Twist-boat Conformation Research Articles

Crystal structure of 2-[9-(2-hy-droxy-phen-yl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10-deca-hydro-acridin-10-yl]acetic acid.

The title compound, C21H21NO5, crystallizes with two mol­ecules in the asymmetric unit. In each mol­ecule, the central 1,4-di­hydro­pyridine ring adopts a shallow sofa conformations (with the C atom bearing the phenol ring as the flap), whereas the pendant cyclo­hexene rings both have twisted-boat conformations. Each mol­ecule features an intra­molecular O—H⋯O hydrogen bond, which closes an S(8) ring. In the crystal, the mol­ecules are linked by O—H⋯O, C—H⋯O and C—H⋯π inter­actions, forming a three-dimensional network.

Crystal structure of 2-amino-4-(4-chloro-phen-yl)-1-(4-methyl-phen-yl)-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carbo-nitrile.

In the title compound, C23H20ClN3O, each of the cyclo­hexene and 1,4-di­hydro­pyridine rings of the 1,4,5,6,7,8-hexa­hydro­quinoline ring system adopts a twisted-boat conformation. The dihedral angle between the two benzene rings is 11.52 (7)°. In the crystal, mol­ecules are linked through a pair of amino–nitrile N—H⋯N hydrogen bonds, forming inversion dimers. These assemble into a three-dimensional network via C—H⋯O and C—H⋯π inter­actions.

Crystal structure of methyl 4-(2-fluoro-phenyl)-6-methyl-2-sulfanylidene-1,2,3,4-tetra-hydro-pyrimidine-5-carb-oxy-late.

In the title compound, C13H13FN2O2S, the pyrimidine ring adopts a twist-boat conformation with the MeCN and methine-C atoms displaced by 0.0938 (6) and 0.2739 (3) Å, respectively, from the mean plane through the other four atoms of the ring. The 2-fluoro­benzene ring is positioned axially and forms a dihedral angle of 89.13 (4)° with the mean plane through the pyrimidine ring. The crystal structure features N—H⋯O, N—H⋯S and C—H⋯O hydrogen bonds that link mol­ecules into supra­molecular chains along the b axis. These chains are linked into a layer parallel to (10-1) by C—H⋯π inter­actions; layers stack with no specific inter­actions between them.

Crystal structure of (1S,3R,8R,9R,10S)-2,4,6-tris-(2,2-di-chloro-3,7,7,10-tetra-methyl-tri-cyclo-[6.4.0.0(1,3)]dodec-9-yl)cyclo-triboroxane.

The title compound, C48H75B3Cl6O3, was synthesized in two steps from β-himachalene (3,5,5,9-tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo-hept-ene), which was isolated from the essential oil of the Atlas cedar (Cedrus Atlantica). The mol-ecule consists of an almost planar cyclo-triboroxane ring [maximum deviation = 0.036 (2) Å] linked to three identical fused ring systems with different conformations. Each of the three attached ring systems is built up from a seven-membered ring to which a six- and a three-membered ring are fused. The three six-membered rings have a twist-boat conformation, whereas the seven-membered rings display boat, chair and twist-boat conformations. The dihedral angles between the central boroxane ring and the mean planes of the attached six-membered rings are 63.67 (18), 54.89 (2) and 56.57 (19)°. The crystal packing is governed only by van der Waals inter-actions.

Crystal structure of (E)-4-(acetoxyimino)-N-allyl-3-isopropyl-2,6-diphenylpiperidine-1-carbothioamide

The title compound, C26H31N3O2S, crystallizes with two mol­ecules (A and B) in the asymmetric unit. In each case, the piperidine ring exists in a twist-boat conformation. The dihedral angle between the phenyl rings is 46.16 (12)° in mol­ecule A and 44.95 (12)° in mol­ecule B. In both mol­ecules, the allyl side chain is disordered over two orientations in a 0.649 (9):0.351 (9) ratio for mol­ecule A and 0.826 (10):0.174 (10) ratio for mol­ecule B. In the crystal, neither mol­ecule forms a hydrogen bond from its N—H group, presumably due to steric hindrance. A+A and B+B inversion dimers are formed, linked by pairs of weak C—H⋯O hydrogen bonds enclosing R 2 2(22) ring motifs.

Crystal structure of 16-hy-droxy-4,4,10,13,14-penta-methyl-17-(6-methyl-hept-5-en-2-yl)-4,5,6,9,10,11,12,13,14,15,16,17-dodeca-hydro-1H-cyclo-penta-[a]phenanthren-3(2H)-one.

The title compound, C30H48O2, contains a fused four-ring triterpenoid system. In the mol­ecule, the two cyclo­hexane rings adopt a chair conformation and a twist boat conformation, respectively, the central cyclo­hexene ring adopts a half-chair conformation whereas the five membered ring adopts an envelope conformation. In the crystal, O—H⋯O hydrogen bonds between the hy­droxy and carbonyl groups of adjacent mol­ecules link the mol­ecules into supra­molecular chains propagating along the b-axis direction.

Crystal structure of (1S,3R,8R,9S,10R)-10-bromo-methyl-2,2-di-chloro-9,10-ep-oxy-3,7,7-tri-methyl-tri-cyclo-[6.4.0.0(1,3)]dodeca-ne.

The title compound, C16H23BrCl2O, was synthesized in three steps from β-himachalene (3,5,5,9-tetra­methyl-2,4a,5,6,7,8-hexa­hydro-1H-benzo­cyclo­heptene), which was isolated from the essential oil of the Atlas cedar (cedrus atlantica). The mol­ecule is built up from two fused six- and seven-membered rings, each linked to a three-membered ring. The six-membered ring has a screw-boat conformation, whereas the seven-membered ring displays a twist-boat conformation. The absolute structure was established unambiguously from anomalous dispersion effects.

Synthesis, characterisation, stereochemistry and dynamic NMR studies of N-nitroso and N-formyl-t-3-isopropyl-r-2,c-6-bis(4-methoxyphenyl)piperidin-4-ones

The synthesis, characterisation and stereochemical investigations were made for N-nitroso (2) and N-formyl (3) derivatives of t-3-isopropyl-r-2,c-6-bis(4-methoxyphenyl)piperidin-4-one (1) using IR, mass, 1D and 2D NMR spectral studies. The compound 1 prefers to adopt a chair conformation with equatorial orientations of all substituents. The compounds 2 and 3 showed doubling of all the NMR spectral signals corresponding to syn and anti rotamers at RT and 223K, respectively. The syn and anti rotamers of 2 exist in an equilibrium between alternate chair (CA) and twist boat (TB1) conformations, respectively. The syn and anti rotamers of 3 exist in TB1 conformation. The stereodynamics of compounds 2 and 3 have been investigated using dynamic 1H NMR spectra and the calculated average energy barriers for N-NO and N-CHO rotations are found to be 77.76kJmol−1 and 68.18kJmol−1, respectively.

Crystal structure of pseudoguainolide.

The lactone ring in the title mol­ecule, C15H22O3 (systematic name: 3,4a,8-tri­methyl­dodeca­hydro­azuleno[6,5-b]furan-2,5-dione), assumes an envelope conformation with the methine C atom adjacent to the the methine C atom carrying the methyl substituent being the flap atom. The other five-membered ring adopts a twisted conformation with the twist being about the methine–methyl­ene C—C bond. The seven-membered ring is based on a twisted boat conformation. No specific inter­actions are noted in the the crystal packing.

Crystal structure of 2-chloro-1-(3-methyl-2,6-di-phenyl-piperidin-1-yl)ethanone.

In the title compound, C20H22ClNO, the piperidine ring has a twist-boat conformation. There is an intra­molecular C—H⋯π inter­action involving the two phenyl rings which are inclined to one another by 84.91 (7)°. In the crystal, mol­ecules are linked via C—H⋯O hydrogen bonds, forming helical chains along [010]. The chains are linked by C—H⋯π inter­actions, forming sheets parallel to (100).

Crystal structure of 2-chloro-1-(3-ethyl-2,6-di-phenyl-piperidin-1-yl)ethanone.

In the racemic title compound, C21H24ClNO, the dihedral angle between the planes of the benzene rings is 86.52 (14)° and those between the benzene rings and the piperidine ring are 61.66 (14) and 86.39 (14)°. The piperidine ring adopts a twisted boat conformation. No directional inter­actions could be detected in the crystal.

TOAC Spin Label Conformation Resolved by MD Simulation of Membrane-Bound Phospholamban

We have used all-atom molecular dynamics (MD) simulation to determine the conformational occupancy of the nitroxide spin label TOAC attached to membrane-bound phospholamban (PLB), as needed for interpretation of EPR spectra. EPR spectroscopy is sensitive primarily to the dynamic angular distribution of the probe principal axis relative to the magnetic field, θHP. MD simulations determine directly the orientation of the probe principal axis relative to the α-helix axis, θMP. Previously, θMP has been determined from X-ray crystallography of TOAC on α-helical peptides, which have indicated sole occupancy of a twistboat conformation, with θMP = 13.3° (Marsh 2006 JMagRes). We have employed all-atom MD simulations to determine the distribution of θMP values for TOAC bound to PLB. The PLB structure (PDB ID: 2KB7) was mutated with TOAC at residues 11, 24, 36, or 46, and placed in Monte-Carlo-generated lipid bilayers composed of either DOPC or DMPC:POPC. MD simulations were performed using NAMD with the CHARMM36 force field. Trajectories were computed to 100ns for chair, boat, and twistboat starting conformations of TOAC. Time-averaged geometry of PLB α-helices in the lipid bilayer membrane were calculated, and results agreed with published NMR data, validating the MD results. Furthermore, angle distributions in the probe frame - (θHP, ϕHP) and (θMP, ϕMP) - were calculated, indicating a bimodal TOAC occupancy model with sensitivity to label location. Coupling MD-derived conformational models with EPR data fitting has improved determination of the conformational distribution of PLB in a lipid bilayer and will allow us to determine PLB orientations in other conditions such as when bound to SERCA.

Crystal structure of (Z)-3-(4-meth-oxy-benzyl-idene)-2,3-di-hydro-benzo[b][1,4]thia-zepin-4(5H)-one.

In the title compound, C17H15NO2S, the two C atoms linking the S and carbonyl C atoms of the seven-membered thia­zepine ring are disordered over two sites, with occupancies of 0.511 (4) and 0.489 (4); both disorder components adopt distorted twist-boat conformations. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds link inverted-related mol­ecules into dimers, incorporating R 1 2(6) and R 2 2(8) ring motifs; the acceptor carbonyl O atom is bifurcated. These dimers are further linked by C—H⋯O hydrogen bonds, forming supra­molecular tapes running along the a axis.

A twist on facial selectivity of hydride reductions of cyclic ketones: twist-boat conformers in cyclohexanone, piperidone, and tropinone reactions.

The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin–Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH4) but not with a bulky hydride (lithium triisopropylborohydride).

Crystal structure of bis-[(5-amino-1H-1,2,4-triazol-3-yl-κN (4))acetato-κO]di-aqua-nickel(II) dihydrate.

The title compound, [Ni(C4H5N4O2)2(H2O)2]·2H2O, represents the first transition metal complex of the novel chelating triazole ligand, 2-(5-amino-1H-1,2,4-triazol-3-yl)acetic acid (ATAA), to be structurally characterized. In the mol-ecule of the title complex, the nickel(II) cation is located on an inversion centre and is coordinated by two water mol-ecules in axial positions and two O and two N atoms from two trans-oriented chelating anions of the deprotonated ATAA ligand, forming a slightly distorted octa-hedron. The trans angles of the octa-hedron are all 180° due to the inversion symmetry of the mol-ecule. The cis-angles are in the range 87.25 (8)-92.75 (8)°. The six-membered chelate ring adopts a slightly twisted boat conformation with puckering parameters Q = 0.542 (2) Å, Θ = 88.5 (2) and ϕ = 15.4 (3)°. The mol-ecular conformation is stabilized by intra-molecular N-H⋯O hydrogen bonds between the amino group and the chelating carboxyl-ate O atom of two trans-oriented ligands. In the crystal, the complex mol-ecules and lattice water mol-ecules are linked into a three-dimensional framework by an extensive network of N-H⋯O, O-H⋯O and O-H⋯N hydrogen bonds.

Simulation of force spectroscopy experiments on galacturonic acid oligomers.

Pectins, forming a matrix for cellulose and hemicellulose, determine the mechanics of plant cell walls. They undergo salient structural changes during their development. In the presence of divalent cations, usually calcium, pectins can form gel-like structures. Because of their importance they have been the subject of many force spectroscopy experiments, which have examined the conformational changes and molecular tensions due to external forces. The most abundant unit present in the pectin backbone is polygalacturonic acid. Unfortunately, experimental force spectroscopy on polygalacturonic acid molecules is still not a trivial task. The mechanism of the single-molecule response to external forces can be inferred by theoretical methods. Therefore, in this work we simulated such force spectroscopy experiments using the Enforced Geometry Optimization (EGO) method. We examined the oligomeric (up to hexamer) structures of α-D-galacturonic acid exposed to external stretching forces. The EGO simulation of the force spectroscopy appropriately reproduced the experimental course of the enforced conformational transition: chair →inverted chair via the twisted boat conformation(s) in the pyranose ring of α-D-galacturonic acid. Additionally, our theoretical approach also allowed to determine the minimum oligomer size adequate for the description of nano-mechanical properties of (poly)-α-D-galacturonic acid.

Pseudorotational landscape of seven-membered rings: the most stable chair and twist-boat conformers of ε-caprolactone.

The conformational landscape and ring-puckering properties of ε-caprolactone have been analyzed by using microwave spectroscopy and quantum chemical calculations. Two conformers were detected in a supersonic jet expansion, the most stable form being a chair containing the ester group in its rectangular flap. This conformation benefits from reduced CH2 bond eclipsing and angle strain, while π-electron delocalization in the ester group is increased. The derived effective structure of the chair form satisfactorily agrees with the calculated near-equilibrium structure. A twist-boat conformer was also identified (9.4 kJ mol(-1) higher in energy at CCSD(T)/aug-cc-pVTZ level), and was located in the boat-twist-boat pseudorotation cycle of the seven-membered ring. Three other low-energy conformers were investigated and characterized in terms of the four puckering coordinates of the seven-membered ring. Potential interconversions in the four-dimensional conformation space are also discussed.

Synthesis, spectral and single crystal X-ray diffraction studies of novel O-(Carboalkoxy)methyl oxime ethers of 3-alkyl and 3,5-dialkyl-1-methyl-2,6-diphenylpiperidin-4-ones

A series of novel O-(Carboalkoxy)methyl oxime ether derivatives of 3-alkyl and 3,5-dialkyl-1-methyl-2,6-diphenylpiperidin-4-ones were synthesized and characterized through FT-IR, Mass, 1H NMR, 13C NMR, 1H1H COSY, 1H13C COSY and NOESY spectral techniques. The stereocontrolled formation of E-isomer exclusively in all the cases was confirmed by NMR spectral analysis. A1,3 strain induced epimerization of C5 carbon in the case of compounds 18 and 23 was also observed. The preferred conformation of compounds 16, 17, 20, 21, 22 and 25 was found to be chair and for compounds 19 &24 it was boat while compounds 18 and 23 adopt a twist boat conformation as observed by 1H NMR and NOESY spectra. The solid state geometry of compound 16 was established by single crystal X-ray diffraction analysis.

Ethyl 2,6-bis-(4-bromo-phen-yl)-1-iso-cyano-4-oxo-cyclo-hexa-necarboxyl-ate.

In the title compound, C22H19Br2NO3, the central oxo­cyclo­hexane ring is in a twist-boat conformation; all the substituents (one eth­oxy­carbonyl and two aryl groups) are located in equatorial orientations. One of the –CH2– groups and the opposite –CH– group bearing a bromo­benzene substituent form the flagpoles of the twist-boat. The dihedral angle between the aromatic rings is 76.4 (4)°. In the crystal, weak C—H⋯O inter­actions link the mol­ecules into C(5) chains propagating in the [010] direction. A short Br⋯O contact of 3.254 (4) Å is observed.

Ethyl 2,6-bis-(4-chloro-phen-yl)-1-iso-cyano-4-oxo-cyclo-hexa-necarboxyl-ate.

In the title compound, C22H19Cl2NO3, the central six-membered ring is in a twist-boat conformation. The two aryl groups are in equatorial positions, trans to each other and with a dihedral angle of 77.50 (2)° between them. One of the least hindered –CH2– groups and one of the aryl-substituted C atoms, with its axial H atom, are in the flagpole positions. The eth­oxy­carbonyl group is in an equatorial position and is cis to the second aryl group. In the crystal, molecules are linked via weak C—H⋯O hydrogen bonds, forming chains along [010].