58550-81-5Relevant academic research and scientific papers
Facile Installation of 2-Reverse Prenyl Functionality into Indoles by a Tandem N-Alkylation-Aza-Cope Rearrangement Reaction and Its Application in Synthesis
Chen, Xiaobei,Fan, Huaqiang,Zhang, Shilei,Yu, Chenguang,Wang, Wei
, p. 716 - 723 (2016/01/12)
An unprecedented tandem N-alkylation-ionic aza-Cope (or Claisen) rearrangement-hydrolysis reaction of readily available indolyl bromides with enamines is described. Due to the complicated nature of the two processes, an operationally simple N-alkylation and subsequent microwave-irradiated ionic aza-Cope rearrangement-hydrolysis process has been uncovered. The tandem reaction serves as a powerful approach to the preparation of synthetically and biologically important, but challenging, 2-reverse quaternary-centered prenylated indoles with high efficiency. Notably, unusual nonaromatic 3-methylene-2,3-dihydro-1H-indole architectures, instead of aromatic indoles, are produced. Furthermore, the aza-Cope rearrangement reaction proceeds highly regioselectively to give the quaternary-centered reverse prenyl functionality, which often produces a mixture of two regioisomers by reported methods. The synthetic value of the resulting nonaromatic 3-methylene-2,3-dihydro-1Hindole architectures has been demonstrated as versatile building blocks in the efficient synthesis of structurally diverse 2-reverse prenylated indoles, such as indolines, indolefused sultams and lactams, and the natural product bruceolline D.
Fluorination Patterning: A Study of Structural Motifs That Impact Physicochemical Properties of Relevance to Drug Discovery
Huchet, Quentin A.,Kuhn, Bernd,Wagner, Bj?rn,Kratochwil, Nicole A.,Fischer, Holger,Kansy, Manfred,Zimmerli, Daniel,Carreira, Erick M.,Müller, Klaus
, p. 9041 - 9060 (2015/12/08)
The synthesis of a collection of 3-substituted indole derivatives incorporating partially fluorinated n-propyl and n-butyl groups is described along with an in-depth study of the effects of various fluorination patterns on their properties, such as lipophilicity, aqueous solubility, and metabolic stability. The experimental observations confirm predictions of a marked lipophilicity decrease imparted by a vic-difluoro unit when compared to the gem-difluoro counterparts. The data involving the comparison of the two substitution patterns is expected to benefit molecular design in medicinal chemistry and, more broadly, in life as well as materials sciences.
Dearomative indole [5+2] cycloaddition reactions: Stereoselective synthesis of highly functionalized cyclohepta[b]indoles
Mei, Guangjian,Yuan, Hao,Gu, Yueqing,Chen, Wei,Chung, Lung Wa,Li, Chuang-Chuang
, p. 11051 - 11055 (2015/03/30)
The first dearomative indole [5+2] cycloaddition reaction with an oxidopyrylium ylide resulted in efficient and diastereoselective construction of some highly functionalized and synthetically challenging oxacyclohepta[b]indoles. The protocol proceeds unde
Monatin, its stereoisomers and derivatives: Modeling the sweet taste chemoreception mechanism
Bassoli, Angela,Borgonovo, Gigliola,Busnelli, Gilberto,Morini, Gabriella,Merlini, Lucio
, p. 2518 - 2525 (2007/10/03)
The sweet natural compound monatin 1 has two stereogenic centers, and the 2S,4S absolute configuration has been attributed previously to the natural isomer. Among the four stereoisomers of monatin, three of them, particularly the 2R,4R isomer, tastes intensely sweet. The conformations of the four compounds have been studied by means of molecular modelling techniques. Both the diastereoisomeric forms show strong intramolecular hydrogen bonds which involve different functional groups and give rise to two different minimum energy conformations. The tertiary alcohol group in monatin seems to be indirectly involved in the generation of the taste, acting as an important contraint in generating the active conformation. The most important glucophores have been identified in the terminal -NH3+ and -COO - groups and in the indole ring by comparison with known topological models of sweet compounds and through the synthesis of appropriate derivatives in which some of these groups are lacking or modified. The relative affinity of each stereoisomer for its putative sweet taste receptor has been estimated semi-quantitatively with the pseudoreceptor modelling technique. The predicted activity calculated with this technique is in good agreement with the experimental data and explains why the 2R,4R isomer (and not the natural 2S,4S isomer) is the sweetest of the series. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
3-(Azolylmethyl)-1H-indoles as selective P450 aromatase inhibitors
Marchand,Le Borgne,Duflos,Robert-Piessard,Le Baut,Ahmadi,Hartmann,Palzer
, p. 211 - 218 (2007/10/03)
The synthesis of 1-(halobenzyl) and 1-tosyl-3-(1H-imidazol-1-ylmethyl)-1H-indoles, 1-(halobenzyl) and 1-tosyl-3-(1H-1,2,4-triazol-1-ylmethyl)-1H-indoles and 1-(halobenzyl)-3-(4H-1,2,4-triazol-4-ylmethyl)-1H-indoles is described. 3-(Azolylmethyl)-1H-indoles were obtained in three steps from 1H-indole-3-carbaldehyde (1) by benzylation or tosylation, reduction and azole moiety fixation. In an alternative method, the bromo intermediates issued from the corresponding alcohols were condensed with the azolium sodium salts. Inhibitory activity against P450(arom) and P450(17α), and influence on retinoic acid metabolism were evaluated. Three imidazole compounds exhibited potent and selective aromatase inhibitory activity.
