New condensed indoline bis-spiropyrans

The synthesis of new condensed indoline bis-spiropyrans from isomeric hexamethyldihydroindolo-[4,5-e]-and -[7,6-g]indoles, and also from hexamethyldihydrobenzo[e]pyrrolo[3,2-g]indole in three stages has been generalized. By condensation of the isomeric bis-analogs of Fischer's bases obtained at the second stage with salicylic aldehydes, the following bis-spiro compounds have been synthesized: 6,6"-dinitro-, 6,6",8,8"-tetranitro-, 6,6",8,8"-tetrabromo-1',3',3',6',8',8'-hexamethyldispiro[chromene-2,2'-indolino[7,6-g]indoline-7',2"-chromenes], 6,6"-dinitro-, 6,6",8,8"-tetranitro-, 6,6",8,8"-tetrabromo-1',1',3',8',10',10'-hexamethyldispiro[chromene-2,2'-indolino[4,5-e]indoline-9',2"-chromenes], 6,6"-di-nitro-, 6,6"-dibromo-, and 6,6",8,8"-tetrabromo-1',1',8,8'-tetramethyl-1',4',5',8'-tetrahydrodispiro-[chromene-2,2'-dipyrrolo[1,2,3-d,e:3,2,1-i,j]benzo[g]quinoxaline-7',2"-chromenes].     

Asymmetric desymmetrization of 2,2',6,6'-tetrahydroxybiphenyl through annulation with enantiomerically pure bis(mesylate)

[formula: see text] 2,2',6,6'-Tetrahydroxybiphenyl undergoes a facile annulation reaction with bis(mesylate) derived from (S)-1,2-propanediol in the presence of Cs2CO3 to give the corresponding asymmetric desymmetrization product of S axial chirality with exclusive diastereoselectivity. The desymmetrization product can be utilized as a versatile chiral building block in asymmetric synthesis of axially chiral 6,6'-disubstituted 2,2'-biphenyldiols.     

Synthesis of Trideca-O-methyl-alpha-pedunculagin. Diastereo-Favoritism Studies on Intramolecular Ester-Cyclization of Axially Chiral Diphenic Acids with Carbohydrate Core

Total synthesis of trideca-O-methyl-alpha-pedunculagin was achieved by a simple sequence. The key step is the synthesis of methyl 4,6-O-benzylidene-2,3-O-[(S)-4,4',5,5',6,6'-hexamethoxydiphenoyl]-alpha-D-glucopyranoside through intramolecular ester-cyclization of racemic hexamethoxydiphenoyl chloride with methyl 4,6-O-benzylidene-alpha-D-glucopyranoside at the 2,3-position. The diastereoselectivity results obtained in the intramolecular cyclization of hexamethoxydiphenic acid to the carbohydrate core raises a very interesting point in considering the pathway of (R)-diphenic acid biosynthesis.     

Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA

Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.     

Synthesis of 6,6'-ether linked disaccharides from D-allose, D-galactose, D-glucose and D-mannose; evidence on the structure of coyolosa

6,6'-Linked ethers derived from D-allose, D-galactose, D-glucose, and D-mannose have been prepared in order to allow comparisons with the reported 6,6'-linked hexopyranose coyolosa, an hypoglycemic compound which has been isolated by extraction of the root of the palm Acrocomia mexicana. Comparison of NMR data from the ethers and their derived peracetates with corresponding reported data from coyolosa and its peracetate indicate that coyolosa is not a 6,6'-linked disaccharide. The synthesised compounds are representatives of a novel class of disaccharide derivatives which are linked tail to tail in contrast to the more usual head to tail(e.g. maltose) or head to head(e.g. trehalose) disaccharides.     

The synthesis and liquid crystal properties of certain 1-(4'-n-alkoxy-2,2',3,3',5,5',6,6'-octafluorobiphenyl-4-yl)- 2-(trans-4-n-pentylcyclohexyl)-ethanes and -ethenes

The synthesis and liquid crystal properties of eight members of the homologous series of 1-(4'-n-alkoxy-2,2',3,3',5,5',6,6'-octafluorobiphenyl-4-yl)-2-(trans-4-n-pentylcyclohexyl)-ethanes and eight members of the corresponding -ethanes, which have the E-configuration, are reported. These compounds are nematic, the ethenes having a considerably mesophase higher thermal stability than the analogous ethanes.     

Synthesis, characterization, and energetic properties of diazido heteroaromatic high-nitrogen C-N compound

The synthesis, characterization, and energetic properties of diazido heteroaromatic high-nitrogen C-N compound, 3,6-diazido-1,2,4,5-tetrazine (DiAT), are reported. Its normalized heat of formation (NDeltaHf), experimentally determined using an additive method, is shown to be the highest positive NDeltaHf compared to all other organic molecules. The unexpected azido-tetrazolo tautomerizations and irreversible tetrazolo transformation of DiAT are remarkable compared to all other polyazido heteroaromatic high-nitrogen C-N compounds, for example, 2,4,6-triazido-1,3,5-triazine; 4,4',6,6'-tetra(azido)hydrazo-1,3,5-triazine; 4,4',6,6'-tetra(azido)azo-1,3,5-triazine; and 2,5,8-tri(azido)-1,3,4,6,7,9,9b-heptaazaphenalene (heptazine).     

Asymmetric synthesis of axially chiral biaryls via desymmetrization of 2,2',6,6'-tetrahydroxybiphenyl using 1,4-Di-O-benzyl-L-threitol as a chiral template

Sequential etherification of 2,2',6,6'-tetrahydroxybiphenyl (1) with 1,4-di-O-benzyl-L-threitol under Mitsunobu conditions gives desymmetrized biphenyldiol 9 of S-axial chirality exclusively. Cyclization of 9 with 1,omega-dibromoalkanes followed by removal of the chiral auxiliary yields (S)-2,2'-biphenyldiols 14 with alkylenedioxy bridges at the 6 and 6' positions. (S)-6,6'-Dialkyl- and -diphenyldiols 20 are obtained in an efficient manner via Pd(0)-catalyzed cross-coupling of bis(triflate) derivative 17 with organozinc reagents. Bis(triflate) 17 also serves as an intermediate for asymmetric synthesis of axially chiral biphenyldicarboxylic acid 23, terphenylcarboxylic acid 28, lactone 26, and lactam 30.     

Bidirectional synthesis of the central amino acid of chloptosin

[reaction: see text] An efficient total synthesis of (2S,2'S,3aR,3'aR,8aR,8'aR)-6,6'-dichloro-3a,3'a-dihydroxy-1,1',2,2',3,3a,3',3'a,8,8a,8',8'a-dodecahydro-5,5'-bipyrrolo[2,3-b]indole-2,2'-dicarboxylic acid, the central amino acid component of chloptosin (1), is described. Starting from m-chloronitrobenzene, this C(2)-symmetrical amino acid was synthesized by using a 14-step route, in which a Zinin benzidine rearrangement, intramolecular Heck reaction, and selenocyclization and oxidative deselenation served as key steps. The absolute stereochemistry of the target was confirmed by X-ray single-crystal studies on a key intermediate (17).     

Improved synthesis of 2,2'-bipyrimidine

A high-yield synthesis was developed for the preparation of 2,2'-bipyrimidine (1) using the Ullmann coupling of 2-iodopyrimidine. The new procedure was also used for the preparation of 4,4',6,6'-tetramethyl-2,2'-bipyrimidine (2) and 5,5'-dibromo-2,2'-bipyrimidine (3).     

The first 5,6-dihydroxyindole tetramer by oxidation of 5,5',6,6'-tetrahydroxy- 2,4'-biindolyl and an unexpected issue of positional reactivity en route to eumelanin-related polymers

[structure: see text]. The first tetramer of the eumelanin precursor 5,6-dihydroxyindole has been obtained, as the acetyl derivative, by peroxidase/H2O2-induced oxidative coupling of 5,5',6,6'-tetrahydroxy-2,4'-biindolyl (2) in the presence of Zn2+ ions. The tetramer, 5,5',5',5',6,6',6',6'-octaacetoxy-2,4':2',3':2',4'-tetraindolyl (acetylated 7), incorporates an unprecedented 2,3'-biindolyl substructure suggestive of a different positional reactivity of the 5,6-dihydroxyindole system when framed into a dimeric scaffold.     

Highly Efficient Enantioselective Synthesis of Optically Active Dihydropyrones by Chiral Titanium(IV) (5,5',6,6',7,7',8,8'-Octahydro-1,1'-Bi-2-Naphthol) Complexes

The formal hetero-Diels-Alder reaction between 1-methoxy-3-(trimethyl-silyl)oxy-1,3-butadiene and aldehydes provides useful access to dihydropyrones, a class of compounds with extensive utility in organic synthesis. Asymmetric catalysis of this reaction has been previously reported by a number of investigators. Herein we wish to describe that chiral 5,5',6,6',7,7',8,8'-octahydro-1, 1'-bi-2-naphthol (H₈-BINOL)/Ti(O-i-Pr)₄ complexes are more effective catalysts than BINOL/Ti(O-i-Pr)₄ and others for the asymmetric hetero-Diels-Alder reactions.     

有机二磺酸二邻菲咯啉二水合锌配合物(英)

The crystal structure of [Zn(H₂O)₂(phen)₂][DBDA] (1) (DBDA=2,2′-dimethoxy-1,1′-binaphthylene-6,6′-disulfonate, phen=1,10-phenanthroline) involves the anion part (2,2′-dimethoxy-1,1′-binaphthylene-6,6′-disulfonate ) and the cation part which compose of a octahedron coordinated zinc center surrounded by two water and four nitrogen atoms from two phen rings, the 3D packing structure was formed through the strong H-bonding interaction between sulfonate and water. CCDC: 277923.     

New terpyridine-containing macrocycle for the assembly of dimeric Zn(II) and Cu(II) complexes coupled by bridging hydroxide anions and pi-stacking interactions

The synthesis of the new terpyridine-containing macrocycle 2,5,8,11,14-pentaaza[15](6,6' ')cyclo(2,2':6',2' ')terpyridinophane (L) is reported. The ligand contains a pentaamine chain linking the 6,6' ' positions of a terpyridine unit. A potentiometric, (1)H NMR, UV-vis spectrophotometric and fluorescence emission study on the acid-base properties of L in aqueous solutions shows that the first four protonation steps occur on the polyamine chain, whereas the terpyridine nitrogens are involved in proton binding only at strongly acidic pH values. L can form both mono- and dinuclear Cu(II), Zn(II), Cd(II), and Pb(II) complexes in aqueous solution. The crystal structures of the Zn(II) and Cd(II) complexes ([ZnLH](2)(micro-OH))(ClO(4))(5) (6) and ([CdLH](2)(micro-Br))(ClO(4))(5).4H(2)O (7) show that two mononuclear [MLH](3+) units are coupled by a bridging anion (OH(-) in 6 and Br(-) in 7) and pi-stacking interactions between the terpyridine moieties. A potentiometric and spectrophotometric study shows that in the case of Cu(II) and Zn(II) the dimeric assemblies are also formed in aqueous solution containing the ligand and the metals in a 1:1 molar ratio. Protonation of the complexes or the addition of a second metal ion leads to the disruption of the dimers due to the increased electrostatic repulsions between the two monomeric units.     

5,6-dihydroxyindole tetramers with "anomalous" interunit bonding patterns by oxidative coupling of 5,5',6,6'-tetrahydroxy-2,7'-biindolyl: emerging complexities on the way toward an improved model of eumelanin buildup

Chemical or enzymatic oxidation of 5,6-dihydroxyindole (1) leads to the rapid deposition of a black solid resembling eumelanin pigments by way of a complex oligomerization/polymerization process that proceeds in the early stages via dimers 2-3 and trimers 5-6 characterized by 2,4'- and 2,7'-couplings. Despite extensive efforts, the structures of the higher oligomers, which define the structural architecture and physicochemical properties of the eumelanin particles, have so far defied elucidation. Using a dimer-dimer coupling strategy that has recently allowed the first successful entry to a tetramer of 1, we report now three additional tetramers obtained by oxidation of 5,5',6,6'-tetrahydroxy-2,7'-biindolyl (3) with the peroxidase/H2O2 system. On the basis of extensive 2D NMR and mass spectrometric analysis, the products were identified as 5,5',5',5',6,6',6',6'-octaacetoxy-7,2':3',3':2',7'-tetraindolyl (acetylated 8, 3%), 5,5',5',5',6,6',6',6' '-octaacetoxy-2,7':4',4':7',2'-tetraindolyl (acetylated 9, 4%), and 5,5',5',5',6,6',6',6'-octaacetoxy-2,7':2',3':2',7'-tetraindolyl (acetylated 10, 5%), in which the inner units are linked through unexpected 3,3'-, 4,4'-, and 2,3'-linkages. If verified in further studies, the newly uncovered coupling patterns would entail important consequences for current models of eumelanin structure based on one-dimensional structural chains with extended pi-electron conjugation or pi-stacked flat oligomer aggregates.     

Coordination features of a terpyridine-containing polyamine receptor. Effect of protonation on the photophysical properties of the complexes

The synthesis of the new terpyridine-containing macrocycle 2,6,10,14-tetraaza[15](6,6')cyclo(2,2':6',2')terpyridinophane (L) is reported. The ligand contains a tetraamine chain linking the 6,6' positions of a terpyridine unit. A potentiometric, (1)H NMR, UV-vis spectrophotometric and fluorescence emission study on the basicity properties of in aqueous solutions shows that the first four protonation steps occur on the polyamine chain, while the terpyridine nitrogens are involved in proton binding only in the last protonation step at strongly acidic pH values. Cu(II), Zn(II), Cd(II) and Pb(II) complexation was studied in aqueous solution by means of potentiometric, spectrophotometric and spectrofluorimetric measurements. Cu(II) and Zn(II) can form both mono- and dinuclear complexes in solution, while the larger Cd(II) and Pb(II) give only mononuclear complexes. In the [ML](2+) complexes (M = Zn(II) or Cd(II)) the metal is unequivocally bound to the terpyridine unit. Some amine groups are not coordinated and can quench the fluorescence emission of the terpyridine unit thanks to an electron transfer process. Protonation of the unbound amine groups inhibits the eT process, affording fluorescent [MLH(x)]((2+x)+) complexes.     

4,4'-, 5,5'-, and 6,6'-dimethyl-2,2'-bipyridyls: the structures, phase transitions, vibrations, and methyl group tunneling of their complexes with chloranilic acid

The crystal and molecular structures of 4,4(')- and 6,6(')-dimethyl-2,2(')-bipyridyl complexes with 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (chloranilic acid, CLA) have been determined and compared with those of the complex with the 5,5(')-derivative, which is known to possess interesting antiferroelectric properties. In the crystalline state, all three compounds form hydrogen bonded chains with N(+)-H···O(-) and O-H···N bridges on both sides of the bipyridyl constituent. The comparison of three derivatives indicates that the N(+)-H···O(-) hydrogen bonds are shortest for the 5,5(')-dimethyl complex. The 4,4(')- and 6,6(')-derivatives do not show any ferroelectric feature. The 6,6(')-one is, however, characterized by a continuous phase transition, revealed in the differential scanning calorimetry, dilatometric, and dielectric characteristics. The tunneling splitting measured by neutron backscattering in the energy range ±30 μeV for the neat dimethyl bipyridyls and their complexes with CLA indicates that the different splittings are primarily due to the crystal packing effect and that charge transfer between interacting compounds plays only a minor role.     

消旋的有机二磺酸三邻菲咯啉锌配合物(英)

Compound [Zn(phen)₃][BDA] (1) (BDA=6,6′-dibromo-2,2′-dimethoxy-1,1′-binaphthylene-4,4′-disulfonate, phen= 1,10-phenanthroline) composes of the anion part (racemic-(R,S)-6,6′-dibromo-2,2′-dimethoxy-1,1′-binaphthylene-4,4′-disulfonate ) and the cation part which consists of a racemic octahedrally coordinated zinc center defined six nitrogen atoms from three phen rings to form an inorganic chirality that can be resolution by chiral organic ligand, the 3D framework was formed through the strong H-bonding interaction between sulfonate and water. CCDC: 277924.     

Reactions of 1-aryl- and 2,3-diaryl- 5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetra- hydroindazoles with N-ethyl- and N-phenyl-substituted maleimides

[3+2] Cyclocondensation reactions of a series of 1,3- and 2,3-disubstituted 5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles with N-ethyl- and N-phenyl-substituted maleimides have been used to obtain the corresponding 6,6-dimethyl-4,4',6'-trioxo-4,5,6,7-3',3'a,4',5',6',6'a-decahydrospiro-[indazole-5,3'-pyrrolo[3,4-c]pyrazoles]. On boiling these compounds in toluene nitrogen is split off and they are converted into 6',6'-dimethyl-2,4,4'-trioxo-4',5',6',7'-tetrahydro-1'H-spiro[3-azabicyclo-(3.1.0)hexane-6,5'-indazoles].     

NMR and quantum chemical study on the OH...pi and CH...O interactions between trehalose and unsaturated fatty acids: implication for the mechanism of antioxidant function of trehalose

Trehalose is a disaccharide that attracts much attention as a stress protectant. In this study, we investigated the mechanism of the antioxidant function of trehalose. The spin-lattice relaxation times (T(1)) of (1)H and (13)C NMR spectra were measured to investigate the interaction between trehalose and unsaturated fatty acid (UFA). We selected several kinds of UFA that differ in the number of double bonds and in their configurations (cis or trans). Several other disaccharides (sucrose, maltose, neotrehalose, maltitol, and sorbitol) were also analyzed by NMR. The T(1) values for the (1)H and (13)C signals assigned to the olefin double bonds in UFA decrease with increasing concentration of trehalose and the changes reaches plateaus at integer ratios of trehalose to UFA. The characteristic T(1) change is observed only for the combination of trehalose and UFA with cis double bond(s). On the other hand, from the (13)C-T(1) measurements for trehalose, the T(1) values of the C-3 (C-3') and C-6' (C-6) are found to change remarkably by addition of UFA. (1)H[bond](1)H NOESY measurements provide direct evidence for complexation of trehalose with linoleic acid. These results indicate that one trehalose molecule stoichiometrically interacts with one cis-olefin double bond of UFA. Computer modeling study indicates that trehalose forms a stable complex with an olefin double bond through OH...pi and CH...O types of hydrogen bonding. Furthermore, a significant increase in the activation energy is found for hydrogen abstraction reaction from the methylene group located between the double bonds that are both interacting with the trehalose molecules. Therefore, trehalose has a significant depression effect on the oxidation of UFA through the weak interaction with the double bond(s). This is the first study to elucidate the antioxidant function of trehalose.