- Cobalt-Catalyzed Enantioselective C–H Arylation of Indoles
-
Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is the most obvious disconnection to construct such compounds, the direct enantioselective C–H arylation through the concomitant induction of the chiral information remains extremely challenging and uncommon. Herein, the unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation is reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies and DFT computation revealed an uncommon mechanism for this asymmetric transformation, with the oxidative addition being the rate- and enantio-determining step. Excellent stereoselectivities were reached (up to 96% ee), while using an unusual N-heterocyclic carbene ligand bearing an essential remote substituent. Attractive dispersion interactions along with positive C–H-π interactions exerted by the ligand were identified as key factors to guarantee the excellent enantioselection.
- Ackermann, Lutz,Jacob, Nicolas,Oliveira, Jo?o C. A.,Wencel-Delord, Joanna,Zaid, Yassir
-
supporting information
p. 798 - 806
(2022/02/03)
-
- Access to Polycyclic Sulfonyl Indolines via Fe(II)-Catalyzed or UV-Driven Formal [2 + 2 + 1] Cyclization Reactions of N-((1H-indol-3-yl)methyl)propiolamides with NaHSO3
-
A variety of structurally novel polycyclic sulfonyl indolines have been synthesized via FeCl2-catalyzed or UV-driven intramolecular formal [2 + 2 + 1] dearomatizing cyclization reactions of N-(1H-indol-3-yl)methyl)propiolamides with NaHSO3 in an aqueous medium. The reactions involve the formation of one C-C bond and two C-S bonds in a single step.
- Lu, Lin,Luo, Chenguang,Peng, Hui,Jiang, Huanfeng,Lei, Ming,Yin, Biaolin
-
supporting information
p. 2602 - 2605
(2019/04/30)
-
- Electrochemically Enabled C3-Formylation and -Acylation of Indoles with Aldehydes
-
Reported herein is an effective strategy for oxidative cross-coupling of indoles with various aldehydes. The strategy is based on a two-step transformation via a well-known Mannich-type reaction and a C-N bond cleavage for carbonyl introduction. The key step - the C-N bond cleavage of the Mannich product - was enabled by electrochemistry. This strategy (with over 40 examples) ensures excellent functional-group tolerance as well as late-stage functionalization of pharmaceutical molecules.
- Yang, Liquan,Liu, Zhaoran,Li, Yujun,Lei, Ning,Shen, Yanling,Zheng, Ke
-
supporting information
p. 7702 - 7707
(2019/10/19)
-
- Indole-substituted hydrazide derivatives and uses thereof
-
The invention discloses indole-substituted hydrazide derivatives and a use thereof, concretely relates to novel indole-substituted hydrazide derivatives and a medicinal composition including the abovecompounds, a use of the derivatives and the medicinal composition in the protection of nerve cells, and also relates to a method for preparing the compounds and the medicinal composition, and a use of the compounds and the medicinal composition in the preparation of drugs for treating diseases associated with glutamate excitotoxicity and oxidative stress damage or free radicals, or neurodegenerative diseases, especially the Alzheimer disease.
- -
-
Paragraph 0309; 0361-0364
(2018/11/03)
-
- Visible Light-Driven C-3 Functionalization of Indoles over Conjugated Microporous Polymers
-
Metal-free and heterogeneous organic photocatalysts provide an environmentally friendly alternative to traditional metal-based catalysts. This paper reports a series of carbazole-based conjugated microporous polymers (CMPs) with tunable redox potentials and explores their photocatalytic performance with regard to C-3 formylation and thiocyanation of indoles. Conjugated polymers were synthesized through FeCl3 mediated Friedel-Crafts reactions, and their redox potentials were well regulated by simply altering the nature of the core (i.e., 1,4-dibenzyl, 1,3,5-tribenzyl, or 1,3,5-triazin-2,4,6-triyl). The resulting CMPs exhibited high surface areas, visible light absorptions, and tunable semiconductor-range band gaps. With the highest oxidative capability, CMP-CSU6 derived from 1,3,5-tri(9H-carbazol-9-yl)benzene showed the highest efficiency for C-3 formylation and thiocyanation of indoles at room temperature. Notably, the as-made catalysts can be easily recovered with good retention of photocatalytic activity and reused at least five times, suggesting good recyclability. These results are significant for constructing high-performance porous polymer catalysts with tunable photoredox potentials targeting an efficient material design for catalysis.
- Zhang, Weijie,Tang, Juntao,Yu, Wenguang,Huang, Qiao,Fu, Yu,Kuang, Guichao,Pan, Chunyue,Yu, Guipeng
-
p. 8084 - 8091
(2018/07/30)
-
- CuCl2/TBHP-mediated direct chlorooxidation of indoles
-
CuCl2/TBHP-mediated direct chlorooxidation of indole derivatives under simple aerobic conditions was reported, leading to facile preparations of a range of 3,3-disubstituted 3-chlorooxindoles in good yields and selectivities.
- Wang, Huifei,Liu, Dong,Chen, Huiyu,Li, Jing,Wang, David Zhigang
-
supporting information
p. 7073 - 7076
(2015/08/19)
-
- I2-mediated C3-formylation of indoles by tertiary amine and H2O
-
An I2-promoted 3-formylation of free (N-H) and N-substituted indoles with tetramethylethylenediamine (TMEDA) and H2O as the carbonyl source is achieved, providing 3-formylindole in moderate to excellent yields with good functional gr
- Zhang, Bo,Liu, Bin,Chen, Jianbin,Wang, Jiehui,Liu, Miaochang
-
supporting information
p. 5618 - 5621
(2014/12/11)
-
- Aerobic transition-metal-free visible-light photoredox indole C-3 formylation reaction
-
An aerobic visible-light-promoted indole C-3 formylation reaction catalyzed by Rose Bengal has been developed. This transition-metal-free process employs molecular oxygen as the terminal oxidant and uses TMEDA as the one-carbon source through C-N bond cleavage. The reaction is compatible with a variety of functional groups.
- Li, Xiang,Gu, Xiangyong,Li, Yongjuan,Li, Pixu
-
p. 1897 - 1900
(2014/06/24)
-
- The ammonium-promoted formylation of indoles by DMSO and H2O
-
DMSO and H2O is an efficient combination in the NH 4OAc-promoted formylation of indole, where DMSO serves as a C1 carbon source. The mechanism study reveals that the procedure involves a usual and unusual Pummerer reaction.
- Fei, Haiyang,Yu, Jintao,Jiang, Yan,Guo, Huan,Cheng, Jiang
-
supporting information
p. 7092 - 7095
(2013/10/22)
-
- The copper-catalyzed C-3-formylation of indole C-H bonds using tertiary amines and molecular oxygen
-
A copper-catalyzed formylation reaction has been developed by employing oxygen (O2) as the clean oxidant. The C-H bonds of indoles were C-3-formylated by tetramethylethylenediamine (TMEDA) and water (H2O; in situ formed and external added water) as the carbonyl source in moderate to good yields with good functional group tolerance. Thus, it represents a facile procedure leading to 3-formylindoles. Copyright
- Chen, Jianbin,Liu, Bin,Liu, Dongfang,Liu, Shan,Cheng, Jiang
-
supporting information
p. 2438 - 2442
(2012/11/07)
-
- Identification of trans-4-[1-[[7-fluoro-2-(1-methyl-3-indolyl)-6- benzoxazolyl]acetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid as a potent, orally active VLA-4 antagonist
-
For the purpose of obtaining orally potent VLA-4 inhibitors, we have carried out structural modification of the (N′-phenylureido)phenyl group in compound 1, where the group was found to be attributed to poor pharmacokinetic profile in our previous research. Through modification, we have identified several compounds with both potent in vitro activity and improved oral exposure. In particular, compound 7e with 7-fluoro-2-(1-methyl-1H-indol-3- yl)-1,3-benzoxazolyl group as a novel replacement of the (N′-phenylureido) phenyl group significantly inhibited eosinophil infiltration into bronchoalveolar lavage fluid at 15 mg/kg in an Ascaris-antigen-induced murine bronchial inflammatory model, and its efficacy was comparable to that of the anti-mouse α4 antibody (R1-2).
- Setoguchi, Masaki,Iimura, Shin,Sugimoto, Yuuichi,Yoneda, Yoshiyuki,Chiba, Jun,Watanabe, Toshiyuki,Muro, Fumihito,Iigo, Yutaka,Takayama, Gensuke,Yokoyama, Mika,Taira, Tomoe,Aonuma, Misato,Takashi, Tohru,Nakayama, Atsushi,MacHinaga, Nobuo
-
experimental part
p. 1201 - 1212
(2012/03/26)
-
- Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators
-
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan. Herein, we report a structure-activity study on a series of 3-(2-(pyridyl)ethenyl)indoles. More than 70 novel derivatives were synthesized, and their TDO inhibitory potency was evaluated. The rationalization of the structure-activity relationships (SARs) revealed essential features to attain high TDO inhibition and notably a dense H-bond network mainly involving His55 and Thr254 residues. Our study led to the identification of a very promising compound (58) displaying good TDO inhibition (Ki = 5.5 μM), high selectivity, and good oral bioavailability. Indeed, 58 was chosen for preclinical evaluation.
- Dolu?i?, Eduard,Larrieu, Pierre,Moineaux, Laurence,Stroobant, Vincent,Pilotte, Luc,Colau, Didier,Pochet, Lionel,Van Den Eynde, Beno?t,Masereel, Bernard,Wouters, Johan,Frédérick, Rapha?l
-
supporting information; scheme or table
p. 5320 - 5334
(2011/10/02)
-
- VLA-4 INHIBITORS
-
The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.
- -
-
-
- Probing the phytopathogenic stem rot fungus with phytoalexins and analogues: unprecedented glucosylation of camalexin and 6-methoxycamalexin
-
The remarkable metabolism of the cruciferous hytoalexins camalexin and 6-methoxycamalexin by the stem rot phytopathogen Sclerotinia sclerotiorum is reported. The biotransformations yielded camalexins glucosylated at N-1 or C-6 of the indole ring, with substantially lower antifungal activity than camalexins. A camalexin analogue with the positions N-1 and C-6 blocked was metabolized but at a much slower rate than the natural hytoalexins. The chemistry involved in the metabolism of natural camalexins and two new analogues, as well as their novel metabolites and respective antifungal activities is described. Copyright
- Pedras, M. Soledade C.,Ahiahonu, Pearson W.K
-
p. 3307 - 3312
(2007/10/03)
-