A straightforward, mild, and transition-metal-free three-component coupling reaction involving arynes, phosphites, and silyl fluorides was developed through Si-F bond activation. Although the Si-F bond is one of the strongest bonds, Si-C bond formation via Si-F bond cleavage with the assistance of bidentate silicon and phosphonium Lewis acids has been successfully achieved. This unprecedented strategy provides a facile approach for synthesizing ortho-silyl-substituted aryl phosphonates.
View Article and Find Full Text PDFA temperature-dependent cascade of reactions between tryptamines and propargylic alcohols was developed to achieve selective formation of pyrroloindoline and pyrrolo[1,2-]indole heterocycles by Ca(II) catalysis. The cascade consists of electrophilic addition of allene at the C3 carbon of indole followed by intramolecular cyclization at 60 °C to yield pyrroloindolines. Furthermore, simultaneous 1,2-allene migration and pyrrolidine ring opening were followed by intramolecular cyclization via C-N bond formation at reflux temperature to obtain pyrrolo[1,2-]indole scaffolds.
View Article and Find Full Text PDFA mild, efficient, and transition-metal-free three-component coupling reaction involving arynes, phosphites, and aldehydes was established to afford 3-mono-substituted benzoxaphosphole 1-oxides. A range of 3-mono-substituted benzoxaphosphole 1-oxides was obtained from both aryl- and aliphatic-substituted aldehydes in moderate to good yields. Moreover, the synthetic utility of the reaction was demonstrated by a Gram-scale reaction and the transformation of the products into various -containing bicycles.
View Article and Find Full Text PDFA mild and efficient three-component thio(seleno)cyano-difluoroalkylation of simple alkenes is demonstrated using an iridium(ruthenium) photocatalyst. This protocol provides a direct and regioselective installation of both C-S(Se)CN [thio(seleno)cyanation] and C-C (difluoroalkylation) bonds.
View Article and Find Full Text PDFWe report the stereocontrolled synthesis of 1,6-diazecanes a tandem aza-Prins type reaction of -acyliminium ions with allylsilanes. It involves an aza-Prins type dimerization and cyclization in a single-step operation. This reaction represents the first example of 10-membered N-heterocycle synthesis using an aza-Prins reaction.
View Article and Find Full Text PDFA regioselective alkylation of β,γ-alkynyl-α-imino esters by visible-light photocatalysis has been developed. This method enables 1,2-addition of methyl, primary, secondary, and tertiary alkyl radicals to the conjugated imines under mild conditions to produce a variety of quaternary alkynyl α-amino acid and cyclic amino acid motifs. Alkyl radicals are generated from alkyl bis(catecholato)silicates with an organic photocatalyst.
View Article and Find Full Text PDFStereoselective synthesis of C-substituted benzo[]quinolizidines via redox-controlled catalytic C-C-bond-forming reactions was carried out. Aerobic DDQ-catalyzed allylation of -Cbz tetrahydroisoquinolines efficiently provided α-allylated products , which were transformed to enones via cross-metathesis reactions using the second-generation Hoveyda-Grubbs catalyst. Palladium-catalyzed hydrogenation of prompted alkene reduction, protecting group removal, and intramolecular reductive amination in one step to afford the desired benzo[]quinolizidines as single diastereomers.
View Article and Find Full Text PDFTwo new pyrrolosesquiterpenes, glaciapyrroles D () and E () were discovered along with the previously reported glaciapyrrole A () from sp. GGS53 strain isolated from deep-sea sediment. This study elucidated the planar structures of and using nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV), and infrared (IR) spectroscopic data.
View Article and Find Full Text PDFAn efficient and transition-metal-free three-component reaction with benzynes formed in situ from 2-(trimethylsilyl)aryl triflate, phosphites, and ketones was developed for the synthesis of benzoxaphosphole 1-oxides. An array of benzoxaphosphole 1-oxides were prepared from both activated and non-activated ketones in moderate to good yields with a broad functional group tolerance. This reaction is useful for preparing organophosphorus compounds encountered in natural products and materials.
View Article and Find Full Text PDFThe tropolone-bearing sesquiterpenes juniperone A () and norjuniperone A () were isolated from the folk medicinal plant , and their structures were determined by a combination of spectroscopic and crystallographic methods. Photojuniperones A1 () and A2 (), bearing bicyclo[3,2,0]heptadienones derived from tropolone, were photochemically produced and structurally identified by spectroscopic methods. Predicted by the machine learning-based assay, significantly inhibited the action of tyrosinase.
View Article and Find Full Text PDFBRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types.
View Article and Find Full Text PDFB-Raf mutation was identified as a key target in cancer treatment. Based on structural features of dabrafenib (potent FDA approved B-Raf inhibitor), the design of new NH-based imidazothiazole derivatives was carried out affording new highly potent derivatives of imidazothiazole-based scaffold with amino substitution on the terminal phenyl ring as well as side chain with sulfonamide group and terminal substituted phenyl ring. In vitro enzyme assay was investigated against V600E B-Raf kinase.
View Article and Find Full Text PDFThe versatile synthesis of (-)-6-desmethyl-fluvirucinine A₁ was accomplished at a 24% overall yield through a thirteen-step process from a known vinylpiperidine. The key part involved the elaboration of the distal stereocenters and a macrolactam skeleton via conformationally-induced diastereocontrol and the iterative aza-Claisen rearrangements of lactam precursors.
View Article and Find Full Text PDFThough many studies have been published about therapeutic potentials of selective 5-HTR ligands, there have been few biased ligands of 5-HTR. The development of potent and selective biased ligands of 5-HTR would be of great help in understanding the relationship between pharmacological effects and G protein/β-arrestin signaling pathways of 5-HTR. In order to identify 5-HTR ligands with biased agonism, we designed and synthesized a series of tetrahydroazepine derivatives 1 and 2 with arylpyrazolo moiety or arylisoxazolo moiety.
View Article and Find Full Text PDFThe copper(I)-catalyzed azide-alkyne cycloaddition reaction has been extensively studied and widely applied in organic synthesis. However, the formation of 1,2,3-triazoles with electron-deficient azide has been a challenging problem. In this report, we have demonstrated the formation of regioselective 1,4-disubstituted 1,2,3-triazoles from various types of aryl terminal alkynes and azidoformates, which are electron-deficient azides, using a commercialized [Cu(CHCN)]PF copper(I) catalyst under mild conditions.
View Article and Find Full Text PDFA concise synthesis of 8-azabicyclo[3.2.1]octanes via sequential oxidative Mannich reactions is described.
View Article and Find Full Text PDFAn efficient synthetic method for establishing chiral α-thio-α-quaternary stereogenic center was successfully developed. The enantioselective α-alkylation of α-acylthiomalonates under phase-transfer catalytic conditions [50% aq. KOH, toluene, -20 °C, and (S,S)-3,4,5-trifluorophenyl-NAS bromide] provided the corresponding α-acylthio-α-alkylmalonates in high chemical yields (up to 99%) and high optical yields (up to 98% ee).
View Article and Find Full Text PDFA divergent synthetic methodology for a tabernaemontanine-related alkaloid was developed. The synthetic route features practical improvements in the Pictet-Spengler cyclization for the tetrahydro-β-carboline intermediate and an unprecedented tandem Reformatsky-aza-Claisen rearrangement to create the core carbon skeleton and stereochemistries of tabernaemontanine-related alkaloids.
View Article and Find Full Text PDFIn our previous research, a novel series of phenylsulfonyl hydrazide derivatives were found to reduce LPS-induced PGE levels in RAW 264.7 macrophage cells via an inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture of phenylsulfonyl hydrazide was formed depending on the reaction conditions, which favor either of two regioisomers.
View Article and Find Full Text PDFWe described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50=274 and 159nM) showing excellent in vitro stability profile.
View Article and Find Full Text PDFActa Crystallogr E Crystallogr Commun
July 2015
In the title compound, C17H17NO4, the cylohexane-1,3-dione ring adopts an envelope conformation with the dimethyl-subsituted C atom as the flap. Its mean plane is inclined to the benzene ring by 7.99 (19)°.
View Article and Find Full Text PDFA synthetic approach toward the tricyclic 5,7,6-membered ring structure of daphnane-family natural products is described. An intramolecular [4 + 3] cycloaddition reaction of furan with an oxypentadienyl cation constructed the oxa-bridged bicyclic structure in a stereoselective fashion. Structural analysis revealed that the desired exo isomer was predominantly acquired through epimerization.
View Article and Find Full Text PDFAn efficient enantioselective synthetic method for α-amido-α-alkylmalonates via phase-transfer catalytic α-alkylation was successfully developed. The α-alkylation of α-amidomalonates under phase-transfer catalytic conditions (50% KOH, toluene, -40 °C) in the presence of (S,S)-3,4,5-trifluorophenyl-NAS bromide afforded the corresponding α-amido-α-alkylmalonates in high chemical yields (up to 99%) and optical yields (up to 97% ee), which could be readily converted to versatile chiral intermediates bearing α-amino quaternary stereogenic centers. The synthetic potential of this methodology was demonstrated via the synthesis of chiral azlactone, oxazoline, and unnatural α-amino acid.
View Article and Find Full Text PDFActa Crystallogr Sect E Struct Rep Online
November 2014
In the title compound, C20H17NO, the dihedral angle between the mean planes of the 4-meth-oxy-phenyl ring and the naphthalene ring is 69.50 (7)°. The meth-oxy group is almost coplanar with the benzene ring to which it is connected [Cb-Cb-Om-Cm torsion angle of -7.
View Article and Find Full Text PDFThis article describes the rapid and diversified synthesis of pyrrolidinyl triazoles for the discovery of mitochondrial permeability transition pore (mPTP) blockers. The 1,3-dipolar cycloaddition of ethynyl trifluoroborate with azidopyrrolidine produced a key intermediate, triazolyl trifluoroborate 4, which subsequently underwent a Suzuki-Miyaura coupling reaction to afford a series of 1,4-disubstituted triazoles 2. Subsequent biological evaluation of these derivatives indicated 2ag and 2aj as the most potent mPTP blockers exhibiting excellent cytochrome P450 (CYP) stability when compared to the previously reported oxime analogue 1.
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