Ring Bridge Research Articles

Novel diterpene lactones from Suregada multiflora.

Two new diterpene lactones, suregadolides A (1) and B (2), were isolated from a dichloromethane extract of Suregada multiflora bark. These compounds possess a novel skeleton, which contains a cyclopropane ring bridging C-3 and C-4 of the abietane skeleton. The structures were established on the basis of one- and two-dimensional NMR and other spectroscopic studies. Compound 1 showed moderate inhibitory activity in a mutant yeast strain bioassay.

Ring Flexibility within Tricyclic Antidepressant Drugs

The internal flexibility of the central seven‐membered ring of a series of tricyclic antidepressant drugs (TCAs), imipramine {1}, amitriptyline {2}, doxepin {3}, and dothiepin {4}, has been investigated by 1H and 13C nuclear magnetic (NMR) techniques. Two dynamic processes were examined: ring inversion and bridge flexing. 1H NMR line‐shape analysis was used to obtain ring inversion barriers for 2–4. These studies yielded energy barriers of 14.3, 16.7, and 15.7 ± 0.6 kcal/mol for the hydrochloride salts of doxepin, dothiepin, and amitriptyline, respectively. The barriers for the corresponding free bases were lower by 0.6 kcal/mol on average. 13C T1 relaxation measurements were used to determine the degree of bridge flexing associated with the central seven‐membered ring for all four compounds. By fitting the T1 data to a two‐state jump model, lifetimes and amplitudes of rapid bridge flexing motions were determined. The results show that imipramine has the fastest rate of bridge flexing, followed by amitriptyline, doxepin, and dothiepin. The pharmacological profiles of the TCAs are complex and they interact with many receptor sites, resulting in numerous side effects and a general lack of understanding of their precise mode of action in different anxiety‐related disorders. They all have similar three‐dimensional structures, which makes it difficult to rationalize their differing relative potency in different assays/clinical settings. However, the clear finding here that there are significantly different degrees of internal mobility suggests that molecular dynamics should be an additional factor considered when trying to understand the mode of action of this clinically important family of molecules. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:713–721, 2001

Dihydroparthenolide diol, a novel sesquiterpene lactone

The title compound, 2,10-di­hydroxy-1,6,10-tri­methyl-4,14-dioxatri­cyclo­[9.2.1.03,7]­tetradecan-5-one, C15H24O5, a novel sesquiterpene lactone synthesized from di­hydro­parthenolide, has a 1,4-furano bridge in the 10-membered ring and a trans-fused α-methyl-γ-lactone.

Novel cationic and neutral Pd(II) complexes bearing imidazole based chelate ligands: synthesis, structural characterisation and catalytic behaviour

A variety of neutral and cationic methyl palladium(II) complexes [Pd(CH 3)(Cl)(L–L)] ( 3) and [Pd(CH 3)(CH 3CN)(L–L)]BF 4 ( 4), containing known and new N-methylimidazole-2-yl (mim) and N-methylbenzimidazole-2-yl (bmim) based chelate ligands (L–L) have been synthesised. The dichloro complexes [Pd(Cl) 2{(mim) 2CO}] ( 2b) and [Pd(Cl) 2(mim)PPh 2] ( 2e) have also been synthesised. The crystal structures of [Pd(Cl) 2{(mim) 2CNPh}] ( 2d) and [Pd(CH 3)(Cl){(bmim) 2CO}] ( 3c) have been determined and show a square planar geometry at palladium(II) with an appreciable diminished bite angle (85.6°) in 3c compared to 2d (88.5°). The molecular structure of 2d and 3c show both bisimidazole ligands coordinated via the ring nitrogen donors and inclination of the chelate ring bridge to the coordination plane (boat conformation). Low temperature NMR spectra indicate boat-to-boat inversion of the chelate ring in [Pd(CH 3)(CH 3CN){(mim) 2CO}] + ( 4b). Examples of the neutral and cationic complexes were tested in the Heck reaction and CO/ethylene copolimerisation respectively. The CO bridged bisimidazole complex ( 3b) exhibited high activity (TON of 100 000) in the Heck reaction whereas the closely related benzimidazole complex 3c was about half as active (TON of 53 000). Low activities were found for the cationic complex 4b in the CO/ethylene copolymerisation (TON 449).

4-[3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoic acid and heterocyclic-bridged analogues are novel retinoic acid receptor subtype and retinoid X receptor α agonists

Aromatic retinoids having a meta-substituted aromatic ring bridge, such as 4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoic acid and its 3,5-diaryl-substituted 4,5-dihydroisoxazole analogue, function as retinoid receptor panagonists by activating both retinoic acid and retinoid X receptors to induce gene transcription, and thereby provide novel scaffolds for retinoid drug development. Both classes of these ligand-inducible transcription factors are involved in mediating the inhibitory effects of retinoids on cancer cell growth.

Solid state and solution structure of the hetero-dimetallic complexes [Cp(CO)2Re{μ-C(OMe)(Ph)}Pt(COD)] and [Cp(CO)2Re{μ-CPh}Pt(COD)]+, containing bridging carbene and carbyne ligands

The reaction of the carbene complex [Cp(CO)2Re=C(OMe)(Ph)] with [Pt(COD)2] affords in high yield the novel complex [Cp(CO)2Re{μ-C(OMe)(Ph)}Pt(COD)] (2), containing a bridging carbene ligand. Reaction of 2 with (Me3O)BF4 results in removal of the carbene-bound methoxy group, with formation of the cation [Cp(CO)2Re{μ-CPh}Pt(COD)]+ (3), in which a bridging carbyne is present. Both the complexes contain only ligands coordinated through carbon atoms and represent the highest members, as far as the Pt:Re ratio is concerned, of the small family of phosphorous-free Pt–Re mixed metal complexes containing Pt-Re bonds. Their full 1H and 13C NMR characterization in solution and their single-crystal solid state diffractometric analysis are reported and discussed. The X-ray analysis evidenced the substantially symmetric nature of the carbene bridge in the dimetalla-cyclopropane ring of complex 2 [Re-Pt 2.7188(3), Re-(μ-C) 2.166(4) and Pt-(μ-C) 2.055(4) Å]. In complex 3 the bond length pattern within the three-membered ring is suggestive of a significant double-bond character for the Re-(μ-C) interaction [Re-Pt 2.707(1), Re-(μ-C) 1.904(9) and Pt-(μ-C) 1.981(8) Å]. Both complexes show a semi-bridging CO ligand, with Pt⋯C distances of 2.452(4) and 2.299(9) Å, in 2 and 3, respectively. The 13C NMR characterization showed that the Pt⋯CO interaction is also maintained in solution in both complexes. In cation 3 a libration of the ReCp(CO)2 fragment around the Pt-Re axis, fast down to 193 K, interchanges the two carbonyl locations observed in the solid state, as well as the environments of couples of COD carbon atoms, leading to an apparent Cs symmetry. The correlation between spectroscopic data and structural features (concerning bridging carbenes or carbynes and semi-bridging carbonyls) in the class of heterodimetallic M–Pt complexes is discussed.

One‐step synthesis of novel 2,4‐diaminopyrimidine antifolates from bridged alicyclic ketones and cyanoguanidine

AbstractA convenient one‐step reaction with cyanoguanidine was used to convert alicyclic ketones to previously undescribed 2,4‐diamino‐5,6,7,8‐tetrahydroquinazolines with a one‐, two‐, or three‐carbon bridge in the carbocyclic ring. Although the yields of the desired products were modest, the principal advantage of this one‐step process was that it provided easy access to a variety of novel bridged heterocyclic ring systems whose synthesis from sterically hindered ketones by other methods would have required multiple steps with an even lower overall yield. The products were tested as inhibitors of dihydrofolate reductases from Pneumocystis carinii, Toxoplasma gondii, and rat liver with a view to examining the effect of a space‐filling bridge on binding. The most potent and selective compound in the group was 4,6‐diamino‐3,5‐diazatricyclo[7.2.1.02,7]dodeca‐2,4,6‐triene (13), whose potency and selectivity approached those of trimethoprim, a drug commonly used to treat P. carinii and T. gondii infection. 3,5‐Diamino‐4,6‐diazatricyclo[6.2.1.02,7]‐undeca‐2,4,6‐triene (14), the analog of 13 with a one‐carbon rather than a two‐carbon bridge showed similar potency and selectivity against the T. gondii enzyme, but was a weak and nonselective inhibitor of P. carinii dihydrofolate reductase. The other compounds tested were likewise weak and nonselective.

Extension and revision of the von Baeyer system for naming polycyclic compounds (including bicyclic compounds)

Abstract These recommendations document the von Baeyer system for naming polycyclic ring systems described in Rules A-31, A-32 and B-14 of the Nomenclature of Organic Chemistry, Sections A, B, C, D, E, F and H, 1979 and R-2.4.2 of A Guide to IUPAC Nomenclature of Organic Compounds, 1993 and extend the system to cover more complex cases. It provides guidance on the naming of ring systems which previously the rules did not cover. The methods is to identify the main ring and main bridge which provide the basic bicyclic system and to number these atoms. Then all further bridges, whether or not they include additional atoms, are identified by indicating not only the number of atoms but also the two atoms to which the bridge is attached. The final name also indicated the number of rings and the total number of skeletal atoms in the ring systems. Heteroatoms, unsaturation and substituents are indicated in the usual way.

Sequence dependence of the reactivity of histidyl containing peptides with palladium(II) and platinum(II) complex ions. An NMR study

The reactions of the pentapeptide His-Pro-Gly-Ala-His with the complex salts [Pd(dien)(D2O)][NO3]2, [Pt(dien)(D2O)][NO3]2, [Pd(en)(D2O)2][NO3]2, cis-[Pt(NH3)2(D2O)2][NO3]2, K2PdCl4 and K2PtCl4 were studied in aqueous solutions, as a function of pD, by means of 1H, 13C and 195Pt NMR spectroscopies in one and two dimensions. In order better to understand the behavior of the ternary systems of the pentapeptide with the complex ion [Pd(dien)(D2O)][NO3]2 or [Pt(dien)(D2O)][NO3]2, the reactions of the tetrapeptide Pro-Gly-Ala-His with these complexes were also studied as a function of pD. The 1H and 13C NMR assignments were made by two dimensional homo- and hetero-nuclear experiments at various pD’s for both peptides. The complexes [Pd(dien)(D2O)][NO3]2 or [Pt(dien)(D2O)][NO3]2, react with Pro-Gly-Ala-His in acidic or alkaline media respectively to form mixtures of two isomers in which histidyl imidazole co-ordinates the metal through either N1 or N3. In neutral solution, the imidazole ring bridges two Pd(dien) moieties, bound to N1 and N3. In the presence of [Pd(dien)(D2O)][NO3]2 the histidyl-5 residue of the pentapeptide behaves in the same way as the one in the tetrapeptide, whereas the histidyl-1 residue reacts in acidic media through both imidazole N1 and N3 bridging two Pd(dien) moieties. The complex [Pd(en)(D2O)][NO3]2 or K2PdCl4 reacts with His-Pro-Gly-Ala-His in strongly acidic media (pD < 1.5) to form 1∶1 adducts with the histidyl-1 residue co-ordinated selectively to the metal ion forming NH2, N3 chelates. Similar products are formed by the reaction of the pentapeptide with cis-[Pt(NH3)2(D2O)2][NO3]2 or K2PtCl4 in slightly alkaline or acidic media respectively.

NMR conformational study of diamagnetic complexes of some triazatriacetate macrocycles

The conformational properties of the diamagnetic complexes formed by five triazatriacetic macrocyclic ligands with monovalent (alkaline) and divalent (alkaline-earth, Zn 2+ and Cd 2+) cations have been studied by proton nuclear magnetic resonance spectroscopy ( 1H NMR) in aqueous solution as a function of pH and temperature. These structurally related triazatriacetic ligands, 1,4,7-triazacyclononane- N,N′,N″-triacetic acid (NOTA), 1,4,7-triazacyclodecane- N,N′,N″-triacetic acid (DETA), 1,4,8-triazacycloundecane- N,N′,N″-triacetic acid (UNTA), 1,5,9-triazacyclododecane- N,N′,N″-triacetic acid (DOTRA), and 9,10-benzylidene-1,4,7-triazacyclotridecane- N,N′,N″-triacetic acid, (BUNTA) have triazamacrocyclic rings with different sizes and flexibilities, bearing three pendant acetate arms. In the case of the alkaline-earth, Zn 2+ and Cd 2+ cations, only one complex form (1:1) has been detected for all the ligands studied. In most cases the metal ion is coordinated to all the ligand ring nitrogens and to all or some of the carboxylate groups of the pendant arms, except when a poor fit of the cations into the macrocyclic hole occurs, such as for the Ba 2+ complexes of DETA, UNTA and DOTRA and the Ca 2+ and Sr 2+ complexes of BUNTA. The resonance patterns of the ring proton resonances, determined by the long lifetime of the metal-nitrogen bonds, indicate that the six-membered rings formed upon chelation are conformationally rigid and the five-membered rings are conformationally flexible. The multiplicity of the acetate proton resonances shows that the metal-oxygen bonds are long-lived or short lived depending whether the acetates are bound to nitrogens involved in two ring bridges of equal or unequal sizes.

Linked four-membered silicate rings: vibrational analysis of Gillespite

Raman spectra and lattice dynamics calculations are presented for the silicate mineral gillespite, BaFeSi4O10, which contains sheets of linked four-membered silicate rings. The results are analyzed in relation to earlier work done on the isolated four-membered ring silicate BaCuSi2O6 and to published claims that vibrational modes of four-membered rings are responsible for the sharp D 1“defect line” observed in the Raman spectra of SiO2 glass. The crystal structure of gillespite (space group P4/ncc or D ) consists of puckered Si4O12 rings, where each SiO4 tetrahedron is linked to two neighboring tetrahedra within a ring and to a third tetrahedron within a different ring. The rings are linked to each other in a staggered configuration to form sheets, which are also bonded together by Ba2+ and Fe2+. The calculation adjusts the bond bending and bond stretching force constants so that calculated fundamental mode frequencies best fit observed fundamental frequencies in the Raman spectra; eigenmodes associated with each calculated fundamental mode are then generated. Some eigenmodes calculated are unique to the gillespite structure, but many of the more localized four-membered ring modes are similar to those calculated for the four-membered rings in BaCuSi2O6 and for the three- and six-membered rings in the cyclosilicates studied earlier. The results for gillespite indicate that the Raman-active A 1g mode at 450 cm−1 is a four-membered ring bridging oxygen breathing mode that is mixed with other minor ring deformation displacements; because of this mixing, the calculated frequency of this mode is 45 to 61 cm−1 lower than that calculated for bridging oxygen binding breathing modes of puckered four-membered rings in BaCuSi2O6 and in simulated glass structures.

The Mass Spectrum of Cocaine

Abstract The current literature allows an analysis of the electron impact mass spectral fragmentations of cocaine (I). Using published high-resolution mass measurements as a reference, the mass spectra of several cocaine derivatives were examined—specifically those having individual functional group modifications at the nitrogen, alkyl ester group, aromatic ring and two-carbon bridge. Previously proposed major fragmentation pathways are supported by these data, and structures and mechanisms for lesser fragmentations are proposed. The relative intensities of the m/z 152 ions in the mass spectra of the cocaine diasteromers are rationalized based on these proposals.

Crystal Structure of Pig Pancreatic α‐amylase Isoenzyme II, in Complex with the Carbohydrate Inhibitor Acarbose

Two different crystal forms of pig pancreatic alpha-amylase isoenzyme II (PPAII), free and complexed to a carbohydrate inhibitor (acarbose), have been compared together and to previously reported structures of PPAI. A crystal form obtained at 4 degrees C, containing nearly 72% solvent, made it possible to obtain a new complex with acarbose, different from a previous one obtained at 20 degrees C [Qian, M., Buisson, G., Duée, E., Haser, H. & Payan, F. (1994) Biochemistry 33, 6284-6294]. In the present form, six contiguous subsites of the enzyme active site are occupied by the carbohydrate ligand; the structural data indicate that the binding site is capable of holding more than the five glucose units of the scheme proposed through kinetic studies. A monosaccharide ring bridging two protein molecules related by the crystal packing is located on the surface, at a distance of 2.0 nm from the reducing end of the inhibitor ligand; the symmetry-related glucose ring in the crystal lattice is found 1.5 nm away from the non-reducing end of the inhibitor ligand.

Sodium ion sensors based on dibenzo-16-crown-5 compounds with amide side arms

Abstract Lipophilic dibenzo-16-crown-5 compounds with amide-containing side arms attached to the central carbon atom of the three-carbon bridge in the polyether ring have been applied as neutral carriers for sodium ion-selective field-effect transistors (Na+-ISFET′s). ISFET′s based on these lariat ether amides exhibit excellent Na+/K+ selectivities (KNa′K Pot = 7 × 10−3) and Na+/H+ selectivities (KNa′H Pot = 3 × 10−3) with good selectivities for Na+ over other alkali metal cations and alkaline-earth metal cations. High sensor durability was obtained for these ISFET′s.

Pedestrian Ring Bridge

A key seaport for over 150 years, Bremerhaven, Germany provides an important gateway to Europe and overseas. Founded in 1827 with a current population of 130,000, Bremerhaven is rapidly developing from a commercial and industrial center to a cultural and recreational maritime center.

Pedestrian Ring Bridge

A key seaport for over 150 years, Bremerhaven, Germany provides an important gateway to Europe and overseas. Founded in 1827 with a current population of 130,000, Bremerhaven is rapidly developing from a commercial and industrial center to a cultural and recreational maritime center.

The Preparation of Salts of [Pd2(μ‐Se2N2)Cl6]2−, the First Adducts of Diselenium Dinitride

An Se2N2 ring bridges two PdCl3 units (structure shown on the right) in the title compounds, which are formed in the reaction of appropriate salts of [Pd2Cl6]2− with Se4N4. Unlike Se4N4, these Se2N2 adducts are not explosive.

Alkali Metal, Alkaline Earth Metal, and Ammonium Ion Selectivities of Dibenzo-16-Crown-5 Compounds with Functional Side Arms in Ion-Selective Electrodes

Potentiometric selectivities of 11 dibenzo-16-crown-5 compounds for alkali metal, alkaline earth metal, and ammonium ions have been determined in solvent polymeric membrane electrodes. The ionophores bear one or two pendent groups on the central carbon of the three-carbon bridge in the polyether ring. Side-arm variation includes OCH[sub 3], OCH[sub 2]CH[sub 2]OCH[sub 3], OCH[sub 2]CO[sub 2]C[sub 2]H[sub 5], OCH[sub 2]C(O)N(C[sub 2]H[sub 5])[sub 2], and OCH[sub 2]C(O)N(C[sub 5]H[sub 11])[sub 2] units. Attachment of a propyl group to the ring carbon that bears an extended, oxygen-containing side arm increases the selectivity for Na[sup +] relative to larger alkali metal and alkaline earth metal cations. For a given side arm, a linear relationship is obtained when the enhancement in Na[sup +] selectivity produced by attachment of a geminal propyl group is plotted against the diameter of the interference ion. Potentiometric responses of the dibenzo-16-crown-5 compounds are rationalized in terms of the crown ether ring size and the oxygen basicity, conformational positioning, and rigidity of the side arm. 22 refs., 3 figs., 2 tabs.

New phenylboronic esters derived from inositol [1

AbstractWe have prepared two new tetracyclic phenylboronic esters 4 and 5 derived from myo‐inositol and from 1,2‐O‐isopropylidene‐myo‐inositol, respectively. The structures of these compounds were established from NMR and IR spectra, elemental analyses, and an X‐ray diffraction study in the case of 4. Compound 4 is a tetracyclic derivative of the less stable conformer of inositol (five axial hydroxy groups and one equatorial) with two dioxaboroline rings at opposite faces of the six‐membered ring, one formed between the boron atom and the axial hydroxyl groups at C‐3 and C‐5 and the other between the boron atom and the hydroxyl groups at C‐4 and C‐6, and a dioxaborolidine ring bridging C‐1 and C‐2 at axial and equatorial positions. A similar structure was found for 5 with the difference that bridging C‐1 and C‐2 there is a dioxolane ring. The boron atoms are planar with their attached atoms, stabilized by retrocoordination between the boron and oxygen and carbon atoms, respectively. The two phenyl rings that are in the same face of the molecule are essentially parallel, with a dihedral angle between planes of 28.26 ± 0.79°.

Ring opening of strained-ring heterocycles containing nitrogen by an osmium cluster complex

The osmium cluster complex Os{sub 3}(CO){sub 10}({mu}-NCH{sub 2}CH{sub 2}CH{sub 2})({mu}-H) (1) was obtained in 34% yield from the reaction of Os{sub 3}(CO){sub 10}(NCMe){sub 2} with azetidine. Complex 1 was characterized crystallographically and shown to contain a four-membered NCH{sub 2}CH{sub 2}CH{sub 2} ring bridging two of the metal atoms via the nitrogen atom. When heated to 125{degrees}C, 1 was transformed to the new complex Os{sub 3}(CO){sub 10}[{mu}-N=C(H)Et]({mu}-H) (2; 27% yield) by an opening of the four-membered ring and a hydrogen shift. Crystal data: for 1, space group P2{sub 1}/c, a = 8.793 (2) A, b = 16.265 (2) A, c = 13.766 (4) A, {Beta} = 110.56 (1){degrees}, Z = 4, 1872 reflections, R = 0.039; for 2, space group P1, a = 92.73 (2){degrees}, {Beta} = 99.03 (2){degrees}, {gamma} = 81.52 (2){degrees}, Z = 6, 4862 reflections, R = 0.024. 16 refs. 2 figs.