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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 -
Molecules (Basel, Switzerland) Sep 2018Recent progress in the leading synthetic applications of acetylene is discussed from the prospect of rapid development and novel opportunities. A diversity of reactions... (Review)
Review
Recent progress in the leading synthetic applications of acetylene is discussed from the prospect of rapid development and novel opportunities. A diversity of reactions involving the acetylene molecule to carry out vinylation processes, cross-coupling reactions, synthesis of substituted alkynes, preparation of heterocycles and the construction of a number of functionalized molecules with different levels of molecular complexity were recently studied. Of particular importance is the utilization of acetylene in the synthesis of pharmaceutical substances and drugs. The increasing interest in acetylene and its involvement in organic transformations highlights a fascinating renaissance of this simplest alkyne molecule.
Topics: Acetylene; Alkynes; Drug Design; Molecular Structure; Pharmaceutical Preparations
PubMed: 30250005
DOI: 10.3390/molecules23102442 -
Molecules (Basel, Switzerland) Mar 2019The high energy packed in alkyne functional group makes alkyne reactions highly thermodynamically favorable and generally irreversible. Furthermore, the presence of two... (Review)
Review
The high energy packed in alkyne functional group makes alkyne reactions highly thermodynamically favorable and generally irreversible. Furthermore, the presence of two orthogonal π-bonds that can be manipulated separately enables flexible synthetic cascades stemming from alkynes. Behind these "obvious" traits, there are other more subtle, often concealed aspects of this functional group's appeal. This review is focused on yet another interesting but underappreciated alkyne feature: the fact that the CC alkyne unit has the same oxidation state as the -CH2C(O)- unit of a typical carbonyl compound. Thus, "classic carbonyl chemistry" can be accessed through alkynes, and new transformations can be engineered by unmasking the hidden carbonyl nature of alkynes. The goal of this review is to illustrate the advantages of using alkynes as an entry point to carbonyl reactions while highlighting reports from the literature where, sometimes without full appreciation, the concept of using alkynes as a hidden entry into carbonyl chemistry has been applied.
Topics: Aldehydes; Alkynes; Catalysis; Cyclization; Ketones; Molecular Structure; Stereoisomerism
PubMed: 30875972
DOI: 10.3390/molecules24061036 -
Chemical Society Reviews Apr 2010The advent of click chemistry has led to an influx of new ideas in the nucleic acids field. The copper catalysed alkyne-azide cycloaddition (CuAAC) reaction is the... (Review)
Review
The advent of click chemistry has led to an influx of new ideas in the nucleic acids field. The copper catalysed alkyne-azide cycloaddition (CuAAC) reaction is the method of choice for DNA click chemistry due to its remarkable efficiency. It has been used to label oligonucleotides with fluorescent dyes, sugars, peptides and other reporter groups, to cyclise DNA, to synthesise DNA catenanes, to join oligonucleotides to PNA, and to produce analogues of DNA with modified nucleobases and backbones. In this critical review we describe some of the pioneering work that has been carried out in this area (78 references).
Topics: Alkynes; Azides; Catalysis; Copper; Cyclization; DNA; Oligonucleotides; Peptide Nucleic Acids
PubMed: 20309492
DOI: 10.1039/b901971p -
Marine Drugs Nov 2016Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic peptides have been identified from marine organisms, especially cyanobacteria and marine... (Review)
Review
Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic peptides have been identified from marine organisms, especially cyanobacteria and marine mollusks. This review has presented 66 peptides, which covers over 90% marine peptides with terminal alkynyl fatty acyl units. In fact, more than 90% of these peptides described in the literature are of cyanobacterial origin. Interestingly, all the linear peptides featured with terminal alkyne were solely discovered from marine cyanobacteria. The objective of this article is to provide an overview on the types, structural characterization of these unusual terminal alkynyl fatty acyl units, as well as the sources and biological functions of their composed peptides. Many of these peptides have a variety of biological activities, including antitumor, antibacterial, antimalarial, etc. Further, we have also discussed the evident biosynthetic origin responsible for formation of terminal alkynes of natural PKS (polyketide synthase)/NRPS (nonribosome peptide synthetase) hybrids.
Topics: Alkynes; Aquatic Organisms; Biological Products; Cyanobacteria; Humans; Peptide Synthases; Peptides; Polyketide Synthases
PubMed: 27886049
DOI: 10.3390/md14110216 -
Angewandte Chemie (International Ed. in... Feb 2021By using Rh-H catalysis, we couple α-nitroesters and alkynes to prepare α-amino-acid precursors. This atom-economical strategy generates two contiguous stereocenters,...
By using Rh-H catalysis, we couple α-nitroesters and alkynes to prepare α-amino-acid precursors. This atom-economical strategy generates two contiguous stereocenters, with high enantio- and diastereocontrol. In this transformation, the alkyne undergoes isomerization to generate a Rh -π-allyl electrophile, which is trapped by an α-nitroester nucleophile. A subsequent reduction with In powder transforms the allylic α-nitroesters to the corresponding α,α-disubstituted α-amino esters.
Topics: Alkynes; Amino Acids; Catalysis; Coordination Complexes; Esters; Hydrogen; Rhodium; Stereoisomerism
PubMed: 33411337
DOI: 10.1002/anie.202014015 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2022The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly... (Review)
Review
The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly functionalized carbo- and heterocyclic products. Although rhodium- and palladium-based catalysts have been commonly used for these reactions, more recent work has demonstrated nickel catalysis is also highly effective, in many cases offering unique reactivity and access to products that might otherwise not be readily available. This review gives an overview of nickel-catalyzed arylative cyclizations of alkyne- and allene-tethered electrophiles using arylboron reagents. The scope of the reactions is discussed in detail, and general mechanistic concepts underpinning the processes are described.
Topics: Alkadienes; Alkynes; Catalysis; Cyclization; Indicators and Reagents; Nickel; Rhodium
PubMed: 34986277
DOI: 10.1002/chem.202104230 -
Journal of the American Chemical Society Mar 2021Selective carbon-carbon (C-C) bond formation in chemical synthesis generally requires prefunctionalized building blocks. However, the requisite prefunctionalization...
Selective carbon-carbon (C-C) bond formation in chemical synthesis generally requires prefunctionalized building blocks. However, the requisite prefunctionalization steps undermine the overall efficiency of synthetic sequences that rely on such reactions, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without prefunctionalized building blocks. In this transformation several classes of unactivated internal acceptor alkynes can be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. This method is facilitated by a tailored P,N-ligand that enables regioselective addition and suppresses secondary /-isomerization of the product. The reaction is scalable and can operate effectively with as low as 0.5 mol % catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.
Topics: Alkynes; Carbon; Catalysis; Oxidation-Reduction; Palladium; Propanols; Stereoisomerism
PubMed: 33683868
DOI: 10.1021/jacs.0c12565 -
Molecules (Basel, Switzerland) Sep 2016The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an... (Review)
Review
The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.
Topics: Alkynes; Azides; Catalysis; Click Chemistry; Copper
PubMed: 27607998
DOI: 10.3390/molecules21091174 -
Journal of Medicinal Chemistry May 2023Combinatorial library screening increasingly explores chemical space beyond the Ro5 (bRo5), which is useful for investigating "undruggable" targets but suffers...
Combinatorial library screening increasingly explores chemical space beyond the Ro5 (bRo5), which is useful for investigating "undruggable" targets but suffers compromised cellular permeability and therefore bioavailability. Moreover, structure-permeation relationships for bRo5 molecules are unclear partially because high-throughput permeation measurement technology for encoded combinatorial libraries is still nascent. Here, we present a permeation assay that is scalable to combinatorial library screening. A liposomal fluorogenic azide probe transduces permeation of alkyne-labeled molecules into small unilamellar vesicles via copper-catalyzed azide-alkyne cycloaddition. Control alkynes (e.g., propargylamine, various alkyne-labeled PEGs) benchmarked the assay. Cell-permeable macrocyclic peptides, exemplary bRo5 molecules, were alkyne labeled and shown to retain permeability. The assay was miniaturized to microfluidic droplets with high assay quality (' ≥ 0.5), demonstrating excellent discrimination of photocleaved known membrane-permeable and -impermeable model library beads. Droplet-scale permeation screening will enable pharmacokinetic mapping of bRo5 libraries to build predictive models.
Topics: Alkynes; Azides; Catalysis; Copper; Gene Library; Liposomes; Peptides; Pharmacokinetics
PubMed: 37075027
DOI: 10.1021/acs.jmedchem.3c00138