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Clinical Cardiology Dec 2021
Topics: Alkynes; Benzoxazines; Cyclopropanes; HIV Infections; Humans
PubMed: 34694012
DOI: 10.1002/clc.23745 -
Journal of the American Chemical Society May 2022The hexadehydro-Diels-Alder (HDDA) reaction converts a 1,3-diyne bearing a tethered alkyne (the diynophile) into bicyclic benzyne intermediates upon thermal activation....
The hexadehydro-Diels-Alder (HDDA) reaction converts a 1,3-diyne bearing a tethered alkyne (the diynophile) into bicyclic benzyne intermediates upon thermal activation. With only a few exceptions, this unimolecular cycloisomerization requires, depending on the nature of the atoms connecting the diyne and diynophile, reaction temperatures of 80-130 °C to achieve a convenient half-life (, 1-10 h) for the reaction. In this report, we divulge a new variant of the HDDA process in which the tether contains a central, quaternized nitrogen atom. This construct significantly lowers the activation barrier for the HDDA cycloisomerization to the benzyne. Moreover, many of the ammonium ion-based, alkyne-containing substrates can be spontaneously assembled, cyclized to benzyne, and trapped in a single-vessel, ambient-temperature operation. DFT calculations provide insights into the origin of the enhanced rate of benzyne formation.
Topics: Alkynes; Ammonium Compounds; Cycloaddition Reaction; Diynes; Temperature
PubMed: 35442671
DOI: 10.1021/jacs.2c00877 -
Nature Communications Jun 2022Chiral organoborons are of great value in asymmetric synthesis, functional materials, and medicinal chemistry. The development of chiral bis(boryl) alkanes, especially...
Chiral organoborons are of great value in asymmetric synthesis, functional materials, and medicinal chemistry. The development of chiral bis(boryl) alkanes, especially optically enriched 1,1-diboron compounds, has been greatly inhibited by the lack of direct synthetic protocols. Therefore, it is very challenging to develop a simple and effective strategy to obtain chiral 1,1-diborylalkanes. Herein, we develop an enantioselective copper-catalyzed cascade double hydroboration of terminal alkynes and highly enantioenriched gem-diborylalkanes were readily obtained. Our strategy uses simple terminal alkynes and two different boranes to construct valuable chiral gem-bis(boryl) alkanes with one catalytic and one ligand pattern, which represents the simplest and most straightforward strategy for constructing such chiral gem-diborons.
Topics: Alkanes; Alkynes; Catalysis; Copper; Stereoisomerism
PubMed: 35725731
DOI: 10.1038/s41467-022-31234-2 -
Organic Letters Jun 2021Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore,...
Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore, methods for synthesizing azoheteroarenes are highly desirable. Here, we utilize azide-alkyne click chemistry to access arylazo-1,2,3-triazoles, a previously unexplored class of azoheteroarenes that exhibit high thermal stabilities and near-quantitative bidirectional photoconversion. Controlling the catalyst or 1,3-dipole grants access to both regioisomeric arylazotriazoles and arylazoisoxazoles, highlighting the versatility of our approach.
Topics: Alkynes; Azides; Azo Compounds; Catalysis; Click Chemistry; Molecular Structure; Triazoles
PubMed: 34019429
DOI: 10.1021/acs.orglett.1c01230 -
The Journal of Organic Chemistry Aug 2021The mechanism of the Kinugasa reaction, that is, the copper-catalyzed formation of β-lactams from nitrones and terminal alkynes, is re-evaluated by means of density...
The mechanism of the Kinugasa reaction, that is, the copper-catalyzed formation of β-lactams from nitrones and terminal alkynes, is re-evaluated by means of density functional theory calculations and in light of recent experimental findings. Different possible mechanistic scenarios are investigated using phenanthroline as a ligand and triethylamine as a base. The calculations confirm that after an initial two-step cycloaddition promoted by two copper ions, the resulting five-membered ring intermediate can undergo a fast and irreversible cycloreversion to generate an imine and a dicopper-ketenyl intermediate. From there, the reaction can proceed through a nucleophilic attack of a ketenyl copper intermediate on the imine and an intramolecular cyclization, rather than through the previously suggested (2 + 2) Staudinger synthesis.
Topics: Alkynes; Copper; Cyclization; Cycloaddition Reaction; Imines
PubMed: 34255506
DOI: 10.1021/acs.joc.1c01351 -
Organic Letters Jan 2023A novel class of stable monoareno-pentalenes is introduced that have an olefinic proton on each five-membered ring of the pentalene subunit. Their synthesis was...
A novel class of stable monoareno-pentalenes is introduced that have an olefinic proton on each five-membered ring of the pentalene subunit. Their synthesis was accomplished via a regioselective carbopalladation cascade reaction between -arylacetyleno -dibromoolefins and TIPS-acetylene. These molecules could be experimental probes of magnetic (anti)aromaticity effects.
Topics: Protons; Molecular Structure; Alkenes; Acetylene
PubMed: 36576234
DOI: 10.1021/acs.orglett.2c03752 -
Journal of the American Chemical Society Aug 2022An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling...
An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the coupling products are formed with excellent regio-, diastereo-, and enantioselectivities, and the protocol is functional group tolerant. Moreover, we report conditions that allow the reaction to proceed with complete reversal of diastereoselectivity. Mechanistic studies are consistent with an unprecedented dual role for the iridium catalyst, enabling the propargylic deprotonation of the alkyne through π-coordination, as well as the generation of a π-allyl species from the allylic ether starting material.
Topics: Alkynes; Allyl Compounds; Catalysis; Ethers; Iridium; Stereoisomerism
PubMed: 35976157
DOI: 10.1021/jacs.2c07297 -
Polimery W Medycynie 2022Black pepper (Piper nigrum L.) is a climbing perennial plant in the Piperaceae family. Pepper has been known since antiquity for its use both as a medicine and a spice.... (Review)
Review
Black pepper (Piper nigrum L.) is a climbing perennial plant in the Piperaceae family. Pepper has been known since antiquity for its use both as a medicine and a spice. It is particularly valued for its pungency attributed to its principal constituent - piperine. This review summarizes the information on the biological source of piperine, its extraction and isolation strategies, physicochemical properties, and pharmacological activity - analgesic, immunomodulatory, anti-depressive, anti-diarrheal, hepatoprotective, etc. The effect of piperine on biotransformation of co-administered drugs is also presented in this review, along with the mechanisms involved in its bioavailability-enhancing effect. Its important medicinal uses, including anti-hepatotoxic, anti-diarrheal, anti-depressive, analgesic, and immunomodulatory effects, besides many other traditional uses, are compiled. Based on an exhaustive review of literature, it may be concluded that piperine is a very promising alkaloid found in members of the Piperaceae family.
Topics: Alkaloids; Benzodioxoles; Piper nigrum; Piperidines; Polyunsaturated Alkamides
PubMed: 35196422
DOI: 10.17219/pim/145512 -
Current Opinion in Chemical Biology Apr 2020One of the challenges of modern inorganic chemistry is translating the potential of metal catalysts to living systems to achieve controlled non-natural transformations.... (Review)
Review
One of the challenges of modern inorganic chemistry is translating the potential of metal catalysts to living systems to achieve controlled non-natural transformations. This field poses numerous issues associated with the metal compounds biocompatibility, stability, and reactivity in complex aqueous environment. Moreover, it should be noted that although referring to 'metal catalysis', turnover has not yet been fully demonstrated in most of the examples within living systems. Nevertheless, transition metal catalysts offer an opportunity of modulating bioprocesses through reactions that are complementary to enzymes. In this context, gold complexes, both coordination and organometallic, have emerged as promising tools for bio-orthogonal transformations, endowed with excellent reactivity and selectivity, compatibility within aqueous reaction medium, fast kinetics of ligand exchange reactions, and mild reaction conditions. Thus, a number of examples of gold-templated reactions in a biologically relevant context will be presented and discussed here in relation to their potential applications in biological and medicinal chemistry.
Topics: Alkynes; Animals; Catalysis; Coordination Complexes; Cycloaddition Reaction; Fluorescent Dyes; Gold; Humans; Hydrogenation; Kinetics; Ligands; Optical Imaging; Oxidation-Reduction; Pargyline; Propylamines; Rhodamines; Substrate Specificity
PubMed: 32086166
DOI: 10.1016/j.cbpa.2019.12.007 -
Journal of Acquired Immune Deficiency... Dec 2020Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for the treatment of HIV-1 infection in patients with no known DOR... (Review)
Review
BACKGROUND
Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for the treatment of HIV-1 infection in patients with no known DOR resistance-associated mutations. DOR was rationally designed to address limitations associated with other approved NNRTIs, particularly resistance from common NNRTI resistance-associated mutants containing K103N, Y181C, or G190A reverse transcriptase substitutions.
SETTING
Data to date from both in vitro studies and clinical trials have been compiled to summarize the resistance profile of DOR.
METHODS
We analyzed data from in vitro studies and phase 2 and 3 trials to assess the emergence of resistance-associated mutations and their impact on efficacy among participants treated with DOR.
RESULTS
DOR exhibited a distinct resistance profile compared with efavirenz and rilpivirine in vitro and in vivo; mutant viruses that were resistant to DOR showed limited cross-resistance to efavirenz and rilpivirine. In clinical trials, the development of DOR resistance-associated substitutions in reverse transcriptase was uncommon.
CONCLUSION
Overall, minimal cross-resistance across NNRTIs was observed for DOR and limited development of DOR-related resistance. These data should assist clinicians in further understanding the resistance profile of DOR, so appropriate treatment decisions can be made for their patients.
Topics: Alkynes; Anti-HIV Agents; Benzoxazines; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cyclopropanes; Drug Resistance, Viral; HIV Infections; HIV-1; Humans; In Vitro Techniques; Pyridones; Rilpivirine; Triazoles
PubMed: 32925358
DOI: 10.1097/QAI.0000000000002496