Corrole and nucleophilic aromatic substitution are not incompatible: a novel route to 2,3-difunctionalized copper corrolates.

The insertion of a -NO2 group onto the corrole framework represents a key step for subsequent synthetic manipulation of the macrocycle based on the chemical versatility of such a functionality. Here we report results of the investigation of a copper 3-NO2-triarylcorrolate in nucleophilic aromatic substitution reactions with "active" methylene carbanions, namely diethyl malonate and diethyl 2-chloromalonate. Although similar reactions on nitroporphyrins afford chlorin derivatives, nucleophilic attack on carbon-2 of corrole produces 2,3-difunctionalized Cu corrolates in acceptable yields (ca. 30%), evidencing once again the erratic chemistry of this contracted porphyrinoid.

3-NO2-5,10,15-triarylcorrolato-Cu as a versatile platform for synthesis of novel 3-functionalized corrole derivatives.

ß-Nitrocorroles are potentially valuable platforms for the preparation of a wide range of more elaborated corrole derivatives possessing unique chemical functionalities and electronic properties. Here we report our results on the chemical manipulation of a copper 3-NO2-triarylcorrolate using different organic reactions, all involving the reduction of -NO2 to -NH2 at an early stage, followed by further transformations. By way of a ß-acylated copper corrolate, a novel corrole derivative bearing an alkyl azide group on the peripheral positions was obtained and exploited in the Huisgen 1,3-dipolar cycloaddition.

Geometries and conformational processes in phencyclidine and a rigid adamantyl analogue: variable-temperature NMR, X-ray crystallographic, and molecular mechanics studies.

The barriers to rotation of the aryl groups of m-nitrophenyladamantylpiperidine and m-nitrophenylcyclohexylpiperidine have been studied by variable-temperature NMR spectroscopy. NMR spectra of the free bases and salts of phenyladamantylpiperidine and phenylcyclohexylpiperidine (phencyclidine) and an X-ray crystal structure of the adamantane derivative verify the preferred conformations of these molecules in solution and the solid state. Force-field calculations provide additional information on the energetics of conformational processes in these molecules.

(+)-Hemipalmitoylcarnitinium strongly inhibits carnitine palmitoyltransferase-I in intact mitochondria.

The reaction of the methyl ester of (R)-norcarnitine with 1-bromo-2-heptadecanone produces (+)-6-[(methoxycarbonyl)methyl]-2-pentadecyl-4,4-dimethylmorpholinium bromide, 3, which hydrolyzes to (+)-6-(carboxylatomethyl)-2-pentadecyl-4,4-dimethylmorpholinium (hemipalmitoylcarnitinium, HPC) upon treatment with aqueous sodium hydroxide. Single-crystal X-ray analyses have confirmed the structures of (+)-HPC and 3. (+)-HPC inhibits carnitine palmitoyltransferase (CPT-I) activity for the forward reaction (palmitoyl-CoA + carnitine-->) in intact mitochondria from rat heart and rat liver. (+)-HPC competitively (versus carnitine) inhibits CPT-I activity in both rat heart and liver mitochondria with Ki = 2.8 +/- 0.5 and 4.2 +/- 0.7 microM, respectively. As one of the strongest specific inhibitors of CPT-I, HPC is a potential therapeutic agent in myocardial ischemia and Type II diabetes.

Solid-state supramolecular structures of resorcinol-arylboronic acid compounds.

[structure: see text] An X-ray crystallographic study of unique hydrogen-bonded supramolecular solid-state networks comprised of a tetraarylboronic acid resorcinarene is described. When 1 is recrystallized from 9:1 MeOH:EtOH, partial esterification takes place to give compound 2, the corresponding half methyl ester, which forms an infinite two-dimensional array. Each molecule participates in 12 hydrogen bonds with other macrocycles. These hydrogen bonds are both B-OH- - - OH (phenolic) and OH (phenolic)- - -OH (phenolic).

Synthesis of a reaction intermediate analogue of biotin-dependent carboxylases via a selective derivatization of biotin.

[formula: see text] An efficient and practical synthesis of 1, a unique reaction intermediate analogue of biotin-dependent carboxylases, is described. The synthesis features a selective acylation of the 1'-N of biotin. Target 1 inhibits the activity of the biotin carboxylase component of acetyl CoA carboxylase. It is the first known biotin-derived inhibitor of biotin carboxylase and should promote new kinetic and structural studies of the biotin-dependent carboxylases.

A new cryptand: synthesis and complexation with paraquat.

[formula: see text] Inspired by folded, nonpseudorotaxane complexes of bis(m-phenylene)-32-crown-10 systems, we synthesized a new bicyclic crown ether containing two 1,3,5-phenylene units linked by three tetra(ethyleneoxy) units. The new cryptand forms a "pseudorotaxane-like" inclusion complex with N,N'-dimethyl-4,4'-bipyridinium bis(hexafluorophosphate) with association constant Ka = 6.1 x 10(4) M-1, 100-fold greater than that of an analogous simple crown ether.

Dibenzocyclooctadiene-type lignans from Magnolia pyramidata.

Eight dibenzocyclooctadiene-type lignans, pyramidatin A-H, were isolated from the leaves of Magnolia pyramidata. Their structures were established by spectral methods, mainly 2D NMR spectroscopic techniques, which involved combined applications of COSY, DEPT. 1H, 13C correlations, COLOC, INAPT and long-range inverse 1H, 13C NMR correlations. The molecular structures of pyramidatin A and B were determined by single crystal X-ray diffraction. The absolute configurations of all eight lignans were derived from CD spectral correlations with structurally related dibenzocyclooctadienes of known absolute configuration.

Cyanoglucosides from Osmaronia cerasiformis (Rosaceae).

Three nitrile glucosides have been isolated from a methanolic extract of the leaves of Osmaronia cerasiformis (Torr. & Gray) Greene (Rosaceae, Prunoideae). One is the known sutherlandin (Z-4-beta-D-glucopyranosyloxy-3-hydroxymethylbut-2-ene nitrile); the second is Z-4-beta-glucopyranosyloxy-3-methylbut-2-ene nitrile, which has recently been characterized but whose stereochemistry was not previously determined; the Z-isomer identified here was named osmaronin. The third is the new 4-beta-D-glucopyranosyloxy-2R,3R-epoxy-3-methylbutyronitrile (osmaronin epoxide). The nitrile glucosides occur in the leaves and flowers of the title plant; their aglycone is apparently derived from the aliphatic amino acid L-leucine.

Synthesis and X-ray crystal and solution structures of 2,5-anhydro-3,4-O-(1,2-ethanediyl)-D-mannitol: a locked 4T3 furanose conformer.

2,5-Anhydro-3,4-O-(1,2-ethanediyl)-D-mannitol (1) was prepared from 2,5-anhydro-D-mannitol (2) in three steps. The fused ring system was introduced by a phase-transfer alkylation using 1,2-dibromoethane. Its conformation in solution was determined by NMR studies at 500 MHz. Variable-temperature studies showed no lineshape change from 25 to 80 degrees in D2O. The data indicate that the five-membered ring is locked by the trans-fused six-membered 1,4-dioxane ring into a twist 4T3 conformation. A single-crystal X-ray study was carried out. The crystals are orthorhombic, C222(1), a = 4.7252 (6), b = 14.0364 (12), c = 13.268 (2) A, Z = 4, with R = 0.032 for 894 observations. The molecule lies upon a crystallographic two-fold axis, and thus the five-membered ring exists in a perfect 4T3 conformation with a pseudorotation angle of 0 degree and amplitude of 47.2 degrees, in agreement with the NMR results. We have shown earlier that, among twenty possible conformers, phosphofructokinase acts specifically on the 4T3 conformer of the beta anomer of D-fructose 6-phosphate.

Conformations and structure studies of sugar lactones. Part III. The composition and conformation of D-mannurono-gamma-lactone in solution, and the structural analysis of its beta anomer in the solid state.

Complete analyses of the proton and carbon chemical-shift assignments of D-mannurono-gamma-lactone (1) have been achieved by 1D and 2D NMR spectral measurements. At equilibrium, the anomeric alpha and beta forms were present in the ratio of 34:66 in D2O and 72:28 in Me2SO-d6. The solution data indicated that the dienvelope conformation 2E:E4 to be the favored conformation of 1 in solution. The crystal structure of 1 was determined, and it showed that the crystalline form is the beta anomer, a bicyclic structure, consisting of fused five-membered furanose and lactone rings, in agreement with an earlier deduction from chemical evidence. In contrast to the solution conformation, the furanose ring adopts a twist conformation lying between the 2(1)T and 1E conformations with phase angle (P) and pseudorotation amplitude (tau m) of -44.23 degrees and 37.9 degrees, respectively, whereas the lactone ring adopts an envelope E5 conformation slightly distorted towards 6T5 with a phase angle (P) of -22.3 degrees and a pseudorotation amplitude (tau m) of 18.4 degrees. The molecules are linked in the crystal through a hydrogen-bonding network that involves all hydroxyl groups as well as the ring oxygen atoms.

The configuration and conformation of di-D-fructose anhydride I. The crystal and molecular structure of 3,4,3',4'-tetra-O-acetyl-6,6'-di (triphenylmethyl)-di-D-fructose anhydride I.

The crystal structure of 3,4,3',4'-tetra-O-acetyl- 6,6'-di(triphenylmethyl)-di-D-fructose anhydride I (1) has been determined by single-crystal X-ray diffraction. The crystals are monoclinic, space group P2(1) with a = 16.399(2), b = 9.091(2), c = 17.946(4) A, beta = 103.66(1) degrees, V = 2600(2) A3, and Z = 2. The structure was refined to R = 0.044 and Rw = 0.051 for 4403 observed reflections. The structure analysis of 1 showed that the previously assigned chemical structure of di-D-fructose anhydride I is undoubtedly alpha-D-fructofuranose beta-D-fructofuranose 1,2':2,1'-dianhydride. The conformations of the furanose rings are E5 with P = 59.8 and tau m = 43.2 degrees for D-fructose 1, and 2T3 with P = -34.39 degrees and tau m = 39.64 degrees for D-fructose 2. The two furanose fragments are linked by a 1,4-dioxane ring in a spiro arrangement. The 1,4-dioxane ring has a chair conformation with Cremer-Pople puckering parameters Q = 0.527 A, phi = 72.2 degrees and the a = 14.2 degrees.

The crystal and molecular structure of 1,2-O-isopropylidene-alpha-D-xylo-pentodialdo-1,4-furanose. A dimeric form in the crystalline state.

1,2-O-isopropylidene-alpha-D-xylo-pentodialdo-1,4-furanose (1), C16H24O10, M(r) = 376.4, is orthorhombic, space group P2(1)2(1)2(1) with a = 10.3028(10), b = 11.1875(3), c = 15.7484(13) A, V = 1815.2(4) A3, Dc = 1.377 gcm-3, mu(CuK alpha) = 9.5 cm-1 and Z = 4. The structure was refined to R = 0.033 and Rw = 0.045 for 1984 observed reflections. Crystalline 1 has a dimeric cyclic acetal-hemiacetal structure, formed by self aldol condensation of two monomers. The absolute configuration at the condensation centers, C-5 and C-5', were assigned as 5R and 5S, respectively. In the dimer 1, the xylofuranose rings adopt different conformations, one is a twist 3T4, whereas the second is an envelope E4 slightly distorted towards the 3T4 conformation; their fused 1,2-O-isopropylidene rings adopt O-2E and O-2TC-6 conformations, respectively. The 1,3-dioxane ring has a distorted chair conformation with puckering parameters Q = 0.516 A, phi = 90.9, and theta = 11.0 degrees. The molecules are linked in the crystal through intermolecular hydrogen-bonding interactions that involve the two hydroxyl groups, OH-3 and OH-5', and the isopropylidene ring oxygen atoms, O-2 and O-1', as donor and acceptor, respectively.

Conformational features of rhamnopyranose derivatives. The molecular structure of methyl 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranoside.

Methyl 2,3,4-tri-O-acetyl-alpha-L-rhamnopyranoside, C13H20O8, M(r) = 304.3, is monoclinic, space group C2, with a = 23.619(1), b = 8.2168(5), c = 19.093(1) A, beta = 118.72(1) degrees, V = 3249.6(8) A3, Dc = 1.244 g cm-3, mu (MoK alpha) = 0.97 cm-1 and Z = 8. The structure was refined to R = 0.044 and Rw = 0.039 for 1969 observed reflections. There are two independent molecules in the asymmetric unit. The bond lengths and bond angles of the pyranose rings of the two are in good agreement within the limits of error. The molecules have similar conformation except for the orientation of one of the acetoxy groups. Each molecule is a normal 1C4 chair with Cremer-Pople puckering parameters Q = 0.557(6) A, theta = 174.6(2) degrees and psi = 144.6(9) degrees for molecule A and 0.564(4) A, 177.9(1) degree and 30.8(8) degrees for molecule B, respectively. The acetyl groups have the planar, (S)-cis conformation most commonly observed. They are oriented with the acetyl planes within +/- 35 degrees of the C-H bond at the ring carbon atom to which they are attached.

Conformations and structure studies of sugar lactones in the solid state. Part I. The molecular structure of L-rhamnono- and L-mannono-1,4-lactones.

The crystal structures of L-rhamnono-1,4-lactone (1) and L-mannono-1,4-lactone (2) have been determined by single-crystal X-ray diffraction. Pertinent crystal data are as follows: for 1, orthorhombic, space group P2(1)2(1)2(1), a = 4.8829(2), b = 10.9088(8), c = 13.9758(9) A, V = 734.7(1) A3, Dc = 1.610 g cm-3, Z = 4, R = 0.028 and Rw = 0.035 for 1586 reflections. The lactone ring of 1 adopts an envelope conformation, E3, slightly distorted toward 2T3, with psi = 103.1(7) degrees and q = 0.38(3) A, whereas the lactone ring of 2 adopts a perfect envelope E3 conformation, with psi = 106.6(4) degrees and q = 0.42(4) A. Molecules of 1 and 2 are linked in their crystals through a three dimensional network of O-H ... H hydrogen-bonding interactions that involves all hydroxyl groups as well as the carbonyl oxygen atom.

Synthesis of 3,4-di-O-acetyl-2,5-anhydro-1,6-dideoxy-1,6-diiodo-D-mannitol. Comparison of NMR spectral results for the solid state and solution with those of the X-ray structural determination.

3,4-Di-O-acetyl-2,5-anhydro-1,6-dideoxy-1,6-diiodo-D-mannitol (3) is prepared from 2,5-anhydro-D-mannitol (1) in three steps. The solution and solid-state NMR spectra of 3 indicate considerable variation in conformation. In solution, it adopts, on average, a symmetric 4T3 conformation, whereas in the solid state it adopts an asymmetric conformation as revealed by 13C NMR cross polarization and magic angle spinning techniques. A single-crystal X-ray structure analysis confirmed the asymmetric conformation of 3 in a monoclinic crystal, space group P2(1) with a = 8.9608(4), b = 8.6348(5), c = 9.6468(4) A, beta = 96.139(4) degrees, V = 742.1(1) A3, Dc = 2.085 g cm-3, mu (MoK alpha) = 4.2 mm-1, and Z = 2. The structure was refined to R = 0.039 and Rw = 0.047 for 5181 observed reflections. The furanoid ring of 3 adopts an envelope E5 conformation slightly distorted towards 4T5, with puckering parameters psi = 313.49 degrees and q = 0.37 A. The asymmetric conformation is rationalized in terms of the weak packing forces in the crystal.

The X-ray crystal structure of 2,3:4,5-di-O-isopropylidene-1-O-methyl-beta-D-fructopyranose.

2,3:4,5-Di-O-isopropylidene-1-O-methyl-beta-D-fructopyranose, C13H22O6, Mr = 274.3, orthorhombic, P212121, a = 12.388 (2), b = 13.307 (5), c = 8.660 (1) A, V = 1427.4 (9) A3, Z = 4, Dm = 1.24 g.cm-3, Dx = 1.276 g.cm-3, CuKalpha, lambda = 1.54184 A, mu = 8.0 cm-1, F(000) = 592, T = 295 (1) K, R = 0.032 for 1586 observations (of 1693 unique data). The molecule is a derivative of the naturally occurring carbohydrate D-fructose. The data reported here indicate that the ketose six-membered ring is constrained by the presence of two fused five-membered rings into the 3SO conformation. These findings agree with the n.m.r.-spectroscopic results for 2,3:4,5-di-O-benzylidene-beta-D-fructopyranose. As a result of crystal packing forces, the exocyclic side-chain has a C-C-O-C torsion angle of -102 degrees, quite different from the expected value of 180 degrees.

Crystal structure of 2,5-anhydro-1-O-(p-tolylsulfonyl)-D-mannitol.

2,5-Anhydro-1-O-(p-tolylsulfonyl)-D-mannitol, C13H18SO7, Mr = 318.4, monoclinic, C2, a = 26.370(6), b = 7.9741(11), c = 6.6801(6) A, beta = 91.401(11) degrees, V = 1404.3(6) A3, Z = 4, DX = 1.506 g/cm3, CuK alpha, lambda = 1.54184 A, mu = 23.03 cm-1, F(000) = 672, T = 296(1) K, R = 0.042 for 2832 observations with I > 3 sigma (I) (of 2864 unique data). On the esterified side of the molecule, three bond lengths and three bond angles show small changes compared to the unesterified side, which is similar to the symmetrical parent compound, 2,5-anhydro-D-mannitol. The conformation of the five-membered ring is E5 with P = 49.3 degrees and tau m = 38.1 degrees. The hydroxymethyl groups adopt g+ and g- dispositions similar to the parent molecule. The three hydroxyl groups are involved in a network of intermolecular hydrogen bounds both as donors and acceptors.

Conformations and structure studies of sugar lactones in the solid state. Part II. The molecular structure of alpha-D-glucosaccharino-gamma-lactone: 2-C-methyl-D-ribo-pentono-1,4-lactone.

The crystal structure of 2-C-methyl-D-ribo-pentono-1,4-lactone (alpha-D-glucosaccharino-gamma-lactone, 1) has been determined by single-crystal X-ray diffraction. The crystals are orthorhombic, space group P2(1)2(1)2(1) with a = 7.7429(6), b = 8.3373(7), c = 11.3258(7) A, V = 731.1(2) A3 (CuK alpha, lambda = 1.54184 A), mu = 10.82 cm-1, Dc = 1.473 g cm-3, and Z = 4. The structure was refined to R = 0.0307 and Rw = 0.0424 for 876 observed reflections. Compound 1 has the D-ribo configuration, in agreement with an earlier deduction from chemical evidence. The lactone ring adopts the 3T2 conformation, with puckering parameters psi = 279.8(9) degrees and q = 0.32(5) A. The orientation of the methyl group about the C-2-C-3 bond is gauche-trans, with the C-6-C-2-C-3-O-3 and C-6-C-2-C-3-C-4 torsion angles being -81.3(2) degrees and 154.7(1) degree, respectively. The molecules are linked in the crystal in a two-dimensional intermolecular hydrogen bonding network that involves all hydroxyl groups as well as the carbonyl oxygen atom.

Synthesis of novel carboranylchlorins with dual application in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT).

Total synthesis of carboranylchlorins 3 and 4, from readily available starting materials, are described and the molecular structures of two key intermediates are presented. Chlorins 3 and 4 show similar spectroscopic behavior but differ considerably in their solubility properties; whereas closo-carboranylchlorin 3 is completely insoluble in water, its nido derivative 4 has good water-solubility. Carboranylchlorin 3 absorbs in the red region of the optical spectrum (at lambda(max)=642 nm) six times more strongly than porphyrin 1, and displays a fluorescence emission band at lambda(max)=651 nm, upon excitation at 642 nm. The water-soluble carboranylchlorin 4 also displays intense absorption and emission bands at lambda(max)=642 and 651 nm, respectively, in ethanol solution. It is concluded that carboranylchlorins 3 and 4 have higher promise for the dual application in PDT and BNCT than do comparable porphyrins.