- An alternative approach to the synthesis of anticancer molecule spirobrassinin and its 2′-amino analogues
-
Abstract: A convenient synthesis of the cruciferous phytoalexin (S)-(?)-spirobrassinin and its (±)-2′-amino analogues have been achieved. Our synthetic route towards (S)-(?)-spirobrassinin is based on the CrO3-mediated cyclization of chiral 1-(2′,3′,4′,6′-tetra-O-acetyl-?-D-glucopyranosyl)brassinin and subsequent removal of the chiral auxiliary. (±)-2′-Amino analogues of spirobrassinin and 1-methoxyspirobrassinin were obtained from thioureas in one step in an efficient manner with the aid of CrO3. New synthesized compounds were screened in vitro for antiproliferative/cytotoxic activity against six human cancer cell lines by MTT assay. Amino analogues with CF3 functionality displayed good antiproliferative effect. Graphic abstract: [Figure not available: see fulltext.].
- Budovská, Mariana,Tischlerová, Viera,Moj?i?, Ján,Kozlov, Oleksandr,Gondová, Ta?ána
-
-
Read Online
- Orthogonal Syntheses of γ-Carbolinone and Spiro[pyrrolidinone-3,3′]indole Derivatives in One Pot through Reaction Telescoping
-
Herein we report a series of telescoping methodologies for one pot synthesis of biologically relevant γ-carboline derivatives 6 and spiro[pyrrolidinone-3,3′]indole 7. Initially the three consecutive steps of cyclopropanation, phthalimide deprotection, and Boc-deprotection have been congregated in a single reaction vessel to afford a ～1:1 mixture of 6 and 7. Next, careful optimization of the reaction sequence and the conditions generated an orthogonal approach to access compounds 6 and 7 exclusively. Air oxidation of the γ-carbolinones 6 afforded aromatic γ-carbolines 8.
- Guha, Souvik,Gadde, Satyanarayana,Kumar, Naresh,Black, David Stclair,Sen, Subhabrata
-
-
Read Online
- A concise synthesis of cyclobrassinin and its analogues via a thiyl radical aromatic substitution
-
A simple and concise approach for the synthesis of cyclobrassinin has been developed through a thiyl radical-mediated intramolecular aromatic substitution, with benzoyl peroxide as an efficient initiator and oxidant. The current method can also be utilized in the synthesis of 6 and 7-membered ring cyclobrassinin analogues in moderate to good yields. The transformation involves a formal radical 6 and 7-endo-trig cyclization of the corresponding dithiocarbamate derivatives, which were generated from indole-3-methanamines and tryptophan.
- Zhong, Xin,Chen, Ning,Xu, Jiaxi
-
supporting information
p. 13549 - 13557
(2018/08/21)
-
- SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
-
The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer, wherein A, R2, R3, R10, E1, E2, E3, Y, and Z are as defined herein.
- -
-
Page/Page column 256
(2017/08/01)
-
- Screening of NOS activity and selectivity of newly synthesized acetamidines using RP-HPLC
-
Nitric Oxide Synthase (NOS) inhibitors could play a powerful role in inflammatory and neurodegenerative diseases. In this work, novel acetamidine derivatives of NOS were synthesized and the inhibitor activity was evalued. To screen the activity and selectivity, the l-citrulline residue, after the enzymatic NOS assay, was derivatized with o-phthaldialdehyde/N-acetyl cysteine (OPA/NAC) and then evaluated by RP-HPLC method with fluorescence detection.All compounds did not affect the activity of endothelial and neuronal isoforms, while nine of them possessed a percentage of iNOS activity at 10 μM lower than 50%, and were selected for IC50 evaluation. Among them, a compound emerged as a very potent (IC50 of 53 nM) and selective iNOS inhibitor.
- Fantacuzzi, Marialuigia,Maccallini, Cristina,Di Matteo, Mauro,Ammazzalorso, Alessandra,Bruno, Isabella,De Filippis, Barbara,Giampietro, Letizia,Mollica, Adriano,Amoroso, Rosa
-
p. 419 - 424
(2016/02/16)
-
- A novel palladium-catalyzed cyclization of indole phytoalexin brassinin and its 1-substituted derivatives
-
A novel simple synthetic approach to spiroindoline phytoalexins and their derivatives has been developed. The spirocyclization of brassinin and its 1-substituted derivatives was achieved using palladium catalyst PdCl 2(CH3CN)2 in DMSO at 80°C in the presence of water, methanol or aniline.
- Budovska, Mariana
-
p. 5575 - 5582
(2014/01/23)
-
- Novel IDO inhibitors and methods of use thereof
-
Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.
- -
-
Page/Page column 7
(2010/11/27)
-
- Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors
-
A screen of indole-based structures revealed the natural product brassinin to be a moderate inhibitor of indoleamine 2,3-dioxygenase (IDO), a new cancer immunosuppression target. A structure-activity study was undertaken to determine which elements of the brassinin structure could be modified to enhance potency. Three important discoveries have been made, which will impact future IDO inhibitor development: (i) The dithiocarbamate portion of the brassinin lead is a crucial moiety, which may be binding to the heme iron of IDO; (ii) an indole ring is not necessary for IDO inhibition; and (iii) substitution of the S-methyl group of brassinin with large aromatic groups provides inhibitors that are three times more potent in vitro than the most commonly used IDO inhibitor, 1-methyl-tryptophan.
- Gaspari, Paul,Banerjee, Tinku,Malachowski, William P.,Muller, Alexander J.,Prendergast, George C.,DuHadaway, James,Bennett, Shauna,Donovan, Ashley M.
-
p. 684 - 692
(2007/10/03)
-
- Synthesis of thiazino[6,5-b]indole derivatives, analogues of the phytoalexin cyclobrassinin. A new method for preparation of 3-aminomethylindole
-
An efficient non-reductive synthesis of 3-aminomethylindole (6) was developed from gramine (1) via 3-phthalimidomethylindole (2). The reactions of amine 6 with substituted methyl dithiobenzoates gave 3- (arylthiocarbonylaminomethyl)indoles. The Hugerschoff ring-closure reactions of the thiobenzamide intermediates (11a-f) with phenyltrimethylammonium tribromide and subsequent basic treatment furnished 2-arylthiazino[6,5-b]indole derivatives (14a-f). By use of the latter bromine source, the phytoalexin cyclobrassinin (8) was prepared in a considerably higher yield than described previously. The structures of the novel products were elucidated by IR, 1H and 13C NMR spectroscopy, including 2D-HMQC, 2D-HMBC and DEPT measurements.
- Csomós, Péter,Fodor, Lajos,Sohár, Pál,Bernáth, Gábor
-
p. 9257 - 9262
(2007/10/03)
-
- New syntheses of indole phytoalexins and related compounds
-
Synthesis of indole phytoalexins brassinin, brassitin, cyclobrassinin and related compounds via 3-aminomethylindole and its 1-substituted derivatives obtained by nickel boride catalyzed reduction of corresponding aldoximes with sodium borohydride and via [1-(t-butoxycarbonyl)-indol-3-yl]methyl isothiocyanate, the first stable derivative of indol-3-ylmethyl isothiocyanate is described. Antifungal activity of the prepared compounds was examined by using the fungus Bipolaris leersiae by t.l.c. bioassay and quantitative screening was carried out with the selected compounds.
- Kutschy, Peter,Dzurilla, Milan,Takasugi, Mitsuo,Toeroek, Marcel,Achbergerova, Ingrid,Homzova, Renata,Racova, Maria
-
p. 3549 - 3566
(2007/10/03)
-
- Indole derivatives with antimycobacterial activity
-
1,3-Dinitro-2-(indol-3'-yl)-propanes 3 are synthesized by Michael reaction of nitromethane with the indolylnitroethenes 2. - Reaction of the aldehydes 4 and 10 with the benzylamines 12 as well as the reaction of the indolylalkylamines 6a and 9a with the benzaldehydes 11 lead to Schiff bases which are reduced to N-benzyl-(indol-3-ylmethyl)-amines 13 and N-benzyl-(indol-3-ylethyl)-amines 14, respectively; tert amines 16 are synthesized via the formamides 15, amines 18 are prepared according to Mannich. - Inhibitory effects on Mycobacterium tuberculosis H 37 Ra are investigated, a structure-activity relationship is discussed.
- Mahboobi,Grothus,Meindl
-
p. 105 - 114
(2007/10/02)
-
- A SYNTHESIS METHOD OF INDOLE-3-METHANAMINE AND/OR GRAMINE FROM INDOLE-3-CARBOXALDEHYDE, AND ITS APPLICATION FOR THE SYNTHESES OF BRASSININ, ITS 4-SUBSTITUTED ANALOGS, AND 1,3,4,5-TETRAHYDROPYRROLOQUINOLINE
-
Simple conversion method of indole-3-carboxaldehyde into gramine and/or indole-3-methanamine was developed.The present method realized short step syntheses of brassinin, 4-iodo-, methoxy-, 4-methoxy, and 4-nitrobrassinin, 4-methoxyindole-3-acetonitrile, and 1,3,4,5-tetrahydropyrroloquinoline.
- Yamada, Fumio,Kobayashi, Kensuke,Shimizu, Aya,Aoki, Naokatsu,Somei, Masanori
-
p. 2783 - 2804
(2007/10/02)
-
- A SIMPLE SYNTHESIS OF A PHYTOALEXIN, METHOXYBRASSININ
-
A simple and an alternative multi-gram scale synthetic method methoxybrassinin is developed starting from indole-3-carboxaldehyde.
- Somei, Masanori,Kobayashi, Kensuke,Shimizu, Kazuhisa,Kawasaki, Toshiya
-
-
- THE FIRST TOTAL SYNTHESES OF 9-METHOXYCARBAZOLE-3-CARBOXALDEHYDE AND METHOXYBRASSININ (THE CHEMISTRY OF 1-METHOXYINDOLE)
-
The first total syntheses of an alkaloid 9-methoxycarbazole-3-carboxaldehyde and a phytoalexin methoxybrassinin are reported.
- Kawasaki, Toshiya,Somei, Masanori
-
p. 1605 - 1608
(2007/10/02)
-
- AN INTRAMOLECULAR PHOTOCYCLIZATION TO FORM THE AZEPINOINDOLE SYSTEM
-
Azepinoindoles 5a and 5b are formed in good yield via the intramolecular photocyclization of N-chloroacetyl-3-aminomethylindoles.
- Klohr, Steven E.,Cassady, John M.
-
p. 671 - 674
(2007/10/02)
-
- Simple Syntheses of 3-Substituted Indoles and their Applications for High Yield 14C-Labelling
-
Methods are described which allow the synthesis of several plant indole alkaloids and their metabolites at different scales.Compounds synthesized include gramine (1) (3-dimethylaminoindole) which is directly derived from indole, while its biosynthetic precursor 3-aminomethylindole (3) and 3-methylaminomethylindole (2) as well as indole-3-carboxylic acid (7) are synthesized via indole-3-aldehyde (6).Slight changes of the experimental conditions allow syntheses with high yields not only at the molar but also at the μmolar level.This is extremely useful when isotope labelled compounds of high specific radioactivity are required for studies of plant metabolism. - Keywords: 3-Substituted Indoles, Indole Alkaloids, UV Spectra, MS Spectra, 1H NMR spectra
- Schallenberg, Juergen,Meyer, Eckart
-
p. 108 - 112
(2007/10/02)
-
