexes has been characterized by IR, UV-Vis and ¹H NMR spectroscopies.4-Methylphenylcyanamidotetraphenylporphyrin manganese(III) crystallized with one molecule of solvent CHCl₃ in the triclinic crystal system and space group with the following unit cell parameters of: a = 11.596(6) Å; b = 11.768(9) Å; c = 17.81(2) Å; and α, β, γ are 88.91(9)°, 88.16(7)°, 67.90(5)°, respectively; V = 2251(3) Å³; Z = 2. A total of 4234 reflections with I > 2σ(I) were used to refine the structure to R = 0.0680 and R_w = 0.2297. The Mn(III) shows slightly distorted square pyramidal coordination with the 4-methylphenylcyanamide in the axial position, coordinated from nitrile nitrogen. The reduction of each of the TPPMn-L complexes was also examined in dichloromethane and spectroelectrochemical behavior of (1) was investigated and compared to TPPMnCl.     

Carbon fixation and carbonic anhydrase activity in Haslea ostrearia (Bacillariophyceae) in relation to growth irradiance

The metabolic pathway of primary carbon fixation was studied in a peculiar pennate marine diatom, Haslea ostrearia (Bory) Simonsen, which synthesizes and accumulates a blue pigment known as “marennine”. Cells were cultured in a semi-continuous mode under saturating [350 μmol(photon) m⁻² s⁻¹] or non-saturating [25 μmol(photon) m⁻² s⁻¹] irradiance producing “blue” (BC) and “green” (GC) cells, characterized by high and low marennine accumulation, respectively. Growth, pigment contents (chlorophyll a and marennine), ¹⁴C accumulation in the metabolites, and the carbonic anhydrase (CA) activity of the cells were determined during the exponential growth phase. Growth rate and marennine content were closely linked to irradiance during growth: higher irradiance increased both growth rate and marennine content. On the other hand, the Chl a concentration was lower under saturating irradiance. The distribution between the Calvin-Benson (C₃) and β-carboxylation (C₄) pathways was very different depending on the irradiance during growth. Metabolites of the C₃ cycle contained about 70 % of the total fixed radioactivity after 60 s of incorporation into cells cultured under the non-saturating irradiance (GC), but only 47 % under saturating irradiance (BC). At the same time, carbon fixation by β-carboxylation was 24 % in GC versus about 41 % in BC, becoming equal to that in the C₃ fixation pathway in the latter. Internal CA activity remained constant, but the periplasmic CA activity was higher under low than high irradiance.     

Synthesis and structural characterization of dimolybdenum(IV) and molybdenum(VI) complexes with trisbenzenethiolatophosphine ligands

The synthesis and crystal structures of two high valent molybdenum complexes containing trisbenzenethiolatophosphine ligands, [Mo₂(PS3)₂(PS3H)] (1) and [Mo(PS3″)₂] (2), where PS3 = [P(C₆H₄-2-S)₃]³⁻, PS3H = [P(C₆H₄-2-S)₂(C₆H₄-2-SH)]²⁻, and PS3″ = [P(C₆H₃-3-Me₃Si-2-S)₃]³⁻, are described. Compound 1 is a dimeric Mo(IV) species containing three PS3 ligands with an uncoordinated thiol group. An intramolecular hydrogen bonding S-H?S was found in the structure. Two molybdenum ions are bridged by three thiolates. The geometry can be described as two pentagonal bipyramids sharing a triangle face formed by three bridging S atoms. Compound 2 is a Mo(VI) species binding with two tetradentate PS3″ ligands. The eight-coordinate molybdenum center adopts a dodecahedral geometry.     

New 1-C-(5-thio-D-xylopyranosyl) derivatives as potential orally active venous antithrombotics

In the search for new orally active antithrombotic drugs that are metabolically stable, we explored the synthesis of 1-C-(5-thio-D-xylosyl) derivatives, examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl, alkylcarboxymethylenyl, arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C-linked analogues of 5-thio-D-xylopyranosides.     

Synthesis and spectroscopic and X-ray structural characterisation of some para-substituted triaryltin(pentacarbonyl)manganese(I) complexes

A series of para-substituted triaryltin(pentacarbonyl)manganese(I) compounds [(p-XC₆H₄)₃SnMn(CO)₅: II, X=CH₃; III, X=CH₃O; IV, X=CH₃S; V, X=F; VI, X=Cl; VII, X=CH₃S(O₂)] is reported for comparison with the known phenyl analogue I. IR data [ν(CO)] as well as complete ¹¹⁹Sn/⁵⁵Mn/¹³C solution NMR results are given for I-VII. Chemical shifts, ¹¹⁹Sn versus ⁵⁵Mn, except I, correlate well, but have differing single parameter (SP) correlations, ¹¹⁹Sn versus σ_I and ⁵⁵Mn versus σ°_p. These results are compared with previous SP studies of the ¹¹⁹Sn solution NMR spectra of the series, (p-XC₆H₄)₄Sn and (p-XC₆H₄)₃SnY (Y=Cl, Br, I). Full crystal structures are reported for compounds II-VI. All are similar to that of I, with the Mn(CO)₅ moiety being a distorted tetragonal pyramid, and having a quasi-mirror plane through the central C₄MnSnC₃ skeleton. The Ar₃Sn are distorted trigonal propellers with ring torsion angles in the range 30-80°, the exception being IV with one torsion angle of 22°.