- Palladium-Catalyzed Silacyclization of (Hetero)Arenes with a Tetrasilane Reagent through Twofold C?H Activation
-
The use of an operationally convenient and stable silicon reagent (octamethyl-1,4-dioxacyclohexasilane, ODCS) for the selective silacyclization of (hetero)arenes via twofold C?H activation is reported. This method is compatible with N-containing heteroarenes such as indoles and carbazoles of varying complexity. The ODCS reagent can also be utilized for silacyclization of other types of substrates, including tertiary phosphines and aryl halides. A series of mechanistic experiments and density functional theory (DFT) calculations were used to investigate the preferred pathway for this twofold C?H activation process.
- Wang, Dingyi,Li, Mingjie,Chen, Xiangyang,Wang, Minyan,Liang, Yong,Zhao, Yue,Houk, Kendall N.,Shi, Zhuangzhi
-
-
Read Online
- Rhodium-Catalyzed sp2 C-H Acetoxylation of N-Aryl Azaindoles/N-Heteroaryl Indolines
-
A silver- and copper-free rhodium-catalyzed C-H acetoxylation reaction of azaindoles has been achieved at near ambient temperature employing PIDA as a nonmetallic acetoxy source. The method is highly selective, efficient, and scalable and requires acetic anhydride as the sole additive. The scope of the reaction has been successfully tested with a wide array of medicinally important heterocyclic scaffolds with diverse functional group tolerance. A series of kinetic experiments was conducted to gain detailed insight into the reaction mechanism. The methodology developed could be successfully expanded for C7-acetoxylation of indoline derivatives using pyrimidine as a detachable directing group for the synthesis of 7-hydroxyindole.
- Mishra, Aniket,Vats, Tripta Kumari,Nair, Mahesh P.,Das, Arindam,Deb, Indubhusan
-
-
Read Online
- Cu(I)-Catalyzed Site Selective Acyloxylation of Indoline Using O2 as the Sole Oxidant
-
A Cu(I)-catalyzed regioselective cross-dehydrogenative coupling of indoline with a variety aryl and alkyl carboxylic acids is described. The divergent process for the oxygenation was achieved in satisfactory yields under additive free conditions, which provides an efficient strategy for the regioselective C7 functionalization of indolines using inexpensive copper catalyst. Oxygen as the sole oxidant is required in this protocol. The method is tolerated by a wide range of functional groups. Preliminary mechanistic study provided support for a reversible C?H bond metallation step. (Figure presented.).
- Ahmad, Ashfaq,Dutta, Himangsu Sekhar,Khan, Bhuttu,Kant, Ruchir,Koley, Dipankar
-
-
Read Online
- DUAL-INHIBITORS OF CELLULAR NECROPTOSIS AND FERROPTOSIS FOR USE IN THE TREATMENT OF ORGAN TRANSPLANT PATIENTS
-
The invention relates to chemical compounds for use as a medicament in the prevention of organ transplant rejection and/or transplant organ damage. In embodiments of the invention, the compound inhibits and/or reduces ferroptosis and necroptosis of cells of the transplanted organ. In further embodiments, the patient is at risk of transplant rejection and/or is at risk of or shows signs of ischemia-reperfusion injury and/or necroinflammation.
- -
-
Paragraph 0173
(2021/09/09)
-
- Acyl-Directed ortho-Borylation of Anilines and C7 Borylation of Indoles using just BBr3
-
Indoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N-acyl directing groups enable the C7-selective C?H borylation of indoles using just BBr3. This transformation shows some functional-group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl-directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4-amino-indoles are amenable to this process, with acyl group installation and directed electrophilic C?H borylation enabling selective formation of C5-BPin-indoles.
- Iqbal, Saqib A.,Cid, Jessica,Procter, Richard J.,Uzelac, Marina,Yuan, Kang,Ingleson, Michael J.
-
p. 15381 - 15385
(2019/10/22)
-
- Synthetic approach to telomerase inhibitor dictyodendrin B: Synthesis of the pyrrolo[2,3-c]carbazole core
-
The core structure of the telomerase inhibitor, dictyodendrin B, was synthesized by using the palladium-catalyzed cross-coupling reaction of 3-aryl-1-(2-arylethyl)-4-hydroxy-2,5-bismethoxycarbonylpyrrole triflate with 7-alkoxyindole-3-boronate as the key step.
- Hirao, Shotaro,Sugiyama, Yumiko,Iwao, Masatomo,Ishibashi, Fumito
-
experimental part
p. 1764 - 1772
(2010/03/24)
-
- Novel approaches towards the LTD4/E4 antagonist, LY290154
-
Several novel approaches have been investigated for the synthesis of the LTD4/E4 antagonist LY290154. Significant improvements to the discovery route were first made by using an indoline nucleophile instead of an indolyl anion in the key substitution step. An alternative approach, introducing the 7-chloroquinoline moiety in the latest stages of the synthesis was then demonstrated. Interestingly, the pivotal intermediate of this latter route was also obtained in a one-pot process following a Katritzky methodology. Finally, an asymmetric synthesis offering significant advantages over the enantioselective route reported by McKillop was demonstrated.
- Merschaert, Alain,Boquel, Pascal,Van Hoeck, Jean-Pierre,Gorissen, Hugo,Borghese, Alfio,Bonnier, Benjamin,Mockel, Anne,Napora, Freddy
-
p. 776 - 783
(2012/12/22)
-
- Highly chemoselective reduction using a Rh/C-Fe(OAc)2 system: Practical synthesis of functionalized indoles
-
Here, we report a highly effective and chemoselective method of preparing substituted indoles from (E)-2-nitropyrrolidinostyrenes via hydrogenation in the presence of a rhodium catalyst doped by additives such as Ni(NO 3)2·6H2O, Fe(OAc)2 or Co(acac)3. These hydrogenation conditions may also be applied to other substrates. Aromatic nitro compounds and olefins can be selectively reduced in the presence of aromatic benzyl ethers, aromatic halides and aromatic aldehydes.
- Akao, Atsushi,Sato, Kimihiko,Nonoyama, Nobuaki,Mase, Toshiaki,Yasuda, Nobuyoshi
-
p. 969 - 972
(2007/10/03)
-
- Structure-activity relationship study of novel necroptosis inhibitors
-
Necroptosis is a regulated caspase-independent cell death mechanism that results in morphological features resembling necrosis. It can be induced in a FADD-deficient variant of human Jurkat T cells treated with TNF-α. 5-(1H-Indol-3-ylmethyl)-2-thiohydantoins and 5-(1H-indol-3-ylmethyl)hydantoins were found to be potent necroptosis inhibitors (called necrostatins). A SAR study revealed that several positions of the indole were intolerant of substitution, while small substituents at the 7-position resulted in increased inhibitory activity. The hydantoin ring was also quite sensitive to structural modifications. A representative member of this compound class demonstrated moderate pharmacokinetic characteristics and readily entered the central nervous system upon intravenous administration.
- Teng, Xin,Degterev, Alexei,Jagtap, Prakash,Xing, Xuechao,Choi, Sungwoon,Denu, Regine,Yuan, Junying,Cuny, Gregory D.
-
p. 5039 - 5044
(2007/10/03)
-
- Inhibitors of cellular necrosis
-
The present invention relates to compounds and pharmaceutical preparations and their use in therapy for preventing or treating trauma, ischemia, stroke and degenerative diseases associated with cell death. Methods and compositions of the invention are particularly useful for treating neurological disorders associated with cellular necrosis.
- -
-
Page/Page column 38
(2008/06/13)
-
- (5- (2-PHENYL)-THIAZOL-5-YLMETHOXY)-INDOL-1-YL) -ACETIC ACID DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS OF THE HUMAN PPAR-DELTA RECEPTOR FOR THE TREATMENT OF METABOLIC DISORDERS SUCH AS TYPE 2 DIABETES
-
Disclosed are compounds having the structure of Formula (I) and pharmaceutically acceptable salts and solvates thereof [A]-[B]-[C] (I) wherein (a) [A] is [H]-[L]; wherein [H] represents a CCOH (or a hydrolyzable ester thereof) or tetrazole group [L] is: formula (II), b) [B] is a ring system selected from the group consisting of: e.g. formula (III); (IIIA), c) [C] is e.g. formula (IV); the other substituents and variables are defined in the claims; as modulators of the human PPAR-delta receptor for the treatment of metabolic disorders such as type 2 diabetes.
- -
-
Page/Page column 141
(2008/06/13)
-
- Convenient synthesis of 7-hydroxyindole
-
7-Hydroxyindole, the key building block for the synthesis of AJ-9677 1, was prepared from indoline in six steps in 36% overall yield. AJ-9677 1 is a potent and selective adrenaline β3-agonist being considered as a clinical candidate to treat obesity in those who are suffering from diabetes.
- Ishiyama, Kazunao,Yamada, Yasuhiro
-
p. 1021 - 1022
(2007/10/03)
-
- An improved synthesis of hydroxyindoles
-
An improved synthetic procedure for the synthesis of 6- and 7-hydroxyindoles is described. In this method, the addition of two chlorine atoms in 1-benzyloxy-4,5-dichloro-2-nitrobenzene (3) and 1-benzyloxy-2,6- dichloro-3-nitrobenzene (9) facilitated the subsequent cyanomethylation step to give substituted cyanomethyl-dichloronitrobenzenes 4 and 10, leading to an overall increase in the yield of the hydroxyindoles 6 and 12.
- Lerman, Lena,Weinstock-Rosin, Marta,Nudelman, Abraham
-
p. 3043 - 3046
(2007/10/03)
-
- An efficient and practical synthesis of N,N-diethyl-7-indolyloxyacetamide via 7-hydroxyindole
-
An efficient and practical synthesis of N, N-diethyl-7-indolyloxyacetamide (1) from 3-hydroxy-2-nitrotoluene (4) via 7-hydroxyindole (2) is described. Treatment of 3-benzyloxy-2-nitrotoluene (5) obtained from 4 with DMF dimethyl acetal and pyrrolidine afforded the (E)-2-nitro-β-pyrrolidinostyrene 6, which can be readily converted into the 2-nitrophenylacetaldehyde semicarbazone 7 without isolation of 6. Hydrogenation of 7 over Pd/C, followed by reaction of the resulting 2 with 2-chloro-N, N-diethylacetamide produced 1 in good yield.
- Harada, Hiroshi,Fujii, Akihito,Kato, Shiro
-
p. 507 - 514
(2007/10/03)
-
- Method for dyeing keratinous fibers with indole compounds, compositions and devices for implementation
-
Method for dyeing keratinous fibers, in particular, human keratinous fiber such as hair, without the use of iodide ions wherein a tinctorial composition containing, in a cosmetically acceptable medium having a pH of less than or equal to 7, at least one indole derivative corresponding to the formula in which: R1denotes hydrogen, alkyl or COOH; R2denotes hydrogen or alkyl; R denotes hydrogen, Si(CH3)3, or COalkyl; and X denotes hydrogen, OH, or OSi(CH3)3; it being possible for X in the 4- or 5-position also to denote the O-alkyl group, on condition that when X is in the 5-position with the meanings mentioned above and OR denotes OH in the 4- or 6-position, only one of the group R1and R2then differs from hydrogen; that when X denotes hydrogen, OR must be in the 7-position and R2must denote hydrogen; and that when R denotes hydrogen and X denotes OH, OR and X are then in the 5- and the 6-position and R1denotes COOH, to the fibers in a first step and, after a dwell time followed by rinsing and rubbing dry, applying an alkaline oxidizing solution.
- -
-
-
- Process for the preparation of indole compounds
-
The present invention relates to a novel process for the preparation of a monohydroxyindole or dihydroxyindole compound by a single step of placing in contact, in a solvent medium, at least one hydrolase with at least one indole compound bearing one or two radicals connected by an ester function to the benzene ring.
- -
-
-
- Product based on inorganic or organic lamellar particles, containing a melanotic pigment, process for preparing it and its use in cosmetics
-
The invention relates to a product in powder form consisting of organic or inorganic particles having a lamellar structure, having a size of less than 50 microns and containing at least one synthetic melanotic pigment formed in situ by oxidation of an indole compound, and to its use for the protection of the human epidermis, in make-up products and for dyeing hair.
- -
-
-
- Process for dyeing keratin fibres with a monohydroxyindole associated with an iodide and hydrogen peroxide
-
Process for dyeing keratin fibres consisting in applying on these fibres a composition (A) containing at least one indole colorant of formula: STR1 where R1 =H or C1 -C4 alkyl; R2 and R3, which may be identical or different, denote H, C1 -C4 alkyl, carboxyl or alkoxycarbonyl; or a salt or a precursor of a compound (I), associated, either with iodide ions, or with H2 O2 ; application of composition (A) being preceded or followed by the application of a compound (B) which contains, either H2 O2 at a pH of 2 to 12 when (A) contains iodide ions, or iodide ions at a pH of 2 to 11 when (A) contains H2 O2. This process allows particularly powerful and resistant dyes to be made.
- -
-
-
- Process for dyeing keratinous fibres with a hydroxyindole in combination with a quinone derivative; and novel 1,4-benzoquinones
-
Process for dyeing keratinous fibres, comprising the step of applying to these fibres at least one composition A containing, in a medium appropriate for dyeing, at least one mono- or di-hydroxyindole the application of the composition A being preceded or followed by the application of a composition B containing, in a medium appropriate for dyeing, at least one quinone derivative chosen from ortho- or para-benzoquinones, monoimines or diimines of ortho- or para-benzoquinones, 1,2- or 1,4-naphthoquinones, sulphonimides of ortho- or para-benzoquinones, α, ω-alkylene-bis-1,4-benzoquinones, or 1,2- or 1,4-naphthoquinone-monoimines or -diimines; the mono- or di-hydroxyindoles and the quinone derivatives being chosen such that the oxidation-reduction potential difference ΔE between the oxidation-reduction potential Ei of the mono- or di-hydroxyindoles, determined at pH 7 in a phosphate medium on a vitreous carbon electrode by voltametry, and the oxidation-reduction potential Eq of the quinone derivative determined at pH 7 in a phosphate medium by polarography on a mercury electrode and relative to a saturated calomel electrode is such that
- -
-
-
- The synthesis of 7-alkoxyindoles
-
A number of protected 7-hydroxyindoles was prepared by reaction of the protected 2-nitrophenols with vinylmagnesium bromide. Benzhydryl was shown to be the protecting group of choice, giving good yields of the indole and being readily removed for subsequent transformations of the 7-hydroxy function.
- Dobson,Todd,Gilmore
-
p. 611 - 617
(2007/10/02)
-
- Chemo-enzymatic synthesis and characterization of L-tryptophans selectively 13C-enriched or hydroxylated in the six-membered ring using transformed Escherichia coli cells
-
L-(3a-13C)- and L-(6-13C)tryptophan have been synthesized from simple labelled compounds via a single reaction scheme based on the conversion of 1,3-cyclohexanedione into indole.The labelled indoles have been converted in one step into the corresponding L-tryptophans using transformed Escherichia coli cells with large amounts of the enzyme, tryptophan synthease.The same reaction scheme has been used for the synthesis of 4- and 7-indolol.These hydroxyindoles together with 5-indolol have been converted into 4-, 7- and 5-hydroxy-L-tryptophan, respectively, using theEscherichia coli cells.The latter compound is the immediate precursor of the neurotransmitter, serotonin.It appears that 7-indolol is the only indole derivative which is converted faster than unsubstituted indole by the enzyme, tryptophan synthease.With the preparation of L-(3a-13C)- and L-(6-13C)tryptophan, we have completed the series of indoles and L-tryptophans with a stable isotope (13C, 15N or 2H) in the aromatic ring.In this paper, we also discuss the NMR parameters of these mono-isotopically labelled systems.
- Berg, E. M. M. van den,Jansen, F. J. H. M.,Goede, A. T. J. W. de,Baldew, A. U.,Lugtenburg, J.
-
p. 287 - 297
(2007/10/02)
-
- Reactions of Organic Anions, 147.- Simple and General Synthesis of Hydroxy- and Methoxyindoles via Vicarious Nucleophilic Substitution of Hydrogen
-
A simple synthesis of 4-, 5-, 6-, and 7-hydroxy- and -methoxyindoles via cyanoalkylation of O-protected nitrophenols by vicarious nucleophilic substitution of hydrogen, followed by catalytic hydrogenation of the (2-nitroaryl)acetonitriles obtained is described.
- Makosza, Mieczyslaw,Danikiewicz, Witold,Wojciechowski, Krzysztof
-
p. 203 - 208
(2007/10/02)
-
- Benzofuranyl carbamates
-
Compounds of the structure; STR1 and pharmaceutically acceptable salts thereof, wherein: R1 is H, alkyl, alkoxy, carboxyl, alkylcarboxy, trifluoromethyl, halogen, nitro or hydroxy; X is O, N, S or C; Y is O, N or S; and R2 is H, alkyl, cycloalkyl, aryl or heteroaryl useful in the treatment of ischemic heart disease and hypertriglyceridemia.
- -
-
-
