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Annual Review of Chemical and... Jun 2022Natural products are a diverse class of biologically produced compounds that participate in fundamental biological processes such as cell signaling, nutrient... (Review)
Review
Natural products are a diverse class of biologically produced compounds that participate in fundamental biological processes such as cell signaling, nutrient acquisition, and interference competition. Unique triple-bond functionalities like isonitriles and alkynes often drive bioactivity and may serve as indicators of novel chemical logic and enzymatic machinery. Yet, the biosynthetic underpinnings of these groups remain only partially understood, constraining the opportunity to rationally engineer biomolecules with these functionalities for applications in pharmaceuticals, bioorthogonal chemistry, and other value-added chemical processes. Here, we focus our review on characterized biosynthetic pathways for isonitrile and alkyne functionalities, their bioorthogonal transformations, and prospects for engineering their biosynthetic machinery for biotechnological applications.
Topics: Alkynes; Biological Products; Biosynthetic Pathways
PubMed: 35236086
DOI: 10.1146/annurev-chembioeng-092120-025140 -
Applied and Environmental Microbiology Apr 2020Ammonia monooxygenase (AMO) is a key nitrogen-transforming enzyme belonging to the same copper-dependent membrane monooxygenase family (CuMMO) as the particulate methane...
Ammonia monooxygenase (AMO) is a key nitrogen-transforming enzyme belonging to the same copper-dependent membrane monooxygenase family (CuMMO) as the particulate methane monooxygenase (pMMO). The AMO from ammonia-oxidizing archaea (AOA) is very divergent from both the AMO of ammonia-oxidizing bacteria (AOB) and the pMMO from methanotrophs, and little is known about the structure or substrate range of the archaeal AMO. This study compares inhibition by C to C linear 1-alkynes of AMO from two phylogenetically distinct strains of AOA, " Nitrosocosmicus franklandus" C13 and " Nitrosotalea sinensis" Nd2, with AMO from and pMMO from (Bath). An increased sensitivity of the archaeal AMO to short-chain-length alkynes (≤C) appeared to be conserved across AOA lineages. Similarities in C to C alkyne inhibition profiles between AMO from AOA and pMMO from suggested that the archaeal AMO has a narrower substrate range than AMO. Inhibition of AMO from " Nitrosocosmicus franklandus" and by the aromatic alkyne phenylacetylene was also investigated. Kinetic data revealed that the mechanisms by which phenylacetylene inhibits " Nitrosocosmicus franklandus" and are different, indicating differences in the AMO active site between AOA and AOB. Phenylacetylene was found to be a specific and irreversible inhibitor of AMO from " Nitrosocosmicus franklandus," and it does not compete with NH for binding at the active site. Archaeal and bacterial ammonia oxidizers (AOA and AOB, respectively) initiate nitrification by oxidizing ammonia to hydroxylamine, a reaction catalyzed by ammonia monooxygenase (AMO). AMO enzyme is difficult to purify in its active form, and its structure and biochemistry remain largely unexplored. The bacterial AMO and the closely related particulate methane monooxygenase (pMMO) have a broad range of hydrocarbon cooxidation substrates. This study provides insights into the AMO of previously unstudied archaeal genera, by comparing the response of the archaeal AMO, a bacterial AMO, and pMMO to inhibition by linear 1-alkynes and the aromatic alkyne, phenylacetylene. Reduced sensitivity to inhibition by larger alkynes suggests that the archaeal AMO has a narrower hydrocarbon substrate range than the bacterial AMO, as previously reported for other genera of AOA. Phenylacetylene inhibited the archaeal and bacterial AMOs at different thresholds and by different mechanisms of inhibition, highlighting structural differences between the two forms of monooxygenase.
Topics: Alkynes; Ammonia; Archaea; Oxidoreductases
PubMed: 32086308
DOI: 10.1128/AEM.02388-19 -
The Journal of Organic Chemistry Jul 2023A novel method for the construction of a cyclopenta[]quinoline ring via cyclization of 3-bromoindoles with internal alkynes in the presence of palladium is described....
A novel method for the construction of a cyclopenta[]quinoline ring via cyclization of 3-bromoindoles with internal alkynes in the presence of palladium is described. The formation of the cyclopenta[]quinoline ring is proposed from a double [1,5] carbon sigmatropic rearrangement of the spirocyclic cyclopentadiene intermediate, which is generated in situ from the cyclization of 3-bromoindoles with internal alkynes involving a sequential double alkyne insertion into the carbon-palladium bond and dearomatization of indole. The present studies have developed a novel ring-expansion reaction of the pyrrole ring to pyridine via one carbon insertion into the C2-C3 bond of indoles and provided a simple and distinct route for the construction of tricyclic fused-quinoline derivatives that are not easy to access with conventional methods.
Topics: Cyclization; Palladium; Alkynes; Molecular Structure; Catalysis; Quinolines
PubMed: 37339369
DOI: 10.1021/acs.joc.3c00716 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2015An iron-catalyzed diboration reaction of alkynes with bis(pinacolato)diboron (B2pin2) and external borating agents (MeOB(OR)2) affords diverse symmetrical or...
An iron-catalyzed diboration reaction of alkynes with bis(pinacolato)diboron (B2pin2) and external borating agents (MeOB(OR)2) affords diverse symmetrical or unsymmetrical cis-1,2-diborylalkenes. The simple protocol for the diboration reaction can be extended to the iron-catalyzed carboboration of alkynes with primary and, unprecedentedly, secondary alkyl halides, affording various tetrasubstituted monoborylalkenes in a highly stereoselective manner. DFT calculations indicate that a boryliron intermediate adds across the triple bond of an alkyne to afford an alkenyliron intermediate, which can react with the external trapping agents, borates and alkyl halides. In situ trapping experiments support the intermediacy of the alkenyl iron species using radical probe stubstrates.
Topics: Alkynes; Catalysis; Iron; Molecular Structure; Stereoisomerism
PubMed: 25631242
DOI: 10.1002/chem.201406595 -
Organic Letters Jun 2023A copper-catalyzed disilylative cyclization of silicon-containing internal alkynes with silylboronates has been developed for the synthesis of...
A copper-catalyzed disilylative cyclization of silicon-containing internal alkynes with silylboronates has been developed for the synthesis of 3-silyl-1-silacyclopent-2-enes. The reaction proceeded regio- and -selectively under simple and mild conditions by employing a combination of nucleophilic silicon donors and electrophilic silicon acceptors. The reaction could also be extended to the synthesis of a 1-germacyclopent-2-ene and a silicon-centered spirocyclic compound by using appropriate alkyne substrates.
Topics: Silicon; Copper; Alkynes; Catalysis; Cyclization
PubMed: 37227424
DOI: 10.1021/acs.orglett.3c01526 -
Journal of the American Chemical Society Aug 2022A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a...
A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late stage. Requisite unnatural amino acid building blocks are easily prepared in an enantiopure form using C-H activation and decarboxylative cross-coupling tactics.
Topics: Alkynes; Amino Acids; Cyclization; Phenylpropionates
PubMed: 35926121
DOI: 10.1021/jacs.2c05892 -
Nature Communications Aug 2022Macrocycles have fascinated scientists for over half a century due to their aesthetically appealing structures and broad utilities in chemical, material, and biological...
Macrocycles have fascinated scientists for over half a century due to their aesthetically appealing structures and broad utilities in chemical, material, and biological research. However, the efficient preparation of macrocycles remains an ongoing research challenge in organic synthesis because of the high entropic penalty involved in the ring-closing process. Herein we report a photocatalyzed thiol-yne click reaction to forge diverse sulfur-containing macrocycles (up to 35-membered ring) and linear C2-linked 1,2-(S-S/S-P/S-N) functionalized molecules, starting from the simplest alkyne, acetylene. Preliminary mechanistic experiments support a visible light-mediated radical-polar crossover dihydrothiolation process. This operationally straightforward reaction is also amenable to the synthesis of organometallic complexes, bis-sulfoxide ligand and a pleuromutilin antibiotic drug Tiamulin, which provides a practical route to synthesize highly valued compounds from the feedstock acetylene gas.
Topics: Acetylene; Alkynes; Click Chemistry; Sulfhydryl Compounds
PubMed: 36008444
DOI: 10.1038/s41467-022-32723-0 -
Organic & Biomolecular Chemistry Sep 2022The hydroarylation of alkynes, alkenes, and allenes is a cost-effective and efficient way to incorporate unsaturated moieties into aromatic substrates. This review... (Review)
Review
The hydroarylation of alkynes, alkenes, and allenes is a cost-effective and efficient way to incorporate unsaturated moieties into aromatic substrates. This review focuses on gold-catalyzed hydroarylation, which produces aromatic alkenes, diaryl-alkanes, heterocycles, carbocycles, and arylbutadienes by directly functionalizing C-H bonds. Without the need for prefunctionalization, direct functionalization of aromatic C-H bonds with unsaturated moieties (alkyne, alkene, allene) provides an efficient synthetic strategy with fewer reaction steps. This review offers an overview of the recently developed hydroarylation processes catalyzed by gold. Mechanisms of hydroarylation alkyne, alkene, allene, and arene activation receive special attention.
Topics: Alkadienes; Alkanes; Alkenes; Alkynes; Catalysis; Gold
PubMed: 36069264
DOI: 10.1039/d2ob00960a -
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 -
Biochimica Et Biophysica Acta Aug 2014Polyene lipids and alkyne lipids allow study of lipid organization, dynamics and metabolism. Both types of lipids contain multiple bonds as the essential functional... (Review)
Review
Polyene lipids and alkyne lipids allow study of lipid organization, dynamics and metabolism. Both types of lipids contain multiple bonds as the essential functional group, leading to minimal disturbance of the hydrophobic properties on which the characteristic behavior of lipids is based. Polyene lipids can directly be traced due to their intrinsic fluorescence, while alkyne lipids need the copper-catalyzed click reaction to an azido-reporter for detection. This review describes recent developments in synthesis and application of both types of lipid analogs with emphasis on metabolic tracing and microscopy imaging. This article is part of a Special Issue entitled Tools to study lipid functions.
Topics: Alkynes; Hydrophobic and Hydrophilic Interactions; Lipids; Polyenes
PubMed: 24412758
DOI: 10.1016/j.bbalip.2013.12.018