Cyclohexane Core Research Articles

Theoretical Investigation of Macrodipoles in Supramolecular Columnar Stackings

Supramolecular columnar assemblies are known to form intrinsic macrodipoles, which play an important role in intercolumnar interactions and govern the self-assembly on the mesoscale. A prominent class that provides this feature are trisamide derivatives, namely, 1,3,5-benzenetrisamides and 1,3,5-cyclohexanetrisamides. The understanding of how subtle changes in the chemical structure influence the columnar order and consequently the macrodipole formation is of fundamental interest. Here we report on the theoretical investigation of trisamide derivatives and how the formed macrodipole is related to the properties of the columnar aggregates. Calculations were carried out on a semiempirical level using the PM6 approximation, which is able to treat weak interactions like hydrogen bonding and dispersion forces with a sufficient accuracy. We have compared the influence of a benzene core with a cyclohexane core on the macrodipole formation. It was revealed that columnar aggregates based on 1,3,5-cyclohexanetrisamides have much higher dipole moments than those formed with aromatic cores. A cooperative effect was found during aggregation, as longer aggregates show stronger hydrogen bonding, thereby facilitating the addition of the next molecule. We have also investigated the influence of the amide connection on the strength of the formed macrodipole. The trends observed for the macrodipole strength correlate with the calculated heat of formation. If the amide groups are inverted, the strength of the macrodipole is reduced and the negative heat of formation is increased. HOMO-LUMO gaps were correlated with the inverse of the dipole moment per monomer unit, thus indicating that the macrodipole might act as a perturbation to the supramolecular assemblies.

A Highly Efficient Self‐Assembly of Responsive C2‐Cyclohexane‐Derived Gelators

The rational design and synthesis of a family of effective low-molecular-weight gelators (LMWGs) with a modular architecture based on a C(2) -1,4-diamide cyclohexane core are reported. Due to the high symmetry, the gelators are initially well distributed in solution and no trapped aggregates are formed before the assembly is triggered. The subsequent self-assembly process, which results in the formation of versatile gels, is highly efficient and can be triggered and tuned due to its remarkable dependence on the pH of solution. The assembly of different gelators is found to be closely related to the pK(a) of the corresponding functional substituents on the LMWGs. Primary cell culture experiments reveal that the hydrogels made under physiological conditions are promising as potential tailor-made microenvironments.

Total Synthesis of (−)‐atrop‐Abyssomicin C

Rolling in the deep: An enantioselective synthesis of a marine antibiotic (−)-atrop-abyssomicin C (see scheme) is described. The key steps of the synthetic sequence are the application of dual catalysis in the formation of the cyclohexane core, the gold-catalyzed formation of a tricyclic spirotetronate unit, and a highly efficient eleven-membered ring closure by a Nozaki–Hiyama–Kishi reaction.

Synthesis of the Cyclohexane Core of Phomactins and a New Route to the Bicyclo[9.3.1]pentadecane Diterpenoid Skeleton

Conjugate reduction of an enone accompanied by in situ intramolecular aldol condensation was used to construct the tetrasubstituted cyclohexane nucleus of phomactins. Subsequent relay ring-closing metathesis completed the nine-membered ansa bridge of the diterpenoid framework.

Total Synthesis of (+)‐Clavolonine, (−)‐Deacetylfawcettiine, and (+)‐Acetylfawcettiine

Three lycopodium alkaloids have been prepared by using a new strategy for constructing the central cyclohexane core (see scheme; o-DPPB=ortho-diphenylphosphanyl benzoyl). Thus stereoselective synthesis relying on substrate control was implemented; the key step involved a sequence of a (o-DPPB)-directed hydroformylation/carbonylene reaction and (o-DPPB)-directed hydroformylation.

Selective Recognition of Alkyl Pyranosides in Protic and Aprotic Solvents

The design and synthesis of receptors capable of selective, noncovalent recognition of carbohydrates continues to be a signature challenge in bioorganic chemistry. We report a new generation of tripodal receptors incorporating three pyridine (compound 2) or quinoline (compound 3) rings around a central cyclohexane core for use in molecular recognition of monosaccharides in apolar and polar protic solvents. These tripodal receptors were investigated using (1)H NMR, UV, and fluorescence titrations in order to determine their binding abilities toward a set of octyl glycosides. Receptor 2 displayed the highest binding affinity reported to date for noncovalent 1:1 binding of an alpha-glucopyranoside in chloroform (Ka = 212,000 +/- 27,000 M(-1)) and an approximately 8-fold selectivity for the alpha anomer over the beta anomer of the glucopyranoside. Most importantly, 2 retained its micromolar range of affinities toward monosaccharides in a polar and highly competitive solvent (methanol). The quinoline variant 3 also displayed micromolar binding affinities for selected monosaccharides in methanol (as measured by fluorescence) that were generally smaller than those of 2. Compound 3 was found to follow a selectivity pattern similar to that of 2, displaying higher affinities for glucopyranosides than for other monosaccharides. The binding stoichiometry was estimated to be 1:1 for the complexes formed by both 2 and 3 with glucopyranosides, as determined by Job plots. Nuclear Overhauser effect spectroscopy allowed for the derivation of a binding model consistent with the observed selectivities.

A Practical Synthesis of a γ-Secretase Inhibitor

A practical and scaleable synthesis of the gamma-secretase inhibitor 1 is reported. The inhibitor consists of a central trisubstituted cyclohexane core with appended propionic acid, 2,5-difluorophenyl, and 4-chlorophenylsulfonyl moieties. Two alternative synthetic strategies, proceeding by way of a common disubstituted cyclohexanone derivative 5, were studied. In the preferred route, conjugate reduction of acrylonitrile derivative 4 with L-Selectride configures the desired relative stereochemistry of the cyclohexane core with >99.9:0.1 dr. A second strategy, based on catalyst-controlled hydrogenation of racemic cyclohexene derivative 2, is more convergent but less diastereoselective (up to 75:25 dr). The common cyclohexanone intermediate 5 was constructed by a regioselective Diels-Alder condensation of a 1,1-disubstituted vinyl sulfone 6 with 2-trimethylsiloxybutadiene.

Expeditious synthesis of novel NK 1 antagonists based on a 1,2,4-trisubstituted cyclohexane

A stereoselective asymmetric route to novel potent NK 1 antagonists based on a 1,2,4-trisubstituted cyclohexane core is discussed.

A Stereoselective Synthesis of (‐)‐Tetrodotoxin.

An asymmetric synthesis of the fugu fish poison, (−)-tetrodotoxin, is described. The route to this extraordinary target employs a number of unique transformations, foremost of which are two stereospecific C−H bond functionalization reactions. Accordingly, Rh-catalyzed carbene and nitrene C−H insertions facilitate rapid entry to the cyclohexane core of the natural product and make possible the late-stage installation of the tetrasubstituted carbinolamine center.

The polyhomologation of 1-boraadamantane: mapping the migration pathways of a propagating macrotricyclic trialkylborane.

Trialkyl and triaryl organoboranes undergo multiple, repetitive homologations upon reaction with dimethylsulfoxonium methylide (1). This multiple homologation reaction, or polyhomologation, produces polymethylene in a living reaction. Applying the polyhomologation reaction to cyclic and polycyclic organoboranes permits the construction of unique oligomeric and polymeric architectures that are not readily accessible by standard olefin polymerization. The polyhomologation of 1-boraadamantane.THF (2) by ylide 1 generates novel macrotricyclic trialkylboranes (3). The oxidation of these macrocyclic organoboranes generates a three-armed star polymethylene polymer (4) incorporating a cis,cis-1,3,5-trisubstituted cyclohexane core. Interestingly, only one-third of the initiators lead to product formation, resulting in an observed degree of polymerization 3 times higher than expected. Close examination of the initial stages of polymerization show that 1-boraadamantane.THF reacts with 1 equiv of 1 to afford a monohomologated product. Subsequent homologations were found to contain branch points leading to isomeric tricyclic products after the third, fourth, and fifth methylene insertions. At these stages of homologation, all of the propagating species result in tricyclic trialkylborane cages with collapsed, inverted pyramidal boron centers that are substantially less reactive toward ylide. Approximately two-thirds of the species discontinue polymerization at these stages. However, one-third of these species continue to propagate and eventually result in the formation of giant macrotricyclic polymers of narrow polydispersity. Molecular modeling and kinetic simulation have aided in the analysis of the probable pathways through which the reaction proceeds.

A Stereoselective Synthesis of (−)-Tetrodotoxin

An asymmetric synthesis of the fugu fish poison, (-)-tetrodotoxin, is described. The route to this extraordinary target employs a number of unique transformations, foremost of which are two stereospecific C-H bond functionalization reactions. Accordingly, Rh-catalyzed carbene and nitrene C-H insertions facilitate rapid entry to the cyclohexane core of the natural product and make possible the late-stage installation of the tetrasubstituted carbinolamine center.

1-Boraadamantane blows its top, sometimes. The mono- and polyhomologation of 1-boraadamantane.

[reaction: see text] 1-Boraadamantane.THF (3) reacts with 1 equiv of dimethylsulfoxonium methylide (4) to afford a monohomologated product. The polyhomologation of 1-boraadamantane.THF by ylide 4 followed by oxidative cleavage generates star polymethylene polymers incorporating a cyclohexane core. However, only one-third of the initiators lead to product formation, resulting in an observed degree of polymerization three times higher than expected. The polyhomologation of 3 was found to contain branch points after the fourth and fifth methylene insertions. At the branch points, the propagating species either terminate in tricyclic trialkylborane cages with collapsed, pyramidal inverted boron centers that are unreactive toward ylide or they continue in uninterrupted polymerization and eventually result in the formation of giant "tube-like" structures such as 5.

Vitrified Chiral−Nematic Liquid Crystalline Films for Selective Reflection and Circular Polarization

Nematic and left-handed chiral−nematic liquid crystals comprising methoxybiphenylbenzoate and (S)−(−)-1-phenylethylamine pendants to a cyclohexane core were synthesized and characterized. Although pristine samples were found to be polycrystalline, thermal quenching following heating to and annealing at elevated temperatures permitted the molecular orders characteristic of liquid crystalline mesomorphism to be frozen in the glassy state. Left at room temperature for 6 months, the vitrified liquid crystalline films showed no evidence of recrystallization. An orientational order parameter of 0.65 was determined with linear dichroism of a vitrified nematic film doped with Exalite 428 at a mole fraction of 0.0025. Birefringence dispersion of a blank vitrified nematic film was determined using a phase-difference method complemented by Abbe refractometry. A series of vitrified chiral−nematic films were prepared to demonstrate selective reflection and circular polarization with a spectral region tunable from blue...

Definition of Several Control Elements Relevant to the Stereodefined Serial Elaboration of Belted Poly(spirotetrahydrofurans) Fitted with a Cyclohexane Core.

The stereochemistry of the condensations of 2-cyclohexenones, alpha-arylidenecyclohexanones, and alpha-(tert-butyldimethylsiloxy)cyclohexanones carrying one or two (both syn and anti) spirotetrahydrofuran units adjacent to the carbonyl with allyl organometallics (especially indium) and with the Normant reagent (ClMgO(CH(2))(3)MgCl) is described. Good levels of anti stereoselection are observed in the alpha-arylidene series. Subsequent cyclization generates a second (or third) tetrahydrofuran ring possessing trans vicinal oxygens. Useful levels of matched and mismatched diastereoselection are also attainable by prior alpha-oxygenation. The intrinsic differences in diastereomer production between indium and magnesium organometallics are highlighted. A clear distinction regarding the anticipated direction of stereoselectivity is made on the grounds of chelation capabilities and the intra- or intermolecularity of carbon-carbon bond formation. Finally, the two protocols that are described in detail are shown to be iterative, a feature that augurs well for ultimately accessing the eight possible hexaspirocyclohexanes in an efficient and stereocontrolled manner.

Stereoselective synthesis of the tetrasubstituted cyclohexane core of a monocyclic mevinic acid analogue

Stereoselective synthesis of a 1,2,3,4-tetrasubstituted cyclohexane 23, intermediate towards Karanewsky's monocyclic Compactin analogue 3, has been performed starting from levoglucosan 4.

Synergisms, structure-material relations and display performance of novel fluorinated alkenyl liquid crystals

Abstract Several new classes of low polarity, low viscosity and optically weakly anisotropic two and three ring fluorinated liquid crystals with alkenyl side chains are presented. Synergisms which lead to a number of favourable material properties are shown to result from systematic changes of (a) para and lateral fluorination of the benzene ring in the rigid cores, (b) variations of double bond positions in the alkenyl side chains and (c) from replacing cyclohexane core rings by dioxane rings. A broad range of dielectric anisotropies −0.3 < Δ∊ < 13, broad nematic meso-phases, low rotational, λ and bulk viscosities, n, (22°C) < 10cP as well as visco elastic ratios as low as λ/k (22°C) = 3.8 × 10–12m-12s-1 follow; were K = K11 + (K33 - 2K22)/4. As a consequence a wide range of optical threshold voltages V10 and short response times result in field-effect liquid crystal displays. The low ratios κ/Δ∊ of the heterocyclic representatives among the new compounds lead in twisted nematic displays to threshold vol...