Polycyclic Derivatives Research Articles

A Rh-Catalyzed Cycloisomerization/Diels-Alder Cascade Reaction of 1,5-Bisallenes for the Synthesis of Polycyclic Heterocycles.

A novel methodology to transform bisallenes into a variety of polycyclic derivatives employing rhodium(I) catalysis has been developed. This transformation encompasses an intramolecular Rh-catalyzed cycloisomerization of bisallenes 1 to deliver a reactive cycloheptadiene, which concomitantly undergoes a regioselective [4 + 2] cycloaddition with alkenes. A complete mechanistic study of this transformation has been undertaken including DFT calculations. Overall, the methodology presented here constitutes a new and straightforward entry to polycyclic dihydroazepine and dihydrooxepine derivatives employing catalytic methods.

Microwave-synthesised hydrothermal co-pyrolysis of oil palm empty fruit bunch with plastic wastes from Nigeria

Microwave-assisted hydrothermal co-pyrolysis of biomass (oil palm empty fruit bunch) and plastic waste from sachet-water (widely available in Nigeria) was studied to improve the yield and quality of bio-oil. The experiment was carried out in a customised microwave system under a maximum microwave power of 300 W, using a coconut shell-based susceptor. Further, the hydrothermal process was optimised using Box–Behnken design. The optimum conditions at which the highest bio-oil yield (66.7 wt%) was obtained were determined to be a temperature of about 380 °C, a sachet-water plastic ratio of 49 wt%, and a carrier gas flow rate of 1500 mL/min. Major chemical compounds found (by gas chromatography–mass spectrometry) in the aqueous phase of the bio-oil were alkane (decane), 3.7% and phenol, 84.9% with methoxyphenyl, 2.5% and ethanone, 8.9%. Aliphatic hydrocarbons (22.7%), monoaromatic (15.3%) and polycyclic (9.16%) aromatic hydrocarbons, linear oxygenates (2.1%), furan derivatives (2.3%), phenol derivatives (15.84%) and other compounds such as derivatives of cyclopentanones and pyran were found in the organic phase of the bio-oil which constituted 39.7% of the bio-oil fraction. Aqueous pre-treatment of the sample with deionised water under microwaves enhanced selectivity and produced bio-oil with optimum phenolic compounds (84.9%) in the aqueous bio-oil.

Synthesis, anti-tuberculosis activity and QSAR study of 2,4-diarylquinolines and analogous polycyclic derivatives

The multicomponent syntheses of 2,4-di-aryl-quinolines and analogous polycyclic derivatives as anti-tuberculosis agents were described. They were prepared via Beyer and Friedländer methods under microwave irradiation in short reaction times and good yields. Several homogeneous and heterogeneous acid catalysts were compared for preparing 2,4-di-arylquinolines and among them trifluoroacetic acid (TFA) reached the higher yields. Two derivatives exhibited activity against Mycobacterium tuberculosis H37Rv (Mtb), underwent additional testing and were considered lead compounds. The synthesis of a series of polycyclic analogous led to six new active compounds and a Quantitative Structure Activity Relationship study (QSAR) study was established.

Cascade Reactions of α‐Phenylcinnamic Acid to Polycyclic Compounds Promoted by High Valent Transition Metal Halides

Abstractα‐Phenylcinnamic acid converts into polycyclic derivatives by interaction with high valent transition metal halides in chloroform at reflux temperature. Different products, featured by local structural differences depending on the nature of the metal halide system (i. e. WCl6, PCl5/NbF5 or PCl5/NbCl5), are easily isolable after treatment with water. In particular, WCl6 configures as an efficient multitasking agent, working as 1) chlorinator of the carboxylic acid function, 2) catalytic precursor for intra‐ and intermolecular rearrangements, and 3) catalytic precursor for Baeyer‐Villiger lactonization in water at ambient temperature, exploiting air as oxidant. The products have been purified by alumina chromatography, and identified by analytical and spectroscopic (IR, NMR) techniques, and by single crystal X‐ray diffraction in three cases. Their formation probably involves a common reaction pathway which has been rationalized by DFT calculations.

Genetic Polymorphisms Associated with Environmental Exposure to Polycyclic Derivatives in African Children.

Background The nonracial leukopenia may be a result of exposure to polycyclic derivatives (benzene-toluene-xylene (BTX)) and may arise from a possible change in the bone marrow microenvironment. The present study sought to evaluate the association of genetic polymorphisms in xenobiotic-metabolizing enzymes with hematological and biochemical profiles. Methods We evaluated 89 African descendant children, exposed indirectly to benzene derivatives. Laboratory parameters were investigated by automated methods and genetic polymorphisms by PCR-RFLP and PCR multiplex. Results Children with leukopenia had significantly decreased white blood cells (WBCs) and platelet counts, which is not consistent with benign leukopenia. In the same group, we have found that carriers of the CYP2E1 variant allele had decreased WBC and lymphocytes. Those with NQO1 variant allele had decreased WBC, neutrophil, eosinophil, monocyte, and lymphocyte counts. Carriers of the MPO variant allele had decreased WBC, neutrophil, eosinophil, basophil, monocyte, lymphocyte, and platelet counts and an elevated free iron level. Children with GSTT and GSTM null exhibited decreased WBC, neutrophil, basophil, and lymphocyte counts. Our multivariate analysis model reveals that females were independently associated with leukopenia. Conclusion Our results suggest that the polymorphisms investigated were associated with hematological changes in the studied population. These alterations could be heightened by exposure to benzene derivatives.

Metal-catalyzed privileged 2- and 3-functionalized indole synthesis*

This review summarizes the metal-catalyzed approaches for the synthesis of privileged 2- and 3-functionalized indoles via the Fischer indole synthesis, cycloaddition reaction, C–H activation reaction, and coupling reactions. Polycyclic derivatives of indole are also listed including triptamine-based pharmaceutical 5-HT1D agonist L 775,606. Some important mechanism studies are described in details in this review. The review covers literature for the last 20 years.

Asymmetric Organocatalytic One-Pot, Two-Step Sequential Process to Synthesize Chiral Acetal-Containing Polycyclic Derivatives from Cyclic Hemiacetals and Enones.

We have developed an efficient one-pot, two-step sequential process to synthesize biologically and synthetically important chiral acetal-containing polycyclic derivatives. This novel protocol had been proved to proceed via Michael-lactolization-oxocarbenium ion ring-closing sequence, which was initiated by a key reactive enamine intermediate and interrupted the previously established reaction pathway of two different enones used in this work, and generated the corresponding cycloadducts with excellent stereoselectivity bearing up to seven continuous stereocenters. Both chiral and racemic starting cyclic hemiacetals worked well in this strategy. The synthetic applications of the obtained polycyclic products have also been demonstrated.

Formal (4+1) Cycloaddition and Enantioselective Michael–Henry Cascade Reactions To Synthesize Spiro[4,5]decanes and Spirooxindole Polycycles

AbstractSpiro[4,5]decanes and polycyclic compounds bearing spiro[4,5]decane systems are important biofunctional molecules. Described are diastereoselective formal (4+1) cycloaddition reactions to afford oxindole‐functionalized spiro[4,5]decanes and organocatalytic enantioselective Michael–Henry cascade reactions of the (4+1) cycloaddition products to generate spirooxindole polycyclic derivatives bearing the spiro[4,5]decane system. Spiro[4,5]decanes bearing oxindoles containing three stereogenic centers and spirooxindole polycycles having seven stereogenic centers, including two all‐carbon chiral quaternary centers and one tetrasubstituted chiral carbon center, were obtained with high diastereo‐ and enantioselectivities.

Formal (4+1) Cycloaddition and Enantioselective Michael-Henry Cascade Reactions To Synthesize Spiro[4,5]decanes and Spirooxindole Polycycles.

Spiro[4,5]decanes and polycyclic compounds bearing spiro[4,5]decane systems are important biofunctional molecules. Described are diastereoselective formal (4+1) cycloaddition reactions to afford oxindole-functionalized spiro[4,5]decanes and organocatalytic enantioselective Michael-Henry cascade reactions of the (4+1) cycloaddition products to generate spirooxindole polycyclic derivatives bearing the spiro[4,5]decane system. Spiro[4,5]decanes bearing oxindoles containing three stereogenic centers and spirooxindole polycycles having seven stereogenic centers, including two all-carbon chiral quaternary centers and one tetrasubstituted chiral carbon center, were obtained with high diastereo- and enantioselectivities.

N‐Heterocyclic Carbene/Potassium Ion Cooperatively Catalyzed Phenylation Reactions of α,β‐Unsaturated Acylazoliums

A catalytic phenylation reaction of α,β‐unsaturated acylazoliums with in‐situ‐generated phenolates was developed. A combination of N‐heterocyclic carbene and potassium ion cooperatively catalyzed the generation of α,β‐unsaturated acylazoliums and phenolates from α,β‐unsaturated phenolic esters for the efficient [3+3] annulation, which involves a dearomatization–rearomatization process. The approach gives good yields and excellent regioselectivities, and the products could be easily converted into high‐value polycyclic derivatives. Mechanistic studies demonstrated that the potassium ion plays a vital role in this reaction.

From Enynyl Esters to Functionalized Polycyclic Derivatives via Cycloisomerization and Post-Functionalization

The post-functionalization of ketone products originating from the PtCl2-catalyzed cycloisomerization of enynyl esters is described. Post-functionalization is accomplished via diastereoselective alkylation, regioselective cyclopropane opening and regioselective Baeyer–Villiger and Beckmann rearrangements to provide functionalized polycycles.

Photochemical cyclocondensation of 1-arylthio-2-azidoanthraquinones with phenols

Photolysis of 1-arylthio-2-azidoanthraquinones in DMSO in the presence of phenols leads to the formation of 5H-naphtho[2,3-c]phenothiazine-8,13-diones, in which the nitrogen atom is covalently bonded with the phenyl ring of the introduced phenol. As a result, poorly available polycyclic phenothiazine derivatives were obtained in one step in high yields. The cyclo-condensation with phenols was found to proceed only photochemically.

ChemInform Abstract: Sulfonyl Azoles in the Synthesis of 3‐Functionalized Azole Derivatives

AbstractReview: [111 refs.

Cyclic Opioid Peptides.

For decades the opioid receptors have been an attractive therapeutic target for the treatment of pain. Since the first discovery of enkephalin, approximately a dozen endogenous opioid peptides have been known to produce opioid activity and analgesia, but their therapeutics have been limited mainly due to low blood brain barrier penetration and poor resistance to proteolytic degradation. One versatile approach to overcome these drawbacks is the cyclization of linear peptides to cyclic peptides with constrained topographical structure. Compared to their linear parents, cyclic analogs exhibit better metabolic stability, lower offtarget toxicity, and improved bioavailability. Extensive structure-activity relationship studies have uncovered promising compounds for the treatment of pain as well as further elucidate structural elements required for selective opioid receptor activity. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic derivatives. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored. In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches to improve bioavailability are elaborated and concluded with a discourse towards polycyclic peptides.

Sulfonyl Azoles in the Synthesis of 3-Functionalized Azole Derivatives.

Sulfonyl indoles, as well as related azolyl derivatives, have been recently introduced in synthesis as stable precursors of reactive indolenine intermediates. This personal account reports on the discovery of sulfonyl azoles and their practical utilization in many synthetic processes for the preparation of functionalized 3-substituted indoles, indazoles, and pyrroles. The indolenine intermediates obtained by treatment of sulfonyl azoles with Brønsted bases or Lewis acids can be considered as vinylogous imino derivatives that can be made to react with different nucleophilic reagents. These include organometallic reagents, reducing agents, stabilized carbanions, and heteronucleophiles. The controlled and mild conditions for the generation of indolenines from sulfonyl azoles make these substrates particularly useful in asymmetric synthesis, exploiting organo- or metal-catalyzed processes. Although less exploited, sulfonyl indoles can also be involved in photochemical processes for the preparation of polycyclic derivatives.

Spectroscopic investigation, molecular interactions and molecular docking studies on 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Vibrational spectroscopy is an essential tool for the structural investigation of the organic molecules. Benzodiazepines and their polycyclic derivatives are chief class of bioactive compounds. They are frequently used as anticonvulsant, hypnotic, analgesic, anti-inflammatory and anti depressive agents. The alprazolam is a derivative of benzodiazepine. The IUPAC name of alprazolam is 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine. Its molecular formula is C17H13ClN4. Theoretical calculations are used to analyse the vibrational frequencies of alprazolam. The Fourier Transform infrared spectrum of the compound is recorded between 400–4000cm−1 in solid phase. The electronic properties like HOMO and LUMO energies are determined. Mulliken charges of the sample are determined along with NBO charges. The 13C and 1H NMR chemical shifts are calculated and compared with experimental values. Chemical shifts are reported in parts per million relative to tretramethylsilane. To study the biological activity of the investigation molecule, molecular docking (ligand-protein) stimulations are performed using the web server SWISSDOCK. The full fitness score, binding energy, delta G and hydrogen bond lengths values are determined.

Stabilization of non-standard conformations of the annulene rings in cyclobutadiene-framed [n]annulenes (n = 8, 10, 12, 14) and their beryllium sandwich-like complexes: a quantum chemical study

The structures of a series of polycyclic derivatives of [n]annulenes (n = 8, 10, 12, 14) functionalized with peripheral cyclobutadiene rings were studied using the DFT B3LYP/6-311+G(3df,2p) and M062X/6-311+G(3df,2p) methods. The compounds with n = 8 and 10 have the planar and those with n = 12, 14 saddle-shaped conformations of the central rings. Stabilization of non-standard planar forms of the hydrocarbons with central 12- and 14-membered conjugated rings may be achieved through π-complexation of C=C bonds of the cyclobutadiene fragments with beryllium atoms to afford the sandwich-like complexes with circular arrangement of beryllium centers around the perimeter of a ligand.

Substrate-Controlled, One-Pot Synthesis: Access to Chiral Chroman-2-one and Polycyclic Derivatives.

Based on the appropriate choice of electrophiles, one-pot, multicomponent, enantioselective domino reactions have been realized which contain a five-step sequence and provide highly efficient access to potentially bioactive chroman-2-one derivatives as a single diastereoisomer with excellent enantioselectivities and in high yields. This new strategy could significantly improve the previous protocol by directly starting from commercial 2-hydroxybenzaldehydes rather than preformed lactols, which have to be synthesized in several additional steps.

ChemInform Abstract: The Voight Reaction on Tertiary α‐Hydroxy Ketones.

AbstractThe Voight amination is applied for the synthesis of several tert‐α‐amino ketones present on various polycyclic derivatives like phenanthrene, pyrenes.

ChemInform Abstract: Enantioselective Synthesis of Pyrrole‐Based Spiro‐ and Polycyclic Derivatives by Iridium‐Catalyzed Asymmetric Allylic Dearomatization and Controllable Migration Reactions.

The first highly diastereo- and enantioselective synthesis of five-membered spiro-2H-pyrroles was achieved using an Ir-catalyzed asymmetric allylic dearomatization reaction. The spiro-2H-pyrrole derivatives readily undergo a controllable and stereospecific allylic migration under acid catalysis, providing polycyclic pyrrole derivatives in excellent yields and ee values. Additionally, the novel Ir-complex K1, derived from [Ir(cod)Cl]2 (cod=1,5-cyclooctadiene) and N-benzhydryl-N-phenyldinaphthophosphoramidite (BHPphos), showed excellent control of both diastereo- and enantioselectivities.