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.

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.

Space-group revision for 4-formylphenylboronic acid.

The space group of the title compound, C7H7BO3, previously reported to be P1, is properly Cc. There is no disorder of the formyl group or in the H atoms of the B(OH)2 group. Molecules lie on approximate twofold axes and are related by approximate centers, which relate all but the formyl O atom and boronic acid H atoms. The B-O distances are 1.363 (2) and 1.370 (2) A.

Sterically hindered C(alpha, alpha)-disubstituted alpha-amino acids: synthesis from alpha-nitroacetate and incorporation into peptides.

The preparation of sterically hindered and polyfunctional C(alpha,alpha)-disubstituted alpha-amino acids (alpha alpha AAs) via alkylation of ethyl nitroacetate and transformation into derivatives ready for incorporation into peptides are described. Treatment of ethyl nitroacetate with N,N-diisopropylethylamine (DIEA) in the presence of a catalytic amount of tetraalkylammonium salt, followed by the addition of an activated alkyl halide or Michael acceptor, gives the doubly C-alkylated product in good to excellent yields. Selective nitro reduction with Zn in acetic acid or hydrogen over Raney Ni gives the corresponding amino ester that, upon saponification, can be protected with the fluorenylmethyloxycarbonyl (Fmoc) group. The first synthesis of an orthogonally protected, tetrafunctional C(alpha,alpha)-disubstituted analogue of aspartic acid, 2,2-bis(tert-butylcarboxymethyl)glycine (Bcmg), is described. Also, the sterically demanding C(alpha,alpha)-dibenzylglycine (Dbg) has been incorporated into a peptide using solid-phase synthesis. It was found that once sterically congested Dbg is at the peptide N-terminus, further chain extension becomes very difficult using uronium or phosphonium salts (PyAOP, PyAOP/HOAt, HATU). However, preformed amino acid symmetrical anhydride couples to N-terminal Dbg in almost quantitative yield in nonpolar solvent (dichloroethane-DMF, 9:1).

Separating the racemic and meso diastereomers of a binucleating tetraphosphine ligand system through the use of nickel chloride.

The reaction of a 1:1 mixture of rac- and meso-et,ph-P4 (et,ph-P4 = (Et(2)PCH(2)CH(2))(Ph)PCH(2)P(Ph)CH(2)CH(2)PEt(2)) with 2 equiv of NiCl(2).6H(2)O in EtOH produces soluble rac-Ni(2)Cl(4)(et,ph-P4) and precipitates meso-Ni(2)Cl(4)(et,ph-P4), allowing facile isolation of each bimetallic complex. Subsequent reaction with more than 250 equiv of NaCN in H(2)O/MeOH releases the et,ph-P4 ligand and [Ni(CN)(4)](2-). The rac,trans- and meso,trans-Ni(CN)(2)(eta(2.5)-et,ph-P4) form as intermediates in the cyanolysis of rac- and meso-Ni(2)Cl(4)(et,ph-P4). These have been characterized by X-ray crystallography. The unusual partial isomerization of the meso- to rac-et,ph-P4 ligand via the monometallic trans-Ni(CN)(2)(eta(2.5)-et,ph-P4) intermediate complex is discussed.

A monometallic Rh(III) tetraphosphine complex: reductive activation of CH2Cl2 and selective meso to racemic tetraphosphine ligand isomerization.

The first Rh complex with an eta(4)-coordinated rac-et,ph-P4 ligand [et,ph-P4 = (Et2PCH2CH2)(Ph)PCH2P(Ph)(CH2CH2PEt2)] has been synthesized by reacting [Rh(nbd)2]BF4 with meso- or rac-et,ph-P4 in dichloromethane. The reaction occurs fairly rapidly at room temperature to form [rac-RhCl2(eta(4)-et,ph-P4)](+) in high yields, regardless of whether one starts with mixed or even pure meso-et,ph-P4 ligand. This unusual and highly selective metal assisted isomerization of the meso-et,ph-P4 ligand to its rac-et,ph-P4 disastereomer will be discussed.

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).

2,5-O-methylene-D-mannitol: two polymorphs and the NaI complex.

Two polymorphs of the title compound, (4R,5R,6R,7R)-4,7-bis(hydroxymethyl)-1,3-dioxepane-5,6-diol, C(7)H(14)O(6), both have Z' = 2 at 100 K, and differ in their hydrogen-bonding patterns. The sodium iodide complex, NaI.C(7)H(14)O(6), is isomorphous with the NaCl complex, and has the mannitol, cation and anion all lying on twofold axes. The dioxepane rings of all three molecules are in the twist-chair conformation.

Two stereoisomeric pentacyclic oxindole alkaloids from Uncaria tomentosa: uncarine C and uncarine E.

The chloroform solvate of uncarine C (pteropodine), (1'S,3R,4'aS,5'aS,10'aS)-1,2,5',5'a,7',8',10',10'a-octahydro-1'-methyl-2-oxospiro[3H-indole-3,6'(4'aH)-[1H]pyrano[3,4-f]indolizine]-4'-carboxylic acid methyl ester, C(21)H(24)N(2)O(4).CHCl(3), has an absolute configuration with the spiro C atom in the R configuration. Its epimer at the spiro C atom, uncarine E (isopteropodine), (1'S,3S,4'aS,5'aS,10'aS)-1,2,5',5'a,7',8',10',10'a-octahydro-1'-methyl-2-oxospiro[3H-indole-3,6'(4'aH)-[1H]pyrano[3,4-f]indolizine]-4'-carboxylic acid methyl ester, C(21)H(24)N(2)O(4), has Z' = 3, with no solvent. Both form intermolecular hydrogen bonds involving only the oxindole, with N.O distances in the range 2.759 (4)-2.894 (5) A.

New allo-cedrane type sesquiterpene hemiketals and further sesquiterpene lactones from fruits of Illicium floridanum.

Three new tetracyclic sesquiterpene hemiketals possessing the very rare allo-cedrane carbon skeleton, debenzoyl-7-deoxo-1 alpha,7 alpha-dihydroxytashironin, debenzoyl-7-deoxo-7 alpha-hydroxytashironin, and debenzoyl-7-deoxo-7 alpha-hydroxy-3-oxotashironin (1--3), were isolated from the fruits of Illicium floridanum ELLIS (American Star Anise, Star bush). Their structures were elucidated by mass and NMR spectroscopic analyses. The molecular structure of 1, including absolute stereochemistry, was determined by single-crystal X-ray diffraction of its monohydrate. Only one compound of this type, tashironin, has previously been isolated from Illicium tashiroi. Furthermore, a new sesquiterpene lactone of the seco-prezizaane type, 3,4-anhydro-13,14-dihydroxyfloridanolide (4), and the known anislactone B (5) were isolated. The occurrence of further allo-cedrane sesquiterpenes in another Illicium species confirms the hypothesis of previous authors that this type of compound is a biogenetic precursor of the typical seco-prezizaane sesquiterpene lactones found in this genus. Moreover, regarding their co-occurrence with anislactone B as reported here, they may also be considered precursors for the anislactone skeletal type.

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.

Two N-ortho-nitrobenzenesulfonyl alpha,alpha-disubstituted amino acid adducts.

The carboxy group of 2-methyl-N-[(2-nitrophenyl)sulfonyl]alanine, C(10)H(12)N(2)O(6)S, forms centrosymmetric hydrogen-bonded dimers with an O.O distance of 2.629 (2) A and an intramolecular N-H. O(nitro) hydrogen bond N.O distance of 2.823 (2) A. 1-[(2-Nitrophenyl)sulfonylamino]cyclohexanecarboxylic acid, C(13)H(16)N(2)O(6)S, has Z' = 2 and forms similar interactions.

Tetrakis(diethylamino)phosphonium bromide hemihydrate.

The structure of the title compound, C(16)H(40)N(4)P(+).Br(-).0. 5H(2)O or [P¿N(C(2)H(5))(2)¿(4)]Br.0.5H(2)O, at 130 K has Z' = 4 and is ionic, with Br not bonded to P. The P atoms are tetrahedral, with P-N distances in the range 1.628 (2)-1.6400 (19) A. The N atoms are approximately planar. The water molecules form cyclic hydrogen-bonded [(H(2)O)(2)Br(2)](2-) units about inversion centers, with O.Br distances in the range 3.425 (2)-3.611 (3) A.

GR 24 enantiomers: synthesis, NMR spectroscopy, X-ray crystallography, and separation by chiral electrokinetic capillary chromatography.

Chiral discrimination of enantiomers of 2-methyl-4-(2-oxo-2,3,3a,8b-tetrahydro-4H-indeno[1,2b]furan-3-yl-iden emethoxy)but-2-en-4-olide (commonly referred to as GR 24) by three polymeric chiral surfactants (PCS) is studied by use of chiral polymeric surfactant capillary electrophoresis (CPSCE). The CPSCE results indicate that the optical configurations of valine residues on the PCS backbone affect chiral resolution and elution order of GR24 stereoisomers. The L- and D-forms of poly(sodium N-undecanoyl valinate) provide baseline separation of all four enantiomers while the DL-form separates diastereomers of GR 24 (1). A model is presented rationalizing the migration behavior and chiral resolution of 1 in CPSCE. The actual configuration of the stereogenic centers of GR 24 and 3-[(2,5-dihydro-3-methyl-2-oxo-5-furanyl)oxo]-methylene-3,3a,6,6a-tetrah ydro-2H-cyclopenta[b]furan-2-one (GR 7) is established by a concerted application of high-resolution nuclear magnetic resonance spectroscopy and X-ray crystallography.

A chiral furocoumarin.

The furocoumarin 1,2-dihydro-2-(1,2-dihydroxyprop-2-yl)-8H-furo[2,3-h]benzopyran-8-one crystallizes from methanol-water as the monohydrate C(14)H(14)O(5).H(2)O. Both chiral centers have the S configuration. Both OH groups and both H atoms of the water molecule form intermolecular hydrogen bonds with O.O distances in the range 2.7686 (18)-2.8717 (18) A.

Selective tin-carbon bond cleavage reactions of trimethylstannylzirconocene dichloride with electrophiles.

The reaction of 5,5-bis(trimethylstannyl)cyclopentadiene with CpZrCl3 (Cp = eta 5-C5H5) affords the monostannylated metallocene complex (eta 5-Me3SnC5H4)CpZrCl2 (1), accompanied by variable amounts of (eta 5-ClMe2SnC5H4)CpZrCl2 (2). The complex (1) reacts with BCl3 or with ICl to afford 2 (Sn-CH3 cleavage), but with HCl, Cp2ZrCl2 is obtained instead (Sn-Cp cleavage). Depending on the reaction conditions, treatment of either 1 or 2 with BBr3 affords (eta 5-BrMe2SnC5H4)CpZrBr2 (3) or (eta 5-Br2MeSnC5H4)CpZrBr2 (4). The reaction of 1 with excess I2 affords the iodostannylated complex (eta 5-IMe2SnC5H4)CpZrCl2 (5). Two of the complexes (2.2C6H5CH3 and 4.THF) are crystallographically characterized. The adduct 4.THF has a distorted trigonal bipyramidal geometry about tin with a long O-Sn distance of 2.655 A. We find overall that Me3Sn substituents undergo electrophilic halodemethylation much more readily than corresponding Me3Si substituents, whereas the reactivities of the halostannylated complexes toward nucleophiles such as airborne moisture are much lower than those of their halosilylated counterparts.

Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia subtomentosa.

In a bioassay guided search for antimycobacterial compounds from higher plants, the root extracts of Elecampane (Inula helenium L.; Asteraceae) and Sweet Coneflower (Rudbeckia subtomentosa Pursh.; Asteraceae) were chemically investigated for their active constituents. Chromatographic fractions of root extracts of l. helenium, which exhibited significant activity against Mycobacterium tuberculosis, provided the known eudesmanolides alantolactone, isoalantolactone, and 11 alpha H, 13-dihydroisoalantolactone. Peracid epoxidation of alantolactone and isoalantolactone provided 5 alpha-epoxyalantolactone and 4(15) alpha-epoxyisoalantolactone, respectively and oxidation of alantolactone with OsO4 gave 11,13-dihydroxyalantolactone. Active fractions from R subtomentosa contained the known alloalantolactone and 3-oxoalloalantolactone. The structures of the above compounds were established by spectroscopic methods including 1D and 2D NMR techniques as well as spectral comparison with previously reported data. The molecular structure of 5 alpha-epoxyalantolactone was determined by single crystal X-ray diffraction. Eleven natural and semisynthetic eudesmanolides were tested in a radiorespirometric bioassay for activity against M. tuberculosis. 5 alpha-Epoxyalantolactone and encelin from Montanoa speciosa showed minimum inhibitory concentrations (MICs) of 8 and 16 micrograms ml-1, respectively. Alantolactone, isoalantolactone and its 4 alpha, 15-epoxide, 1,2-dehydro-3-epi-isotelekin and alloalantolactone gave MICs of 32 micrograms ml-1. All other compounds showed MIC values of 128 micrograms ml-1 or higher.

Antimycobacterial ergosterol-5,8-endoperoxide from Ajuga remota.

In a bioassay-guided search for antimycobacterial natural products from higher plants, we have chemically investigated the methanol extract of aerial parts of Ajuga remota Benth. (Labiatae) for its active constituent(s). Bioactive chromatographic fractions of the crude extract provided the known triterpene ergosterol-5,8-endoperoxide plus the diterpenes clerodin, ajugarin-I, and ajugarin-II, which had been previously isolated from A. remota. This is the first report on the isolation of ergosterol-5,8-endoperoxide from this plant. The above compounds were tested in a radiorespirometric bioassay for activity against Mycobacterium tuberculosis. Ergosterol-5,8-endoperoxide showed a minimum inhibitory concentration (MIC) of 1 microgram/ml, while ergosterol-5,8-endoperoxide acetate, ergosterol, and ergosta-5,7,9(11),22-tetraen-3 beta-ol gave MICs of 8 micrograms/ml, > 128 micrograms/ml, and 128 micrograms/ml, respectively. Clerodin, ajugarin-I, and ajugarin-II were inactive with MICs of > 128 micrograms/ml.