20795-53-3Relevant academic research and scientific papers
Novel σ1 antagonists designed for tumor therapy: Structure – activity relationships of aminoethyl substituted cyclohexanes
Kopp, Nicole,Holtschulte, Catharina,B?rgel, Frederik,Lehmkuhl, Kirstin,Friedland, Kristina,Civenni, Gianluca,Laurini, Erik,Catapano, Carlo V.,Pricl, Sabrina,Humpf, Hans-Ulrich,Schepmann, Dirk,Wünsch, Bernhard
, (2021)
Depending on the substitution pattern and stereochemistry, 1,3-dioxanes 1 with an aminoethyl moiety in 4-position represent potent σ1 receptor antagonists. In order to increase the stability, a cyclohexane ring first replaced the acetalic 1, 3-dioxane ring of 1. A large set of aminoethyl substituted cyclohexane derivatives was prepared in a six-step synthesis. All enantiomers and diastereomers were separated by chiral HPLC at the stage of the primary alcohol 7, and their absolute configuration was determined by CD spectroscopy. Neither the relative nor the absolute configuration had a large impact on the σ1 affinity. The highest σ1 affinity was found for cis-configured benzylamines (1R,3S)-11 (Ki = 0.61 nM) and (1S,3R)-11 (Ki = 1.3 nM). Molecular dynamics simulations showed that binding of (1R,3S)-11 at the σ1 receptor is stabilized by the typical polar interaction of the protonated amino moiety with the carboxy group of E172 which is optimally oriented by an H-bond interaction with Y103. The lipophilic interaction of I124 with the N-substituent also contributes to the high σ1 affinity of the benzylamines. The antagonistic activity was determined in a Ca2+ influx assay in retinal ganglion cells. The enantiomeric cis-configured benzylamines (1R,3S)-11 and (1S,3R)-11 were able to inhibit the growth of DU145 cells, a highly aggressive human prostate tumor cell line. Moreover, cis-11 could also inhibit the growth of further human tumor cells expressing σ1 receptors. The experimentally determined logD7.4 value of 3.13 for (1R,3S)-11 is in a promising range regarding membrane penetration. After incubation with mouse liver microsomes and NADPH for 90 min, 43% of the parent (1R,3S)-11 remained unchanged, indicating intermediate metabolic stability. Altogether, nine metabolites including one glutathione adduct were detected by means of LC-MS analysis.
Synthesis, structure, and function of pcp pincer transition-metal-complex- bound norvaline derivatives
Takaya, Hikaru,Iwaya, Takashi,Ogata, Kazuki,Isozaki, Katsuhiro,Yokoi, Tomoya,Yoshida, Ryota,Yasuda, Nobuhiro,Seike, Hirofumi,Takenaka, Toshio,Nakamura, Masaharu
, p. 1910 - 1914 (2013)
A PCP pincer palladium-complex-bound norvaline, Boc-l-[Pd]Nva-OMe, was synthesized and fully characterized by NMR, FT-ICR-MS, and X-ray crystallography. Selective N- and C-terminus transformations of Boc-l-[Pd]Nva-OMe were performed by conventional deprotection-condensation procedures to afford lipophilic palladium-bound norvaline derivatives without metal detachment. The N-/C-bisfunctionalized palladium-bound norvaline showed self-assembly properties, as evidenced by supramolecular gel formation. The catalytic activity of the supramolecular gel was assessed in the 1,4-conjugate addition of phenylboronic acid.
Phosphine-olefin ligands: A facile dehydrogenative route to catalytically active rhodium complexes
Douglas, Thomas M.,Notre, Jerome Le,Brayshaw, Simon K.,Frost, Christopher G.,Weller, Andrew S.
, p. 3408 - 3410 (2006)
Facile, metal-mediated, (acceptorless) dehydrogenation of tricyclopentyl phosphine directly affords rhodium chelating phosphine-olefin complexes, some of which are catalytically active for 1,4-additions. The Royal Society of Chemistry 2006.
Radical cyclizations of 2-(ω-haloalkylthio)enones to thiapolycycloalkanones
Ponaras, Anthony A.,Zaim, ?mer
, p. 2279 - 2282 (2000)
Radical cyclization of 2-(ω-haloalkylthio)enones gives predominantly fused-thiapolycycloalkanones. (C) 2000 Elsevier Science Ltd.
Synthesis of β-Selenylated Cyclopentanones via Photoredox-Catalyzed Selenylation/Ring-Expansion Cascades of Alkenyl Cyclobutanols
Jung, Hye Im,Kim, Dae Young
, p. 1361 - 1365 (2019)
A photoredox strategy to access β-selenated cyclic ketone derivatives through the coupling reaction of 1-(1-arylvinyl)cyclobutanols with diselenides under blue LED irradiation and an air atmosphere was developed. This reaction employs the easily accessibl
Asymmetric Induction with Amidocuprates
Bertz, Steven H.,Dabbagh, Gary,Sundararajan, G.
, p. 4953 - 4959 (1986)
Optically active amines such as (R)- or (S)-α-methylbenzylamine and (4S,5S)-(+)-5-amino-2,2-dimethyl-4-phenyl-1,3-dioxane can be lithiated with an alkyllithium an added to an organocopper(I) compound, prepared from a lithium reagent and CuI, to give a chi
MORE HIGHLY MIXED, HIGHER ORDER CYANOCUPRATES "rt(2-thienyl)Cu(CN)Li2". EFFICIENT REAGENTS WHICH PROMOTE SELECTIVE LIGAND TRANSFER
Lipshutz, Bruce H.,Kozlowski, Joseph A.,Parker, David A.,Nguyen, Sam L.,McCarthy, Keith E.
, p. 437 - 448 (1985)
The combination of an organolithium (RTLi) and 2-lithiothiophene (2-thienyl) with CuCN forms a new reagents, "RT(2-thienyl)Cu(CN)Li2".This species selectively transfers the RT ligand in substitution reactions with epoxides and halides.In conjugate addition processes, the cuprate reacts with unhindered substrates, while β,β-disubstituted cases unexpectedly afford products resulting from 1,2-addition of the thiophene group.The prospects for use of these reagents in the synthesis of polyene macrolide antibiotics are discussed.
Synthesis of dibromobenzobarrelene derivatives and catalytic activity of their rhodium complexes
Schlesinger, Maik,Hofmann, Max,Rueffer, Tobias,Schaarschmidt, Dieter,Lang, Heinrich,Theilacker, Sergio,Schuermann, Markus,Jurkschat, Klaus,Mehring, Michael
, p. 2930 - 2939 (2013)
A novel synthetic route based on [4+2] cycloaddition for dibromobenzobarrelene derivatives starting from in situ generated 3,5-dibromo-1,2-didehydrobenzene and mesitylene, 1,2,4,5-tetramethylbenzene, 1,2,3,5-tetramethylbenzene, pentamethylbenzene, 1,3-dimethoxybenzene, and 2,4,6-trimethylbromobenzene, respectively, was developed. Thus, six novel dibromobenzobarrelenes with diverse substitution patterns at the barrelene framework including chiral derivatives are reported. The benzobarrelene 6,8-dibromo-1,3,10-trimethyl-1,4-dihydro-1,4-ethenonaphthalene (1a) was functionalized at the annulated benzene ring to give three novel carboxylic acids and two novel phosphonic acid esters. Selected benzobarrelene complexes with RhICl were tested for their catalytic activity in the 1,4-addition of phenylboronic acid towards cyclohex-2-enone. Turnover frequencies up to 3405 h-1 were observed, which are among the highest reported so far for Rh-diene complexes in this type of C-C coupling reaction. The synthesis by means of a [4+2] cycloaddition approach of six novel dibromobenzobarrelenes with diverse substitution patterns at the barrelene framework, including chiral derivatives, is reported as well as the functionalization of 6,8-dibromo-1,3,10-trimethyl-1,4-dihydro-1,4- ethenonaphthalene to give carboxylic acid and phosphonic acid ester derivatives. Copyright
Detailed Structural Analysis of a Self-Assembled Vesicular Amphiphilic NCN-Pincer Palladium Complex by Using Wide-Angle X-Ray Scattering and Molecular Dynamics Calculations
Hamasaka, Go,Muto, Tsubasa,Andoh, Yoshimichi,Fujimoto, Kazushi,Kato, Kenichi,Takata, Masaki,Okazaki, Susumu,Uozumi, Yasuhiro
, p. 1291 - 1298 (2017)
Wide-angle X-ray scattering experiments and all-atomistic molecular dynamics calculations were performed to elucidate the detailed structure of bilayer vesicles constructed by self-assembly of an amphiphilic palladium NCN-pincer complex. We found an excel
Low-Temperature Intramolecular [4+2] Cycloaddition of Allenes with Arenes for the Synthesis of Diene Ligands
Hari, Durga Prasad,Pisella, Guillaume,Wodrich, Matthew D.,Tsymbal, Artem V.,Tirani, Farzaneh Fadaei,Scopelliti, Rosario,Waser, Jerome
supporting information, p. 5475 - 5481 (2021/01/21)
The intramolecular [4+2] cycloaddition between arenes and allenes first reported by Himbert gives rapid access to rigid polycyclic scaffolds. Herein, we report a one-pot oxyalkynylation/cycloaddition reaction proceeding under mild conditions (23–90 °C) an
