Achiral Derivatives Research Articles

Structurally diverse isobutylamides from Zanthoxylum nitidum

Five pairs of new racemic alkamides (1a/1b and 4a/4b-7a/7b) and two new achiral derivatives (2–3), as well as five known ones (8–12), were purified from the 95% EtOH extract of Zanthoxylum nitidum. Their structures were elucidated based on spectroscopic analyses (NMR and HR-ESI-MS), electronic circular dichroism (ECD) and NMR calculations. The enantiomeric separation was successfully achieved by chiral-phase HPLC-ECD measurements. Among all the isolates, compounds 2, 3, and 10 showed inhibitory effects against five human cancer cell lines, with IC50 values in range of 18.51–48.03 μM.

Flavin mimetics: Synthesis and photophysical properties

We report the synthesis of new isoalloxazines using a microwave-assisted approach to make N -substituted-2-nitroanilines followed by one-pot reduction and condensation via Hemmerich’s method. The influence of substituents on positions 7, 8, and 10 of flavin core on the optical properties is investigated. The aliphatic functionalities on N10 give rise to quantum yields of 0.7, while aromatic side-chains quench fluorescence. Relaxed geometries (DFT) of chiral and achiral derivatives have been used for TD-DFT calculations, which yielded good agreement with the experimental UV and CD data.

Circularly Polarized Luminescence from Chiral Supramolecular Polymer and Seeding Effect.

H-bonding driven J-type aggregation and cooperative supramolecular polymerization of a sulfur-substituted chiral naphthalene-diimide (NDI)-derivative (S,S)-NDI-2 in decane leads to remarkable enhancement of fluorescence quantum yield (43.3 % from 0.5 % in the monomeric state) and intense CPL signal in the aggregated state with a high luminescence dissymmetry factor (glum ) of 4.6×10-2 . A mixture of NDI-2 with a structurally similar NDI-derivative NDI-1 (mixture of racemic (S,S)- and (R,R)- isomers and the achiral derivative) in 1:9 (NDI-2/NDI-1) ratio, when heated and slowly cooled to room temperature, showed no enhanced CD band, indicating lack of any preferential helicity. However, when a monomeric solution of the NDI-1 in tetrahydrofuran (THF) was injected to preformed seed of NDI-2 in decane, a prominent CD signal appeared, indicating chiral amplification resulting in induced CPL with high glum value of 2.0×10-2 from mostly (>98.5 %) diastereomeric mixture.

Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class I HDAC Enzymes and Cancer Cell Proliferation.

AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.

Anti-cancer activity of m-carborane-containing trimethoxyphenyl derivatives through tubulin polymerization inhibition.

m-Carborane-containing compound 1a was identified as a cell growth inhibitor from a random screening of a boron compound library. As 1a is a mixture of diastereomers due to the presence of two chiral carbons, we designed achiral derivatives 2-4 and studied the structure-activity relationships of the methoxy groups on the benzene ring. 3,4,5-Trimethoxybenzyl derivative 2a and 3,4,5-trimethoxybenzoyl derivative 3a showed more potent anti-cancer activity against the human breast cancer cell line MDA-MB-453 than lead compound 1a. Compound 3a inhibited tubulin polymerization in a dose-dependent manner.

Enumeration of Stereoisomers of Chiral and Achiral Derivatives of Monocyclic Cycloalkanes Having Heteromorphous Alkyl Substituents with Distinct Length <i>k</i>

A combinatorial method based on the determination of the averaged weight of permutations controlling the chirality/achirality fittingness of 2n substitution sites of the monocyclic cycloalkane allows to obtain generalized functional equations for direct enumeration of enantiomers pairs and achiral skeletons of any derivatives of monocyclic cycloalkanes having heteromorphic alkyl substituents with the distinct length k with the empirical formula , wherein at least two alkyl groups of the distinct size each. is the number of alkyl radicals of the system verifying the relation . The integer sequences of enantiomer pairs and achiral skeletons are given for substituted derivatives of monocyclic cycloalkane for n = 3, 4 and k = 3, 4, 5. The composite stereoisomerism of this particular compound is also highlighted.

Activation and recyclization of a benzocyclobutenone derivative catalyzed by a chiral Rh(I) complex based on DFT investigations

The R- and S-activation and cyclization channels of an achiral benzocyclobutenone derivative to a pair of enantiomers with poly-fused rings were investigated systematically based on full optimization with the BP86 functional in gas phase and the M06 functional in tetrahydrofuran (THF). Both the BP86 and M06 methods show that the R-channel is energetically more favorable than the S-channel in gas phase and in THF. The rate-determining step for the R-channel is the C–C activation with a barrier of 17.2 kcal/mol in THF and 11.8 kcal/mol in gas phase, but for the S-channel, the rate-determining step is the pentatomic ring formation process with a barrier of 25.6 kcal/mol in THF and 22.3 kcal/mol in gas phase.

Preparation of Chiral Polydiacetylene Films by Using Three-Photon Polymerization.

Asymmetric polymerization of polydiacetylene (PDA) from commercially available achiral derivative of diacetylene monomer using circularly polarized pulse laser is demonstrated. Chiral source was only circularly polarized laser, and irradiation of left- and right-circularly polarized light effectively promoted the polymerization of chiral PDAs with opposite handedness. Difference between the laser wavelength and the absorption peak of monomer suggested the contribution of the multiphoton excitation to the photo-polymerization. Laser power dependence of the polymerization rate indicated the possibility of three-photon polymerization.

Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes

Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 μM for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.

Octasubstituted dibenzochrysenes: discotic liquid crystals with a twisted core

Octafunctionalised dibenzochrysenes are prepared in order to study the liquid crystalline properties that have chiral and achiral peripheral aliphatic chains. The syntheses of dibenzochrysene derivatives are achieved by a conventional method that has been developed recently. The achiral derivatives that have long peripheral aliphatic chains exhibit hexagonal and rectangular columnar mesophases over a wide thermal range, whereas those with short chains exhibit only hexagonal or more ordered (not identified) columnar phases, such as the columnar plastic. The chiral derivates exhibit only the hexagonal columnar mesophase. The nature of these mesophases is investigated by polarising optical microscopy and X-ray diffraction studies.

Enhancement of the Antimalarial Activity of Ciprofloxacin Using a Double Prodrug/Bioorganometallic Approach

The derivatization of the fluoroquinolone ciprofloxacin greatly increases its antimalarial activity by combining bioorganometallic chemistry and the prodrug approach. Two new achiral compounds 2 and 4 were found to be 10- to 100-fold more active than ciprofloxacin against Plasmodium falciparum chloroquine-susceptible and chloroquine-resistant strains. These achiral derivatives killed parasites more rapidly than did ciprofloxacin. Compounds 2 and 4 were revealed to be promising leads, creating a new family of antimalarial agents.

Helicity control in chiral gelation of achiral coumarin derivatives

Achiral coumarin derivatives spontaneously undergo chiral gelation to give twisted ribbon-like gels in cyclohexane. This kind of chiral gelation of achiral molecules necessarily forms right- and left-handed helical gels. We successfully controlled the helicity in the presence of small amounts of enantiomerically pure coumarins in the solutions of achiral coumarin derivatives.

Probing molecular chirality by CD-sensitive dimeric metalloporphyrin hosts

This feature article reviews dimeric metalloporphyrin hosts employed as chirality probes in chiral recognition processes involving synthetic compounds and natural products. Upon formation of a chiral host-guest supramolecular complex between an achiral bis-metalloporphyrin derivative and a chiral non-racemic guest, a CD response occurs in the porphyrin spectral region, which is diagnostic of the guest's absolute configuration. Several bis-porphyrin hosts used in the stereochemical investigation of organic compounds are described and the scope of their application as chirality probes critically assessed. The review encompasses the description of structural features of the host-guest complexes, the nature of the chirality transfer mechanism and the practical application in solving stereochemical problems. In particular, with reference to the method based on bis-porphyrin tweezers, we describe recent advances based on the use of molecular modeling, which have broadened the applicability of the tweezer methodology and allowed extraction of deeper structural information contained in the experimental CD data.

Preparation of Chiral Polydiacetylene Film from Achiral Monomers Using Circularly Polarized Light

Abstract Formation of chiral polydiacetylene (PDA) film using circularly polarized light (CPL) was demonstrated for the first time. Commercially available achiral derivative of diacetylene was used to prepare the vacuum evaporated monomer film and it was polymerized using ultra-violet CPL. Chiral source was only CPL, and the irradiation of left- and right-CPL definitely yielded opposite chiral polymer.

Side‐Chain Modified Analogues of Histaprodifen: Asymmetric Synthesis and Histamine H1‐Receptor Activity.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Second-Harmonic Generation within the P212121 Space Group, in a Series of Chiral (Salicylaldiminato)tin Schiff Base Complexes

A series of 10 (2−11) new chiral (salicylaldiminato)tin Schiff base complexes obtained from the Schiff base condensation of 4-(diethylamino)salicylaldehyde and various amino acids, in the presence of diphenyltin oxide, is reported together with the parent achiral (1) derivative. Compounds 2−7 crystallize in the P212121 orthorhombic space group, and their quadratic nonlinear optical properties are investigated. At the molecular level, the derivatives possess similar electronic spectra (λmax ≈ 395 nm), and hence molecular hyperpolarizabilities (β), in relation to the same π-conjugated “push−pull” electronic structure. In the solid state, they exhibit efficiencies in second-harmonic generation (SHG) up to 8 times that of urea. The SHG intensities of chromophores 2−6 appear largely correlated with a simple “degree of chirality” (dχ) parameter, defined from the molecular geometries. The intriguing issue of a possible quantification of chirality by means of SHG measurement is addressed.

Main chain helical transformation induced through UV light in arylidene polymer

Arylidene polymers are showing a preferred main chain conformation in the solution phase when subjected to the circular dichorism (CD) analysis. Probably the first time a non-azo, achiral and acrylate derivative of arylidene compound when subjected to polymerization is oriented itself in a definite helical form. Ultraviolet (UV) light cross-linking of these polymers induces the main chain asymmetric transformation from one preferred conformation to another conformation. Concentration independent nature of the conformational change was observed and the CD spectrum showing a blue shift at 270 nm due to loss in the conjugation of the molecule upon irradiation with UV light.

Short Communication: An Unusually Crystalline Enolacetate

We report the first crystal structure of a simple achiral enolacetate derivative. We discuss its structural characteristics and also comment on its conformational preference. This crystalline enolacetate (derived from tetralone and isopropenyl acetate) crystallized in an orthorhombic space group, Pbca, with cell dimensions a 9.358(2),b10.078(2), c 20.938(4) A and Z 8. This unit cell was centrosymmetric and contained an equal number of both enantiomeric conformers. Manuscript received: 26 April 2001. Final version: 6 July 2001.

Photochromic chiral liquid-crystalline mixed formulations: A new class of materials for data recording and storage

~Submitted December 6, 1998!Opticheski”Zhurnal 66, 136–140 ~June 1999!This paper describes the phase behavior and optical properties of the mixed formulation of achiral 1-menthanone derivative as a photosensitive dopant and a cholesteric copolymer. It is shownthat the exposure of the planar-oriented films of the mixture to UV radiation considerablydecreases the wavelength of the selective reflection maximum owing to the E-Z isomerization ofthe dopant. The kinetics of photoisomerization of the cholesteric films of the mixture ismeasured at various temperatures. The mixed formulation prepared is a unique promising mediumfor colored data recording and storage. © 1999 The Optical Society of America.@S1070-9762~99!02106-5#

The cubic mesophase of analogous chiral and achiral hydrazine derivatives

The structures of the cubic mesophases of a chiral and an achiral hydrazine derivative have been investigated by means of X-ray diffraction experiments. As seen from the phase diagram of the binary system, both cubic phases are incompletely miscible which can be explained by the different space groups of the cubic lattices. In contrast to the isotropic liquid, the cubic phase of the chiral compound exhibits a considerable optical rotation indicating phase chirality.