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A selective synthesis of unsymmetrically functionalized disiloxanes via the subsequent hydrosilylation of internal alkynes in the first step, and alkynes (terminal or internal) or 1,3-diynes in the second, with 1,1,3,3-tetramethyldisiloxane (1) is presented for the first time. Using developed approaches performed in a stepwise or one-pot manner a new family of disubstituted disiloxanes was obtained which had previously been inaccessible by other synthetic methods. Moreover, symmetrically functionalized disiloxanes were obtained by direct hydrosilylation of 2 equivalents of terminal or internal alkynes with 1, showing the unique versatility of the hydrosilylation process. Three examples of symmetric disiloxanes were characterized by single crystal X-ray diffraction for the first time. As a result, a wide group of new compounds which can find potential applications as building blocks or coupling agents was obtained and characterized., (© 2023. The Author(s).)

1-Iodoalkynes and 1,3-diynes are versatile chemical intermediates and pharmaceutically valuable ingredients. In this study, copper mediated on-DNA alkyne iodination and Cadiot-Chodkiewicz coupling are developed for the first time. This generates diverse, systematic, and unprecedented topographic structural features, which could be invaluable as molecular recognition agents for drug discovery in DEL screening.

A straightforward, efficient, and selective method for the preparation of novel boryl-functionalized enynes or dienes via [Pt(PPh 3 ) 4 ]-catalyzed diboration of a broad spectrum of symmetrical and unsymmetrical 1,3-diynes was developed. The catalytic cycle of diboration was proposed on the basis of low-temperature 31 P NMR studies. An alternative isolation method via product condensation on a cold finger was developed, which, in contrast to previous literature reports, eliminates the need for the additional transformation of rapidly decomposing enynyl pinacol boronates to more stable silica-based column chromatography derivatives during the separation step. To prove the efficiency of this simple catalytic protocol, bisboryl-functionalized enynes were synthesized in a gram scale and tested as useful building blocks in advanced organic transformations, such as hydrosilylation and Suzuki and sila-Sonogashira couplings. The presence of silyl, boryl, as well as other functions like halogen or alkoxy in their structures builds a new class of multifunctionalized enynes that might be modified in various chemical reactions.

An efficient synthetic organic transformation was developed to access isoquinoline-substituted isobenzofurans by reaction of substituted 1,5-diynes with isoquinoline N -oxides. Moderate to excellent yields of isoquinoline-derived isobenzofurans were achieved by formation of a new C-C and two C-O bonds in the presence of copper catalyst in one pot. whereas quinoline-substituted isobenzofurans were obtained when the reaction was conducted using quinoline N -oxides and 1,5-diynes in the presence copper catalyst.

An efficient intramolecular cyclization reaction was developed to achieve indenone derivatives. The substituted 1,5-diyenes were converted to the corresponding indenones via a gold-catalyzed organic transformation, and moderate to excellent yields of the title molecules were obtained via formation of two C=O and one C-C bonds under mild reaction conditions in one pot., (© 2022 Wiley-VCH GmbH.)

We report here a three-component, Cu(I)-catalyzed hexadehydro-Diels-Alder (HDDA) benzyne 1,2-difunctionalization reaction. This protocol allowed the introduction of two different carbon-based substituents onto the in situ-generated benzyne. These substituents were terminal monoynes or diynes partnered with propargylic, benzylic, or allylic chlorides. An example of a sequential HDDA reaction is demonstrated using the product of a 1,3-diyne and a propargylic halide, itself a newly created HDDA precursor.

We investigated the mechanism of action of panaxynol (PAL) extract from the root of Saposhnikovia diviaricata (Turcz.) Schischk for treating acute liver injury caused by lipopolysaccharide (LPS) and D-galactosamine (D-Gal N) in mice. A mouse model of acute liver failure induced by LPS/D-Gal N was established. Mice were divided randomly into three equal groups: control group, LPS/D-Gal N group and PAL group. After seven days of continuous PAL administration, all animals except controls were injected with 50 μg/kg LPS and 800 mg/kg D-Gal N; blood and liver samples were collected after 8 h. Compared to the LPS/D-Gal N group, the levels of catalase, glutathione and superoxide dismutase were increased in the liver of the PAL group. The inflammatory response index indicated that PAL attenuated LPS/D Gal N-induced liver pathological injury and decreased levels of hepatic malondialdehyde, serum alanine aminotransferase, aspartate transaminase, tumor necrosis factor-α, and interleukins 1β and 6. PAL also inhibited LPS/D-Gal N induced nuclear factor-kappa B (Nf-κB), inhibitor kappa B-α (IκB-α) activation, and up-regulated Nrf2 and heme oxygenase-1 (HO-1) expression. PAL can prevent LPS/D-Gal N induced acute liver injury by activating Nrf2/HO-1 to stimulate antioxidant defense and inhibit the IkB-α/NF-κB signaling pathway.

In response to biotic stress, plants produce suites of highly modified fatty acids that bear unusual chemical functionalities. Despite their chemical complexity and proposed roles in pathogen defense, little is known about the biosynthesis of decorated fatty acids in plants. Falcarindiol is a prototypical acetylenic lipid present in carrot, tomato, and celery that inhibits growth of fungi and human cancer cell lines. Using a combination of untargeted metabolomics and RNA sequencing, we discovered a biosynthetic gene cluster in tomato (Solanum lycopersicum) required for falcarindiol production. By reconstituting initial biosynthetic steps in a heterologous host and generating transgenic pathway mutants in tomato, we demonstrate a direct role of the cluster in falcarindiol biosynthesis and resistance to fungal and bacterial pathogens in tomato leaves. This work reveals a mechanism by which plants sculpt their lipid pool in response to pathogens and provides critical insight into the complex biochemistry of alkynyl lipid production., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In total and formal syntheses of dictyodendrins A, B, C, D, E and F, the key step involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki-Miyaura coupling), C2 (acylation), N3 (alkylation) and C5 positions (Ullmann coupling) provided divergent access to dictyodendrins. Some dictyodendrin analogues exhibited inhibitory activities toward CDK2/CycA2 and GSK3.

Both solvent-free and acetonitrile-containing cationic molybdenum imido alkylidene N-heterocyclic carbene (NHC) complexes of the general formula [Mo(NR')(CHCMe 2 R)(NHC)(X) + A - ] (R' = 2,6-Cl 2 -C 6 H 3 , tBu, 2-CF 3 -C 6 H 4 , 2-tBu-C 6 H 4 , 2,6-iPr 2 -C 6 H 3 , 2,6-Me 2 -C 6 H 3 ; R = Me, Ph; NHC = 1,3-dimesitylimidazol-2-ylidene (IMes), 1,3-di-iPr-imidazol-2-ylidene (IPr), 1,3,5-triphenyl-1,3,4-triazol-2-ylidene); X = CF 3 SO 3 , C 6 F 5 O, OCH(CF 3 ) 2 , OC(CF 3 ) 3 , pyrrolide, C 6 F 5 COO, 2,6-(CF 3 ) 2 -C 6 H 3 COO; A - = B(Ar F ) 4 - , Al(OC(CF 3 ) 3 ) 4 - ), have been investigated for their propensity to cyclopolymerize 4,4-disubstituted 1,6-heptadiynes. All metal complexes contain a stereogenic (chiral) metal center, which accounts for the high reactivity and high regioselectivity of insertion (>99%) that are observed for all metal complexes, leading to highly conjugated, α-insertion-derived polyenes that are based on a highly regular polymer backbone and that show absorption maxima close to 600 nm. With the chiral monomer 4-(ethoxycarbonyl)-4-(1S,2R,5S)-(-)-menthoxycarbonyl-1,6-heptadiyne, high syndiospecifity (>99% syndiotactic) is observed. A mechanism explaining the high regio- and stereoselectivity is presented. Thus, α-addition of the monomers proceeds chain-end-controlled trans to the NHC and is preferred over β-addition through intramolecular Mo-O chelation. Insertion of the monomers entails double inversion at the stereogenic metal center in the course of one complete monomer insertion., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Metabolic incorporation of bioorthogonal functional groups into chromatin, followed by copper-free conjugation reactions, often gives low yields due to steric hindrance. Here we report that a cationic Sondheimer diyne derivative "DiMOC" rapidly reacts with azide groups in duplex DNA that are otherwise unreactive toward aliphatic cyclooctynes such as bicyclo[6.1.0]nonyne (BCN). DiMOC reversibly intercalates into duplex DNA and undergoes tandem strain-promoted cross-linking of two different azide groups to give DNA-DiMOC-"X" cross-links, where "X" theoretically represents a fluorescent probe, affinity tag, RNA, protein, carbohydrate, and so forth. As a proof of principle, the metabolic incorporation of azide-modified nucleosides into cellular DNA or RNA, followed by treatment with DiMOC and a fluorescent azide enabled visualization of newly synthesized nucleic acids in whole cells.

Polyacetylenic compounds isolated from Panax species are comprised of non-polar C17 compounds, exhibiting anti-inflammatory, antitumor, and antifungal activities. Panaxynol represents the major component of the essential oils of ginseng. We investigated whether panaxynol isolated from Panax vietnamensis (Vietnamese ginseng, VG) could prevent cisplatin-induced renal damage induced in vitro and in vivo. Cisplatin-induced apoptotic cell death was observed by staining with annexin V conjugated with Alexa Fluor 488, and western blotting evaluated the molecular mechanism. Panaxynol at concentrations above 0.25 μM prevented cisplatin-induced LLC-PK1 porcine renal proximal tubular cell death. LLC-PK1 cells treated with cisplatin demonstrated an increase in apoptotic cell death, whereas pretreatment with 2 and 4 μM panaxynol decreased this effect. Cisplatin demonstrated a marked increase in the phosphorylation of c-Jun N-terminal kinase (JNK), P38, and cleaved caspase-3. However, pretreatment with 2 and 4 μM panaxynol reversed the upregulated phosphorylation of JNK, P38, and the expression of cleaved caspase-3. We confirmed that the protective effect of panaxynol isolated from P. vietnamensis in LLC-PK1 cells was at least partially mediated by reducing the cisplatin-induced apoptotic damage. In the animal study, panaxynol treatment ameliorated body weight loss and blood renal function markers and downregulated the mRNA expression of inflammatory mediators.

A highly convergent strategy for the synthesis of the natural product (-)-rubriflordilactone B, and the proposed structure of (-)-pseudo-rubriflordilactone B, is described. Late stage coupling of diynes containing the respective natural product FG rings with a common AB ring aldehyde precedes rhodium-catalyzed [2+2+2] alkyne cyclotrimerization to form the natural product skeleton, with the syntheses completed in just one further operation. This work resolves the uncertainty surrounding the identity of pseudo-rubriflordilactone B and provides a robust platform for further synthetic and biological investigations., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Short alphahelical peptide sequences were stabilized through Glaser-Hay couplings of propargylated l- and/or d-serine residues at positions i and i+7. NMR analysis confirmed a full stabilization of the helical structure when a d-Ser (i), l-Ser (i+7) combination was applied. In case two l-Ser residues were involved in the cyclization, the helical conformation is disrupted outside the peptide's macrocycle., (© 2019 European Peptide Society and John Wiley & Sons, Ltd.)

Phytochemical investigation of Polyscias guilfoylei leaves extract (PGE) led to the isolation of nine compounds, that is, ent-labda-8(17),13-diene-15,18-diol (1), stigmasterol (2), spinasterol (3), N-(1,3-dihydroxyoctadecan-2-yl) palmitamide (4), panaxydiol (5), 3-O-β-d-glucopyranosylstigmasta-5,22-diene-3-β-ol (6), (8Z)-2-(2 hydroxypentacosanoylamino) octadeca-8-ene-1,3,4-triol (7), 4-hydroxybenzoic acid (8), and tamarixetin 3,7-di-O-α-L-rhamnopyranoside (9). Compound 4 is reported in this study for the first time in nature whereas compound 9 is reported for the second time. Structural elucidation of the compounds was carried out using Nuclear Magnetic Resonance and Electrospray Ionization coupled with Mass Spectrometry spectroscopic analyses. PGE and compounds 4 and 9 exhibited weak cytotoxicity against both MCF-7 and HCT-116 cell lines using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide assay. The antimicrobial activity of PGE and compounds 4 and 9 was evaluated using the agar diffusion method. Escherichia coli was the most susceptible Gram-negative bacteria toward PGE with a minimum inhibitory concentration value of 9.76 μg/mL, whereas compounds 4 and 9 did not show any antimicrobial activity. Compound 4 exhibited promising inhibition of histamine release using U937 human monocytes with an IC50 value of 38.65 μg/mL.

We present the application of a Glaser-Hay diyne coupling for the synthesis of conformationally constrained N α -amino acid amides with different diyne ring sizes. Twelve-membered rings were the smallest rings that could be prepared by this approach. We observed the formation of triethylammonium adducts in the cases of smaller (10- and 11-membered) rings. Calculation of the conformational barriers for the cyclization reactions of various ring sizes demonstrated that the formation of amino acid-derived smaller rings by this reaction is thermodynamically unfavorable.

A chiral amino alcohol based ligand was found to promote the highly enantioselective addition of terminal conjugated diynes to aromatic and aliphatic aldehydes. The combination of easily available C 2 -symmetric (R)- and (S)-BINOL with Ti(OiPr) 4 , Zn powder, and EtI was also found to catalyze the asymmetric addition of 1,3-diynes to aldehydes under mild reaction conditions, and thus, both enantiomers of the chiral conjugated diynols could be prepared with high enantioselectivities. The resulting optically active conjugated diynols were found to have potential anticancer activities with significant differences against HepG2 and HeLa cancer cells, and remarkable enantioselective cytotoxicity was observed for the first time., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nuclear factor- (erythroid-derived 2) like 2 (Nrf2) is a transcription factor that regulates the expression of a battery of antioxidant, anti-inflammatory, and cytoprotective enzymes including heme oxygenase-1 (Hmox1, Ho-1) and NADPH:quinone oxidoreductase-1 (Nqo1). The isothiocyanate sulforaphane (SF) is widely understood to be the most effective natural activator of the Nrf2 pathway. Falcarinol (FA) is a lesser studied natural compound abundant in medicinal plants as well as dietary plants from the Apiaceae family such as carrot. We evaluated the protective effects of FA and SF (5 mg/kg twice per day in CB57BL/6 mice) pretreatment for one week against acute intestinal and systemic inflammation. The phytochemical pretreatment effectively reduced the magnitude of intestinal proinflammatory gene expression (IL-6, Tnf α /Tnf α r, Inf γ , STAT3, and IL-10/IL-10r) with FA showing more potency than SF. FA was also more effective in upregulating Ho-1 at mRNA and protein levels in both the mouse liver and the intestine. FA but not SF attenuated plasma chemokine eotaxin and white blood cell growth factor GM-CSF, which are involved in the recruitment and stabilization of first-responder immune cells. Phytochemicals generally did not attenuate plasma proinflammatory cytokines. Plasma and intestinal lipid peroxidation was also not significantly changed 4 h after LPS injection; however, FA did reduce basal lipid peroxidation in the mesentery. Both phytochemical pretreatments protected against LPS-induced reduction in intestinal barrier integrity, but FA additionally reduced inflammatory cell infiltration even below negative control.

Three diynes, octadec-17-ene-9,11-diynoate ethyl (1: ), 8-hydroxy-octadeca-13,17-diene-9,11-diynoate ethyl (2: ), and 8-hydroxy-octadec-13-ene-9,11-diynoate ethyl (3: ), were isolated from Ongokea gore seed oil. The structure assignment of these three compounds was based according to chemical and spectroscopic data. They were screened against Plasmodium falciparum , the parasite that causes malaria. In vitro micro-test (Mark III, supported by the World Health Organization) was developed to assess the response of P. falciparum to the isolated three compounds, and statistical analysis were performed for determination of the concentration that inhibits 50% of the parasite maturation (IC 50 ). Two of the three diynes (2: and 3: ) showed a very effective in vitro antimalarial activity with an IC 50 of 4.5 and 1.7 µM, respectively. Compound 3: exhibited better activity than quinine (IC 50 1.9 µM), the drug reference, while compound 1: had no antimalarial activity (IC 50  > 125 µM). In the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity screening, all compounds showed no toxicity (mean IC 50 of 90 µM for each compound)., Competing Interests: The authors declare no conflicts of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Classical synthetic approaches to highly unsaturated polyene/yne natural products rely on iterative cross-coupling of linear fragments. Herein, we present an expeditious and unified approach to the unsaturated backbone of polyacetylenes via domino cuprate addition/4π-electrocyclic ring opening of a stereodefined cyclobutene intermediate. This sets the stage for a detailed biological assessment of the role of Virol A and Cicutoxin as inhibitors of GABA induced chloride currents, providing further insight into the interaction of these highly potent toxins towards the GABA A receptor, including the structure-activity relationship of the derivatives.

This study reports the first Co 2 (CO) 8 -catalyzed [2+2+2] polycyclotrimerization by the transformation of internal ethynyl groups of aromatic diyne monomers. The reaction yields polycyclotrimers of polyphenylene-type with either hyperbranched or partly crosslinked architecture. The homopolycyclotrimerization of the monomers with two ethynyl groups per one molecule, namely 1,4-bis(phenylethynyl)benzene, 4,4'-bis(phenylethynyl)biphenyl, and 4-(phenylethynyl)phenylacetylene, gives partly crosslinked, insoluble polyphenylenes. The soluble, hyperbranched polyphenylenes are generated via copolycyclotrimerization of 1,4-bis(phenylethynyl)benzene with 1,2-diphenylacetylene (average number of ethynyl groups per monomer molecule < 2). This one-step polycyclotrimerization path to hyperbranched or partly crosslinked polyphenylenes is an alternative to the synthesis of these polymers by Diels-Alder transformation of substituted cyclopentadienones. All polyphenylenes prepared exhibit photoluminescence with emission maxima ranging from 381 to 495 nm. Polyphenylenes with a less compact packing of segments are microporous (specific surface area up to 159 m 2 g -1 ), which is particularly important in the case of soluble polyphenylenes because they can be potentially used to prepare microporous layers., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: The 3,4-diyne substituted isocoumarins have been designed, synthesized and explored as potential anti-proliferative agents., Method: Ultrasound assisted synthesis of these compounds was carried out by using a three-step method involving (i) Pd/C-Cu catalyzed cross-coupling between the methyl 2-iodobenzoate and buta- 1,3-diynylbenzene followed by (ii) I2-mediated electrophilic cyclization of the resultant 2-(alk-1- ynyl)benzoate ester and (iii) subsequent alkynylation of 4-iodo-3-(phenylethynyl)-isocoumarin under Pd/C-Cu catalysis., Conclusion: The synthesized compounds showed promising growth inhibition when tested against MDA-MB 231 and K562 cancer cell lines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In total and formal syntheses of dictyodendrins B, C, E, and F, the key step involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki-Miyaura coupling), C2 (addition to an aldehyde), N3 (alkylation), and C5 positions (Ullman coupling) provided divergent access to dictyodendrins., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

Despite significant advances in the last three decades towards high yielding syntheses of rotaxanes, the preparation of systems constructed from more than two components remains a challenge. Herein we build upon our previous report of an active template copper-catalyzed azide-alkyne cycloaddition (CuAAC) rotaxane synthesis with a diyne in which, following the formation of the first mechanical bond, the steric bulk of the macrocycle tempers the reactivity of the second alkyne unit. We have now extended this approach to the use of 1,3,5-triethynylbenzene in order to successively prepare [2]-, [3]- and [4]rotaxanes without the need for protecting group chemistry. Whilst the first two iterations proceeded in good yield, the steric shielding that affords this selectivity also significantly reduces the efficacy of the active template (AT)-CuAAC reaction of the third alkyne towards the preparation of [4]rotaxanes, resulting in severely diminished yields.

During a screening program for new agrochemicals from Chinese medicinal herbs, the ethanol extract of Notopterygium incisum rhizomes was found to possess strong nematicidal activity against the two species of nematodes, Bursaphelenchus xylophilus and Meloidogyne incognita. Based on bioactivity-guided fractionation, the four constituents were isolated from the ethanol extract and identified as columbianetin, falcarindiol, falcarinol, and isoimperatorin. Among the four isolated constituents, two acetylenic compounds, falcarindiol and falcarinol (2.20-12.60 μg/mL and 1.06-4.96 μg/mL, respectively) exhibited stronger nematicidal activity than two furanocoumarins, columbianetin, and isoimperatorin (21.83-103.44 μg/mL and 17.21-30.91 μg/mL, respectively) against the two species of nematodes, B. xylophilus and M. incognita. The four isolated constituents also displayed phototoxic activity against the nematodes. The results indicate that the ethanol extract of N. incisum and its four isolated constituents have potential for development into natural nematicides for control of plant-parasitic nematodes.

Background: The treatment of microbial infections is becoming increasingly challenging because of limited therapeutic options and the growing number of pathogenic strains that are resistant to current antibiotics. There is an urgent need to identify molecules with novel modes of action to facilitate the development of new and more effective therapeutic agents. The anti-mycobacterial activity of the C17 diyne natural products falcarinol and panaxydol has been described previously; however, their mode of action remains largely undetermined in microbes. Gene expression profiling was therefore used to determine the transcriptomic response of Mycobacterium smegmatis upon treatment with falcarinol and panaxydol to better characterize the mode of action of these C17 diynes., Results: Our analyses identified 704 and 907 transcripts that were differentially expressed in M. smegmatis after treatment with falcarinol and panaxydol respectively. Principal component analysis suggested that the C17 diynes exhibit a mode of action that is distinct to commonly used antimycobacterial drugs. Functional enrichment analysis and pathway enrichment analysis revealed that cell processes such as ectoine biosynthesis and cyclopropane-fatty-acyl-phospholipid synthesis were responsive to falcarinol and panaxydol treatment at the transcriptome level in M. smegmatis. The modes of action of the two C17 diynes were also predicted through Prediction of Activity Spectra of Substances (PASS). Based upon convergence of these three independent analyses, we hypothesize that the C17 diynes inhibit fatty acid biosynthesis, specifically phospholipid synthesis, in mycobacteria., Conclusion: Based on transcriptomic responses, it is suggested that the C17 diynes act differently than other anti-mycobacterial compounds in M. smegmatis, and do so by inhibiting phospholipid biosynthesis.

In the classic Diels-Alder [4 + 2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4π (diene) and 2π (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels-Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced by, for example, four in the tetradehydro-Diels-Alder (TDDA) and by six in the hexadehydro-Diels-Alder (HDDA) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4π + 2π cycloaddition reaction that generates a different, highly reactive intermediate known as an α,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, α,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels-Alder (PDDA) reaction-a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC≡N), although non-participants in aza-HDDA reactions, readily function as the 2π component in PDDA cyclizations to produce, via trapping of the α,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.

We report herein the fabrication of novel microarrays based on air-stable functional lipid monolayers over silicon using a combination of e-beam lithography and lift-off. We demonstrate these microarrays can be use as ultrasensitive platform for Kelvin probe force microscopy in sensing experiments. Specificity of the detection is given by the functional group grafted at the lipid headgroup. The arrays developed for the detection of ferric ions, Fe(3+), using a γ-pyrone derivative chelator, demonstrate subpicomolar limit of detection with high specificity. In addition, the technique takes advantage of the structure of the array with the silicon areas playing the role of reference for the measurement, and we determine critical pattern dimensions below which the probe size/shape impacts the measured results.

Diarylbutadiyne derivatives are ideal monomers for providing the π-electron-conjugated system of polydiacetylenes (PDAs). The geometrical parameters for diacetylene topochemical polymerization are known. However, control of the molecules under these parameters is yet to be addressed. This work shows that by simply tailoring diarylbutadiyne with amide side-chain substituents, the arrangement of the substituents and the resulting hydrogen bond framework allows formation of π-electron-conjugated PDA., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd-catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence.

Meliacarpin-type limonoids are an important class of organic insecticides. Their syntheses are challenging due to their chemical complexity. Here, we report the highly enantio- and diastereoselective synthesis of the left fragments of azadirachtin I and 1-cinnamoylmelianolone, being two important family members of meliacarpin-type limonoids, via pairwise palladium- and gold-catalyzed cascade reactions. Gold-catalyzed reactions of 1,7-diynes were performed as model studies, and the efficient construction of tetracyclic late-stage intermediates was achieved on the basis of this key transformation. Our unique route gave both of the left fragments in 23 steps from the commercially available chiral starting material (-)-carvone. This study significantly advances research on the synthesis of the meliacarpin-type limonoids.

An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

The first fully conjugated bis-cyclopropenone (photo-DIBOD), a derivative of dibenzo[a,e][8]annulene, has been synthesized. 350-420 nm irradiation of this robust compound results in the efficient formation of dibenzo [a,e] cyclooctadiyne, an unstable, but useful SPAAC cross-linking reagent. Since photo-DIBO doesn't react with organic azides, this method allows for the spatiotemporal control of the ligation of two azide-tagged substrates.

The convergent total synthesis of the marine natural product phosphoiodyn A, a nanomolar agonist of human peroxisome proliferator-activated receptor delta (hPPARδ), was achieved in five steps total from commercially available and inexpensive starting materials. The synthesis relies on the unprecedented regioselective hydrozirconation of a terminal acetylene in the presence of a conjugated 1,3-diyne and on ammonolysis of a β-chlorophosphonic acid monoester. The scheme also provides the newly isolated placotylene A, an inhibitor of bone marrow-derived macrophage (BMM) differentiation.

Although chemotherapy plays a vital role in treating non-Hodgkin lymphomas, the clinical applications are limited because of intolerable side-effects and multidrug resistance at the beginning or during the course of therapy. In this study, we successfully fabricated a CD20-targeting immuno-liposome based on 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC-8,9PC), which can form intermolecular cross-linking through the diacetylenic group by ultraviolet irradiation. This immuno-liposome showed appropriate size distribution, well-defined regular spherical structure, favorable biocompatibility, high serum stability, and prolonged circulation time in blood vessels. The in and ex vivo experiments demonstrate enhanced tumor suppression abilities against both wild-type and resistant non-Hodgkin lymphomas for liposomal doxorubicin when compared with free drugs. The outstanding antitumor activities are attributed to the accumulation and retention of liposomal drugs in malignant tissues and cells, which are realized by the co-operation of active targeting via antibody-antigen reaction and passive targeting via enhanced permeability and retention effect., (© 2015 John Wiley & Sons A/S.)

The Glaser-Hay diyne coupling proved to be an efficient cyclisation approach towards diyne containing peptidic macrocycles. A variety of tetrapeptide-based macrocyclic 1,3-diynes were obtained from O-propargylated serine or tyrosine residues using Cu(OAc)2·H2O and NiCl2 under an O2-atmosphere. The effect of the linear 1,3-diyne on peptide conformations was studied by NMR and compared with a macrocycle bearing a saturated linker.

Transition-metal catalysis has revolutionized the field of organic synthesis by facilitating the construction of complex organic molecules in a highly efficient manner. Although these catalysts are typically based on precious metals, researchers have made great strides in discovering new base metal catalysts over the past decade. This Account describes our efforts in this area and details the development of versatile Ni complexes that catalyze a variety of cycloaddition reactions to afford interesting carbocycles and heterocycles. First, we describe our early work in investigating the efficacy of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and isocyanate. The use of sterically hindered, electron donating NHC ligands in these reactions significantly improved the substrate scope as well as reaction conditions in the syntheses of a variety of pyrones and pyridones. The high reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps. We describe the development and mechanistic analysis of Ni/NHC catalysts that couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric reactions confirmed a hetero-oxidative coupling pathway associated with this Ni-catalyzed cycloaddition. We then describe a series of new substrates for Ni-catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones, tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C σ-bond activation and an 8π-insertion of vinylcyclopropane and tropone, respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones also requires Ni-catalyzed C-C σ-bond activation to form N- and O-containing heterocycles.

α-Oxo gold carbenes generated in situ via the gold-catalyzed selective oxidation of 4-oxahepta-1,6-diynes were effectively trapped by internal alkynes, resulting in the formation of 2H-pyran-3(6H)-ones, , and chromen-3(4H)-ones, , upon facile trapping the vinyl cation intermediates by an external N-oxide and internal aryl ring system.

A method for the synthesis of phosphabenzenes under iron catalysis is described. Thus, the FeI2 -catalyzed [2+2+2] cycloaddition of diynes with phosphaalkynes in m-xylene gave a variety of phosphabenzenes in good to high yields (up to 87 % yield)., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly efficient one-pot approach for the synthesis of carbonyl 2-amino-pyrimidines from 1,3-diynes and guanidine in the presence of Cs2CO3 and DMSO has been described. In these reactions, 1,3-diynes act as a precursor of buta-1,2,3-trienes and guanidine serves as the N-C[double bond, length as m-dash]N source for the construction of pyrimidines. This methodology proves to be a tandem regioselective heterocyclization of 1,3-diynes with guanidine and selective oxidation with DMSO.

Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.

A gold-catalyzed cascade cyclization of aniline derivatives bearing a conjugated diyne moiety was developed. Following the 5-endo-dig indole formation, subsequent 7-endo-dig cyclization predominated over 6-exo-dig cyclization to give the indole fused with a seven-membered ring in good yields.

The translation of organometallic reactions into a microwave reactor has numerous advantages. Herein, we describe the application of a previously developed solid-supported Glaser-Hay reaction to microwave conditions. Overall, an array of diynes has been prepared demonstrating the ability to conduct chemoselective reactions in the microwave within 20 min compared to the 16 h thermal conditions. Moreover, non-microwave transparent alkynes have been found to react more quickly, preventing catalyst quenching, and resulting in higher yields.

The effects of various pulsed electric field (PEF) parameters on the extraction of polyacetylenes from carrot slices were investigated. Optimised conditions with regard to electric field strength (1-4 kV/cm), number of pulses (100-1500), pulse frequency (10-200 Hz) and pulse width (10-30 μs) were identified using response surface methodology (RSM) to maximise the extraction of falcarinol (FaOH), falcarindiol (FaDOH) and falcarindiol-3-acetate (FaDOAc) from carrot slices. Data obtained from RSM and experiments fitted significantly (p < 0.0001) the proposed second-order response functions with high regression coefficients (R2) ranging from 0.82 to 0.75. Maximal FaOH (188%), FaDOH (164.9%) and FaDOAc (166.8%) levels relative to untreated samples were obtained from carrot slices after applying PEF treatments at 4 kV/cm with 100 number of pulses of 10 μs at 10 Hz. The predicted values from the developed quadratic polynomial equation were in close agreement with the actual experimental values with low average mean deviations (E%) ranging from 0.68% to 3.58%.

We report a cholesterol imaging method using rationally synthesized phenyl-diyne cholesterol (PhDY-Chol) and stimulated Raman scattering (SRS) microscope. The phenyl-diyne group is biologically inert and provides a Raman scattering cross section that is 88 times larger than the endogenous C = O stretching mode. SRS microscopy offers an imaging speed that is faster than spontaneous Raman microscopy by three orders of magnitude, and a detection sensitivity of 31 μM PhDY-Chol (~1,800 molecules in the excitation volume). Inside living CHO cells, PhDY-Chol mimics the behavior of cholesterol, including membrane incorporation and esterification. In a cellular model of Niemann-Pick type C disease, PhDY-Chol reflects the lysosomal accumulation of cholesterol, and shows relocation to lipid droplets after HPβCD treatment. In live C. elegans, PhDY-Chol mimics cholesterol uptake by intestinal cells and reflects cholesterol storage. Together, our work demonstrates an enabling platform for study of cholesterol storage and trafficking in living cells and vital organisms.

Indole synthesis by a gold(I)-catalyzed intermolecular formal [4+2] reaction between 1,3-diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3-diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7-disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Transition-metal free heterocyclization reaction of 1,3-diynes with N,O-bis(trimethylsiyl)acetamide was accomplished in the presence of t-BuOK and acetonitrile at 120 °C. This method regioselectively gave 2,4,5-trisubstituted oxazoles in yields up to 97%.

Nonafluorobutanesulfonyl azide is a highly efficient reagent for the copper-catalyzed coupling of terminal alkynes to give symmetrical and unsymmetrical 1,3-diynes in good to excellent yields and with good functional group compatibility. The reaction is extremely fast (<10 min), even at low temperature (−78 °C), and requires substoichiometric amounts of a simple copper(I) or copper(II) salt (2–5 mol %) and an organic base (0.6 mol %). A possible mechanistic pathway is briefly discussed on the basis of model DFT theoretical calculations. The quantitative assessment of the safety of use and shelf stability of nonafluorobutanesulfonyl azide has confirmed that this reagent is a superior and safe alternative to other electrophilic azide reagents in use today.

A gold-catalyzed cycloisomerization of 1,6-diynes containing an ynamide propargyl ester or carbonate moiety has been developed that provides an attractive route to a diverse-substituted 3-acyloxy-1,4-dihydrocyclopenta[b]indoles. Mechanistic studies indicate that the reaction likely proceeds through a competitive 1,2-OAc migration followed by [3+2] cycloaddition of the vinyl gold-carbenoid intermediate with the pendant triple bond. The synthetic utility of the obtained cyclopenta[b]indole products was demonstrated by their efficient transformations by deprotection or double-bond isomerization reactions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)