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Pd-catalyzed aminocarbonylation in the presence of Xantphos as a ligand was used to transform lactam-, lactone-, and thiolactone-derived triflates into N-methoxy-N-methyl or morpholine Weinreb amides. The method could also be applied to synthesize dienones in which one of the double bonds is embedded in a heterocyclic moiety, as useful substrates for Nazarov cyclization.

Three different procedures are compared to obtain properly substituted divinyl ketones in which one of the double bonds is embedded in a five-membered heterocyclic structure and therefore suitable to produce cyclopenta-fused pyrrole, derivatives by the acid-catalyzed Nazarov reaction. A convergent procedure base on the umpolung to a vinylstannane gave acceptable yields of the divinyl ketone, which forms a key intermediate in the synthesis of roseophilin.

Reporting on the torquoselectivity in the cyclization of 2-substituted five-membered azacycle and 2- and 4-substituted six-membered oxacycle derivatives. The reaction is highly diastereoselective with 2-substituted five-membered lactam derivatives 11a and 11b and leads to cis disubstituted cyclopenta-fused pyrrolines 13a and 13b, respectively.

The reaction between 1-metalated 1-ethoxy 1,3-dienes and electrophiles yields (E)-1-substituted 1-ethoxy 1,3-dienes. These alpha-substituted alkoxy dienes produce alpha, beta-unsaturated carbonyl compounds on acidic hydrolysis via a reaction pathway involving carbanionic intermediates. Use of crotonaldehyde as an electrophile produces an addition product, which on hydrolysis, yields three products depending on experimental conditions.

An approach for the synthesis of functionalized trienes and regioselective formation of medium-ring lactones is discussed. Both reactions involves intramolecular Diels-Alder reaction which generate the macrocyclic rings. The reaction is performed at varying temperature and solvents to determine both the regioselectivity and stereoselectivity of the synthetic pathway. H nuclear magnetic spectra of the reaction is discussed.

3-ethoxyhexa-3,5-dien-1-ol is prepared from a reaction between an electrophile, ethylene oxide and an alpha-metalated alkoxy diene which involves an epoxide ring opening. Synthesis of 2- and 2,6-disubstituted tetrahydro-4H-pyran-4-ones involves these alpha-substituted alkoxy dienes as intermediates. Propylene oxide yields a mixture of cis and trans compounds. 1H NMR and gas chromatography analyses are employed to calculate the cis-trans ratio.

Answers to some queries such as, whether the presence of the N atom in the cyclic moiety of conjugated triene is necessary to attain electrocyclization under certain assumption are presented. Demonstration of the synthetic usefulness of the methodology, for the diasteroselective synthesis of cyclopenta-fused heterocyclic compounds, is presented.

Research has been conducted on palladium-catalyzed cross- coupling reactions of alpha-alkoxyboronates with lactam-derived vinyl triflates. The methodology developed for the preparation of azacyclic compounds is described.

The gold(I)-catalyzed cyclization of N-Boc-protected 6-alkynyl-3,4-dihydro-2H-pyridines, prepared by the Sonogashira coupling of lactam-derived enol triflates or phosphates, provides vinylogous amides, which are useful intermediates in the synthesis of natural compounds. The Au(I)-catalyzed reaction is carried out with Ph3PAuOTf as a catalyst and proceeds via a 6-endo-dig cyclization to form a vinylgold species that after protodeauration generates a cyclic carbamate intermediate. This intermediate is in most cases not isolated, but the addition of a base to the reaction mixture rapidly and quantitatively delivers the target vinylogous amide. The first synthesis of a natural compound from Sonneratia hainanensis has been accomplished by this approach. [ABSTRACT FROM AUTHOR]

Provides details on the reaction of `alpha'-metalated alkoxy dienes with various electrophiles and on the acidic hydrolysis of `alpha'-substituted alkoxy dienes. Details of previous studies; Description of experiments; Results of experiments; Discussion of experiments.

Studies the use of alkoxydienyl and alkoxystyrylboronates for Pd-catalyzed cross-coupling reactions. Functionalization of lactam-derived vinyl triflates; Classification of azacyclic compounds; Synthesis of nitrogen-containing heterocycles.

A methodology for the total and modulable synthesis of (4 Z )-lachnophyllum lactone ( 1 ), on a gram scale, is reported for the first time. The present work started with the design of a retrosynthetic pathway for the target compound, with the key step identified in Pd-Cu bimetallic cascade cross-coupling cyclization. (4 Z )-Lachnophyllum lactone ( 1 ) is an acetylenic furanone previously isolated, in a low amount, from the organic extract of the autotrophic weed Conyza bonariensis . Tested against the stem parasitic weed Cuscuta campestris in a seedling growth bioassay, (4 Z )-lachnophyllum lactone ( 1 ) showed almost 85% of inhibitory activity up to 0.3 mM in comparison with the control. At the same concentration, the compound displayed radicle growth inhibitory activity of the root parasitic weeds Orobanche minor and Phelipanche ramosa higher than 70 and 40%, respectively. Surprisingly, the compound showed a high percentage of inhibition, up to 0.1 mM, on C. bonariensis seed germination too. This versatile synthetic strategy was also used to obtain two further natural analogues, namely, (4 E )-lachnophyllum lactone ( 8 ) and (4 Z ,8 Z )-matricaria lactone ( 9 ), that showed, in most cases, the same inhibitory trend with slight differences, highlighting the importance of the stereochemistry and unsaturation of the side chain. Furthermore, all of the compounds showed antifungal activity at 1 mM reducing the mycelial growth of the olive pathogen Verticillium dahliae . The design and implementation of scalable and modulable total synthesis on a gram scale of acetylenic furanones allow the production of a large amount of these natural products, overcoming the limit imposed by isolation from natural sources. The results of the present study pave the way for the development of ecofriendly bioinspired pesticides with potential application in agrochemical practices as alternative to synthetic pesticides.

Phytohormones have significant roles in redox metabolism, inflammatory responses, and cellular survival mechanisms within the microenvironment of the mammalian brain. Herein, we identified the mammalian molecular targets of three representative strigolactone (SL) analogues structurally derived from apocarotenoids and the functional equivalent of plant hormones. All tested SL analogues have an inhibitory effect on NLRP3 inflammasome-mediated IL-1β release in murine microglial cells. However, IND and EGO10 became prominent among them due to their high potency at low micromolar doses. All SL analogues dose-dependently suppressed the release and expression of proinflammatory factors. For EGO10 and IND, IC 50 values for iNOS-associated NO secretion were as low as 1.72 and 1.02 μM, respectively. In silico analyses revealed that ( S )-EGO10 interacted with iNOS, NLRP3, and Keap1 ligands with the highest binding affinities among all stereoisomeric SL analogues. Although all compounds were effective in microglial Mox phenotype polarization, 4-Br-debranone exhibited a differential pattern for upregulating Nrf2-driven downstream enzymes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Strigolactones (SLs), carotenoid-derived phytohormones, control the plant response and signaling pathways for stressful conditions. In addition, they impact numerous cellular processes in mammalians and present new scaffolds for various biomedical applications. Recent studies demonstrated that SLs possess potent antitumor activity against several cancer cells. Herein, we sought to elucidate the inhibitory effects of SL analogs on the growth and survival of human brain tumor cell lines. Among four tested SLs, we showed for the first time that two lead bioactiphores, indanone-derived SL and EGO10, can inhibit cancer cell proliferation, induce apoptosis, and induce G1 cell cycle arrest at low concentrations. SL analogs were marked by increased expression of Bax/Caspase-3 genes and downregulation of Bcl-2. In silico studies were conducted to identify drug-likeness, blood-brain barrier penetrating properties, and molecular docking with Bcl-2 protein. Taken together, this study indicates that SLs may be promising antiglioma agents, presenting novel pharmacophores for further preclinical and clinical assessment.

The reactivity of "furan-ynes" in combination with pyridine and quinoline N -oxides in the presence of a Au(I) catalyst, has been studied, enabling the synthesis of three different heterocyclic scaffolds. Selective access to two out of the three possible products, a dihydropyridinone and a furan enone, has been achieved through the fine-tuning of the reaction conditions. The reactions proceed smoothly at room temperature and open-air, and were further extended to a broad substrate scope, thus affording functionalized dihydropyridinones and pyranones.

A stereoselective approach to the synthesis of (E)-alkoxydienylamines (2) is described, starting from alpha,beta-unsaturated acetals (1) and aryl imines, under superbasic conditions. These can be readily converted into alpha-arylglycine derivatives (3) by mild acidic hydrolysis or, in turn, cyclized under oxidative conditions in the presence of a Pd catalyst to 2,3,4,5-tetrasubstituted pyrroles (4).

[reaction: see text] The Suzuki-Miyaura cross-coupling reaction between alpha-ethoxydienyl boronates and lactone-derived vinyl triflates affords functionalized 6-(1-ethoxy-1,3-butadienyl)dihydropyran derivatives that undergo a Nazarov electrocyclic reaction under mild acidic conditions to give functionalized spirocyclic ketones. The product distribution and the stereoselectivity of the process are strongly dependent on the substitution of both the alpha-ethoxydiene and dihydropyran moieties. High stereoselectivity is observed in the presence of a C2-substituent on the dihydropyran moiety. The results are explained in terms of transition state geometries.

[reaction: see text] alpha,beta-Unsaturated acetals afford, in the presence of the LIC-KOR superbase, 1-alkoxybuta-1,3-dienes. These substrates cross couple with aryl derivatives in the presence of Pd catalyst (Heck conditions) in a regio- and stereoselective mode. With dialkyl acetals, the reaction affords arylated dienes; on the other hand, in the case of 1,3-dioxane derivatives, the final outcome of the process formally corresponds to the direct gamma-arylation reaction of the starting alpha,beta-unsaturated material.

Alkoxy-functionalized butadienyl- and styrylboronic esters have been synthesized starting from alpha,beta-unsaturated acetals. These derivatives readily cross-couple with aryl substrates, and the obtained products can be transformed under mild conditions into aromatic ketones, achieving the same result as an acylation reaction. [reaction: see text]