Cyclopentene Moiety Research Articles

Proximity Effects and Aggregation of Hamilton-Receptor Barbiturate Host-Guest Complexes Probed by Cross-Metathesis and ESI MS Analysis.

The molecular environment around supramolecular bonding systems significantly affects their stability and the assembly of host-guest complexes, most prominent for hydrogen bonds (H-bonds). Hamilton receptor-barbiturate host-guest complexes are well-known in solution, typically forming a 1:1 molar ratio complex. However, within a polymer matrix, these complexes can form higher-order assemblies, deviating from the standard 1:1 complex, which are challenging to characterize and often require lab-intensive methods. In this study, a novel Hamilton receptor (H) was equipped with cyclopentene moieties and used as a host to form host-guest complexes (H-B) with allobarbital (B), followed by covalent crosslinking. UV-Vis spectroscopy titration experiments in different solvents and at various temperatures revealed that polar solvents containing additional H-bonding sites significantly reduce the formation of the 1:1 H-B complex, as indicated by a reduced association constant. Higher-order aggregates (HH-dimer, HHH-trimer) were subsequently detected via an alkene cross-metathesis (CM) reaction to fix the assemblies covalently, followed by analysis via electrospray ionization mass spectrometry (ESI MS). This two-step method, firstly via CM fixation followed by ESI MS, was extended to study the H-B model complex within a polyisobutylene (PIB) matrix, presenting a direct method to analyze the complex host-guest assembly in solvent-free (polymer) environments.

Enantioselective Preparation of Cyclopentene-Based Amino Acids with a Quaternary Carbon Center.

Azlactone is an important starting material for synthesizing amino acids containing a quaternary α-carbon. In this study, we have developed a sequential "one-pot" procedure involving an enantioselective spirocyclization reaction followed by acidic azlactone opening, which led to amino acid derivatives. The key step of this procedure is a spirocyclization between propargylated azlactones and enals by using a cooperative catalytic approach that combines chiral secondary amine and achiral Pd(0) complexes. The final acid opening of the azlactone motif allows isolation of the corresponding amino acid derivatives as major diastereoisomers in yields ranging from 37% to 70% with enantioselectivities of 85-97% ee. These synthesized amino acid derivatives hold great potential in the pharmaceutical and bioactive compound industries. Moreover, the final amino acid products with a cyclopentene moiety can be further derivatized, opening up even more possibilities for their application.

Deviated binding of anti-HBV nucleoside analog E-CFCP-TP to the reverse transcriptase active site attenuates the effect of drug-resistant mutations

While certain human hepatitis B virus-targeting nucleoside analogs (NAs) serve as crucial anti-HBV drugs, HBV yet remains to be a major global health threat. E-CFCP is a 4′-modified and fluoromethylenated NA that exhibits potent antiviral activity against both wild-type and drug-resistant HBVs but less potent against human immunodeficiency virus type-1 (HIV-1). Here, we show that HIV-1 with HBV-associated amino acid substitutions introduced into the RT’s dNTP-binding site (N-site) is highly susceptible to E-CFCP. We determined the X-ray structures of HBV-associated HIV-1 RT mutants complexed with DNA:E-CFCP-triphosphate (E-CFCP-TP). The structures revealed that exocyclic fluoromethylene pushes the Met184 sidechain backward, and the resultant enlarged hydrophobic pocket accommodates both the fluoromethylene and 4′-cyano moiety of E-CFCP. Structural comparison with the DNA:dGTP/entecavir-triphosphate complex also indicated that the cyclopentene moiety of the bound E-CFCP-TP is slightly skewed and deviated. This positioning partly corresponds to that of the bound dNTP observed in the HIV-1 RT mutant with drug-resistant mutations F160M/M184V, resulting in the attenuation of the structural effects of F160M/M184V substitutions. These results expand our knowledge of the interactions between NAs and the RT N-site and should help further design antiviral NAs against both HIV-1 and HBV.

Designing Degradable Polymers from Tricycloalkenes via Complete Cascade Metathesis Polymerization

AbstractCascade metathesis polymerization has been developed as a promising method to synthesize complex but well‐defined polymers from monomers containing multiple reactive functional groups. However, this approach has been limited to the monomers involving simple alkene/alkyne moieties or produced mainly non‐degradable polymers. In this study, we demonstrate a complete cascade ring‐opening/ring‐closing metathesis polymerization (RORCMP) using various tricycloalkenes and two strategies for the efficient degradation. Through rational design of tricycloalkene monomers, the structure and reactivity relationship was explored. For example, tricycloalkenes with trans configuration in the central ring enabled faster and better selective cascade RORCMP than the corresponding cis isomers. Also, a 4‐substituted cyclopentene moiety in the monomers significantly enhanced the overall cascade RORCMP performance, with the maximum turnover number (TON) reaching almost 10,000 and molecular weight up to 170 kg/mol using an amide‐containing monomer. Furthermore, we achieved one‐shot cascade multiple olefin metathesis polymerization using tricycloalkenes and a diacrylate, to produce new highly A,B‐alternating copolymers with full degradability. Lastly, we successfully designed xylose‐based tricycloalkenes to give well‐defined polymers that underwent ultra‐fast and complete degradation under mild conditions.

Designing Degradable Polymers from Tricycloalkenes via Complete Cascade Metathesis Polymerization.

Cascade metathesis polymerization has been developed as a promising method to synthesize complex but well-defined polymers from monomers containing multiple reactive functional groups. However, this approach has been limited to the monomers involving simple alkene/alkyne moieties or produced mainly non-degradable polymers. In this study, we demonstrate a complete cascade ring-opening/ring-closing metathesis polymerization (RORCMP) using various tricycloalkenes and two strategies for the efficient degradation. Through rational design of tricycloalkene monomers, the structure and reactivity relationship was explored. For example, tricycloalkenes with trans configuration in the central ring enabled faster and better selective cascade RORCMP than the corresponding cis isomers. Also, a 4-substituted cyclopentene moiety in the monomers significantly enhanced the overall cascade RORCMP performance, with the maximum turnover number (TON) reaching almost 10,000 and molecular weight up to 170 kg/mol using an amide-containing monomer. Furthermore, we achieved one-shot cascade multiple olefin metathesis polymerization using tricycloalkenes and a diacrylate, to produce new highly A,B-alternating copolymers with full degradability. Lastly, we successfully designed xylose-based tricycloalkenes to give well-defined polymers that underwent ultra-fast and complete degradation under mild conditions.

Photoresponsive thiourea and urea catalysts for ring‐opening polymerization of L‐lactide

AbstractStimulus responsive catalysts have received increasing attention. Photoresponsive catalytic polymerization is particularly attractive because the noninvasive and versatile nature of light. Most photoresponsive ROP catalytic systems exhibit low activities, allowing ROP to be completed within several hours to 10 h. In this contribution, a series of (thio)ureas bearing dithienylcyclopentene optical molecular switch moiety are designed, synthesized, and characterized. The photoresponsive effects in (thio)urea/alkoxide mediated ROP of L‐lactide are investigated. These catalysts allow the ROP reactions of L‐lactide to be completed within a few minutes to 1 h and the resulting polyesters have narrow molecular weight distributions. The dithienylcyclopentene moiety allows photoisomerization to be completed within 1 min. The catalytic activity of the ROP catalyst can be altered by the photoisomerization of the dithienyl cyclopentene moiety by exposure to ultraviolet or visible light, respectively.

NIR‐Sensitized Activated Photoreaction between Cyanines and Oxime Esters: Free‐Radical Photopolymerization

AbstractCyanines comprising either a benzo[e]‐ or benzo[c,d]indolium core facilitate initiation of radical photopolymerization combined with high power NIR‐LED prototypes emitting at 805 nm, 860 nm, or 870 nm, while different oxime esters function as radical coinitiators. Radical photopolymerization followed an initiation mechanism based on the participation of excited states, requiring additional thermal energy to overcome an existing intrinsic activation barrier. Heat released by nonradiative deactivation of the sensitizer favored the system, even under conditions where a thermally activated photoinduced electron transfer controls the reaction protocol. The heat generated internally by the NIR sensitizer promotes generation of the initiating reactive radicals. Sensitizers with a barbiturate group at the meso‐position preferred to bleach directly, while sensitizers carrying a cyclopentene moiety unexpectedly initiated the photosensitized mechanism.

NIR‐Sensitized Activated Photoreaction between Cyanines and Oxime Esters: Free‐Radical Photopolymerization

Cyanines comprising either a benzo[e]‐ or benzo[c,d]indolium core facilitate initiation of radical photopolymerization combined with high power NIR‐LED prototypes emitting at 805 nm, 860 nm, or 870 nm, while different oxime esters function as radical coinitiators. Radical photopolymerization followed an initiation mechanism based on the participation of excited states, requiring additional thermal energy to overcome an existing intrinsic activation barrier. Heat released by nonradiative deactivation of the sensitizer favored the system, even under conditions where a thermally activated photoinduced electron transfer controls the reaction protocol. The heat generated internally by the NIR sensitizer promotes generation of the initiating reactive radicals. Sensitizers with a barbiturate group at the meso‐position preferred to bleach directly, while sensitizers carrying a cyclopentene moiety unexpectedly initiated the photosensitized mechanism.

Palladium-catalyzed allylic substitution between C-based nucleophiles and 6-azabicyclo[3.1.0]-hex-3-en-2-oxy derivatives: A new selectivity paradigm

Abstract The reaction between α-hydroxy-(or α-acetoxy) cyclopenten-aziridines (6-azabicyclo[3.1.0]hex-3-en-2-ols or acetates) and C-based nucleophiles in the presence of Pd(0)-catalysis was investigated. In all the cases studied, the reaction was totally regio- and diastereo-selective, affording a single adduct in moderate to good yields. Specifically, attack of the nucleophile at position 3 of the cyclopentene moiety, anti to the vicinal oxy group, with vinylogous ring opening of the aziridine ring, was observed. When the carbon acid is a very acidic methylene (pKa (DMSO) ≤ 7.3), the resulting adduct is a zwitterion, resulting from an intramolecular proton transfer between the amino group and the carbon acid moiety taking place after the C–C bond formation. A plausible mechanism for this transformation is put forward.

Fluorinated Phenanthrenes as Aryne Precursors: PAH Synthesis Based on Domino Ring Assembly Using 1,1-Difluoroallenes.

On treatment with the catalyst InBr3 , 1,1-difluoroallenes that bear a cyclopentene moiety and an aryl group underwent domino ring assembly in the presence or absence of N-bromosuccinimide or N-iodosuccinimide to afford aryne precursors such as three-ringed ortho-fluoro(halo)phenanthrenes, four-ringed ortho-fluoro(halo)tetraphenes, ortho-fluoro(halo)chrysenes and fluoro[4]helicenes. Metalation of the aryne precursors followed by elimination of the fluoride resulted in the unprecedented systematic generation of arynes bearing π-extended systems. Diels-Alder reactions of these arynes with isobenzofurans afforded the corresponding cycloadducts whose reductive aromatisation in an SnCl2 /HBr system furnished fully aromatised benzotriphenylenes. In addition, oxidative aryl-aryl coupling (the Scholl reaction) of these benzotriphenylenes facilitated the synthesis of 'half HBCs' (hexabenzocoronenes).

New High-Power LEDs Open Photochemistry for Near-Infrared-Sensitized Radical and Cationic Photopolymerization.

Cyanines derived from heptamethines were investigated in combination with iodonium salts as initiators of the radical polymerization of tripropylene glycol diacrylate and epoxides derived from bisphenol-A-diglycidylether. A new near-infrared (NIR) LED prototype emitting at 805 nm with an exposure intensity of 1.2 W cm-2 facilitated initiation of both radical and cationic polymerization using sensitizers derived from cyanines. This new light-emitting device has brought new insight into the photochemistry of cyanines with the general structure 1 because a combination of photonic and thermal processes strongly influences reaction pathways. In particular, cationic cyanines comprising a cyclopentene moiety and diphenylamino group in the center initiated the cationic polymerization of epoxides. Selective oxidation of this unit explains why specifically these derivatives may function as initiators for cationic polymerization. In contrast, when the diphenylamino group was replaced by a barbital group at the meso-position cationic polymerization of epoxides was not initiated.

Unusual Superior Activity of the First Generation Grubbs Catalyst in Cascade Olefin Metathesis Polymerization.

Recently, we reported a new cascade ring-opening/closing metathesis polymerization of monomers containing two cyclopentene moieties. Several Ru catalysts were tested, but the best polymerization results were unexpectedly obtained using the first-generation Grubbs catalyst (G1). This was puzzling since the second- and third-generation Grubbs catalysts are well-known for their higher activities compared to G1. In order to explain the unique and superior activity of G1, we conducted a series of kinetics experiments for the polymerization of 3,3'-oxydicyclopent-1-ene, a representative monomer of this cascade polymerization, as well as the competition polymerization with cycloheptene using the various Grubbs catalysts. Based on our results, we propose a model in which the differences in the steric hindrance between the different ligands and the monomer determine the selectivity of the catalyst approach to the monomer and, therefore, the extent to which the productive pathway leads to successful cascade polymerization. In short, G1 with the smaller ligand showed a high preference for the productive pathway.

Lewis Acid Promoted Regioselective Double Hydro(hetero)arylation of 6,6′‐Dialkyl‐Substituted Pentafulvenes: A Facile Approach to Bisindole Derivatives

A Lewis acid catalyzed double hydro(hetero)arylation of alkyl‐substituted pentafulvenes for the synthesis of bisindole‐substituted cyclopentenoids has been developed. The scope of the reaction was explored with a wide range of indoles and pentafulvenes, and mechanistic insights were obtained. In addition, we have also demonstrated a hydro(hetero)arylation–dehydroxylation reaction of 2‐hydroxy‐substituted pentafulvenes to afford bisindole derivatives with isoprenyl‐substituted cyclopentene moieties.

Facile Synthesis of Polycyclic Aromatic Hydrocarbons: Brønsted Acid Catalyzed Dehydrative Cycloaromatization of Carbonyl Compounds in 1,1,1,3,3,3‐Hexafluoropropan‐2‐ol

The cycloaromatization of aromatic aldehydes and ketones was readily achieved by using a Brønsted acid catalyst in 1,1,1,3,3,3‐hexafluoropropan‐2‐ol (HFIP). In the presence of a catalytic amount of trifluoromethanesulfonic acid, biaryl‐2‐ylacetaldehydes and 2‐benzylbenzaldehydes underwent sequential intramolecular cationic cyclization and dehydration to afford phenacenes and acenes, respectively. Furthermore, biaryl‐2‐ylacetaldehydes bearing a cyclopentene moiety at the α‐position underwent unprecedented cycloaromatization including ring expansion to afford triphenylenes. HFIP effectively promoted the cyclizations by suppressing side reactions presumably as a result of stabilization of the cationic intermediates.

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene.

Do not rely on the widely accepted rule that vicinal, sp3-positioned protons in cyclopentene moieties should always have more positive 3J NMR coupling constants for the cis than for the trans arrangement: Unrecognized exceptions might misguide one to wrong stereochemical assignments and thence to erroneous mechanistic conclusions. We show here that two structurally innocent-looking 2,3-dibromo-1,1-dimethylindanes violate the rule by means of their values of 3J(cis) = 6.1 Hz and 3J(trans) = 8.4 Hz. The stereoselective formation of the trans diastereomer from 1,1-dimethylindene was improved with the tribromide anion (Br3−) as the brominating agent in place of elemental bromine; the ensuing, regiospecific HBr elimination afforded 3-bromo-1,1-dimethylindene. The addition of elemental bromine to the latter compound, followed by thermal HBr elimination, furnished 2,3-dibromo-1,1-dimethylindene, whose Br/Li interchange reaction, precipitation, and subsequent protolysis yielded only 2-bromo-1,1-dimethylindene.

Synthesis of 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene Derivatives and Evaluations of Their Carbonic Anhydrase Isoenzymes Inhibitory Effects.

Rearrangement of 1,6-bis(3,4-dimethoxyphenyl)hexane-1,6-dione (8) gave two isomeric products having cyclopentene moiety. Starting from the major product (3,4-dimethoxyphenyl)[2-(3,4-dimethoxyphenyl)cyclopent-1-en-1-yl]methanone (11), eight new compounds (16-23) were obtained by the reactions such as reduction (by catalytic hydrogenation and NaBH4 ), nitration, 1,4-addition, bromination, and esterification reactions. Carbonic anhydrases (CA, E.C.4.2.1.1) are ubiquitous metalloenzymes present in almost all living organism that catalyze a simple reaction, the conversion of carbon dioxide (CO2 ) and water (H2 O) to bicarbonate ion (HCO3 (-) ) and a proton (H(+) ). CA isoenzymes I and II (hCA I and II) inhibition effects of synthesized eleven new and four known compounds (8-13 and 15-23) were investigated. Inhibition studies of the hCA I and II with 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene derivatives revealed that they possess effective inhibitory potency. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized 4-[2-(3,4-dimethoxybenzyl)cyclopentyl]-1,2-dimethoxybenzene derivatives with Ki s in the range of 313.16-1537.00 nm against hCA I and in the range of 228.31-1927.31 nm against hCA II, respectively.

Luminescent neutral lanthanide complexes of 5-aryl-2,2′-bipyridine-6-carboxylic acids, synthesis and properties

Luminescent lanthanide complexes of 4-aryl-1-(2-pyridyl)-6,7-dihydro-5H-cyclopenta[c]pyridine-3-carboxylic acids and 5-tolyl-2,2′-bipyridine-6-carboxylic acid were prepared. The ligands were synthesized using the “1,2,4-triazine” methodology. In one case, the opportunity of copper complex preparation, followed by exchange of the metal cation from copper to europium to overcome synthetic difficulties, was demonstrated. The ability of tuning the properties of the complexes by means of varying the structure of the ligands was demonstrated. In particular, the introduction of the cyclopentene moiety allowed the preparation of highly soluble complexes in non-polar organic solvents.

Multiple Olefin Metathesis Polymerization That Combines All Three Olefin Metathesis Transformations: Ring-Opening, Ring-Closing, and Cross Metathesis.

We demonstrated tandem ring-opening/ring-closing metathesis (RO/RCM) polymerization of monomers containing two cyclopentene moieties and postmodification via insertion polymerization. In this system, well-defined polymers were efficiently formed by tandem cascade RO/RCM reaction pathway. Furthermore, these polymers could be transformed to new A,B-alternating copolymers via a sequential cross metathesis reaction with a diacrylate. Additionally, we demonstrated the concept of multiple olefin metathesis polymerization in which the dicyclopentene and diacrylate monomers underwent all three olefin metathesis transformations (ring-opening, ring-closing, and cross metathesis) in one shot to produce A,B-alternating copolymer.

One-Pot Synthesis of Novel Cyclopentene-Fused Octahydropyridoquinolines and Octahydrophenanthrolines

New cyclopentene-fused octahydropyridoquinolines and octahydrophenanthrolines were prepared by a stereoselective three-component cyclocondensation of benzene-1,4-diamine, cyclopenta-1,3-diene, and an aromatic aldehyde. Single-crystal X-ray diffraction data provided evidence for the formation of cyclopentene-fused octahydropyridoquinolines and octahydrophenanthrolines with a syn -planar arrangement of the cyclopentene rings. The cyclocondensation of benzene-1,4-diamine, cyclopenta-1,3-diene, and formaldehyde gave new type of polycyclic compound containing four cyclopentene moieties oriented in a mutually antiplanar manner.

Domino Synthesis of Fluorine‐Substituted Polycyclic Aromatic Hydrocarbons: 1,1‐Difluoroallenes as Synthetic Platforms

Rather crafty: 1,1-Difluoroallenes bearing an aryl group and a cyclopentene moiety undergo indium(III)-catalyzed Friedel-Crafts-type cyclization with subsequent ring expansion and dehydrogenation to afford fluorinated polycyclic aromatic hydrocarbons in high yields. The introduction of an Ar group was effected by in situ halogenation of the intermediary indium species and a subsequent Suzuki-Miyaura reaction.