724706-17-6Relevant articles and documents
Design, synthesis, biological evaluation and molecular modelling of substituted pyrrolo[2,1-: A] isoquinolinone derivatives: Discovery of potent inhibitors of AChE and BChE
Parravicini, Oscar,Angelina, Emilio,Spinelli, Roque,Garibotto, Francisco,Siano, álvaro S.,Vila, Laura,Cabedo, Nuria,Cortes, Diego,Enriz, Ricardo D.
, p. 8321 - 8334 (2021/05/21)
We report here the design, synthesis and biological evaluation of a new series of substituted pyrrolo[2,1-a]isoquinolin-3-one derivatives, some of which have strong inhibitory activity against both AChE and BChE enzymes. The design of these new inhibitors was carried out taking rivastigmine as the starting structure. Thus, on the basis of an exhausting molecular modeling study using combined techniques (docking, dynamic molecular simulations and QTAIM calculations), we obtained new ligands possessing stronger inhibitory effects than rivastigmine, the reference compound. QTAIM analysis gave us detailed information about the molecular interactions stabilizing the different ligand-enzyme complexes. These calculations showed the importance of the interaction with the CAS esteratic site for the inhibitory effect of these compounds. Nevertheless, they also indicated that the combination of interactions with CAS and strong interactions with the PAS site might be beneficial for the inhibitory effect.
One-pot chemoenzymatic synthesis of trolline and tetrahydroisoquinoline analogues
Zhao, Jianxiong,Lichman, Benjamin R.,Ward, John M.,Hailes, Helen C.
supporting information, p. 1323 - 1326 (2018/02/14)
Chemoenzymatic reaction cascades can provide access to chiral compounds from low-cost starting materials in one pot. Here we describe one-pot asymmetric routes to tetrahydroisoquinoline alkaloids (THIAs) using the Pictet-Spenglerase norcoclaurine synthase (NCS) followed by a cyclisation, to give alkaloids with two new heterocyclic rings. These reactions operated with a high atom economy to generate THIAs in high yields.
Synthesis of condensed tetrahydroisoquinoline class of alkaloids by employing TfOH-mediated imide carbonyl activation
Selvakumar, Jayaraman,Rao, Ramana Sreenivasa,Srinivasapriyan, Vijayan,Marutheeswaran, Srinivasan,Ramanathan, Chinnasamy Ramaraj
, p. 2175 - 2188 (2015/04/14)
Isoquinoline-based polycyclic lactams such as isoindoloisoquinolinones, pyrroloisoquinolinones, and benzo[a]quinolizinones were successfully assembled from the corresponding imides by using a TfOH-mediated (TfOH = trifluoromethanesulfonic acid) imide carbonyl activation and cyclization strategy. By employing this simple method, the isoquinoline alkaloids crispine A, trolline/oleracein E, and erythrinarbine were successfully synthesized in racemic form. The reaction of unsymmetrical N-phenethylphthalimides with TfOH displayed excellent regioselectivity, which was rationalized by DFT calculations.
Synthesis of new antimicrobial pyrrolo[2,1-a]isoquinolin-3-ones
Moreno, Laura,Parraga, Javier,Galan, Abraham,Cortes, Diego,Cabedo, Nuria,Primo, Jaime
, p. 6589 - 6597,9 (2012/12/12)
The attractive structure of the pyrroloisoquinoline moiety, together with its potential antimicrobial activity, encouraged us to prepare six 8-substituted and seven 8,9-disubstituted-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-3- ones in a few steps with good yields. We applied a convenient methodology via double intramolecular cyclization conducted by a Bischler-Napieralski cyclodehydration-imine reduction sequence, which is widely employed in the synthesis of isoquinoline alkaloids. Therefore, we synthesized three series of these pyrrolo[2,1-a]isoquinolin-3-ones characterized by the substituent at the 8-position or 8,9-positions of the aromatic ring: (a) different side chains are attached to an 8-OH group (series 1); (b) a chlorine atom is attached to the 8-position (series 2); and (c) 8- and 9-carbons are bearing an identical group (series 3). The compounds bearing a benzylic moiety at the 8-position, for example, 8-benzyloxy-pyrrolo[2,1-a]isoquinolin-3-one (1a) and 8-(4-fluorobenzyloxy)-pyrrolo[2,1-a]isoquinolin-3-one (1e), as well as, a 8-chloro-9-methoxy moiety including the 8-chloro-9-methoxy-pyrrolo[2,1-a] isoquinolin-3-one (2a), provided the most fungicide and bactericide agents, respectively.
Stereoselective synthesis of tetrahydroisoquinoline alkaloids: (-)-trolline, (+)-crispin A, (+)-oleracein e
Kawai, Nobuyuki,Matsuda, Mika,Uenishi, Jun'Ichi
, p. 8648 - 8653 (2011/12/01)
Tetrahydroisoquinoline alkaloids, (S)-(-)-trolline, (R)-(+)-crispin A, and (R)-(+)-oleracein E, have been synthesized stereoselectively from the both enantiomers of common intermediate (S)-4 and (R)-4. The key step in the synthesis include a stereoselecti
Iron-catalyzed oxidative coupling of alkylamides with arenes through oxidation of alkylamides followed by Friedel-Crafts alkylation
Shirakawa, Eiji,Uchiyama, Nanase,Hayashi, Tamio
experimental part, p. 25 - 34 (2011/03/22)
FeCl3 in combination with t-BuOOt-Bu as an oxidant was found to be an efficient catalyst for oxidation of alkylamides to α-(tert-butoxy) alkylamides. FeCl2 and CuCl showed, respectively, almost the same and slightly lower activities
Synthesis of (-)-trolline, (-)-crispine A and (-)-crispine E
Kanemitsu, Takuya,Yamashita, Yuki,Nagata, Kazuhiro,Itoh, Takashi
, p. 199 - 203 (2008/09/17)
Biologically active 1-subsutituted tetrahydroisoquinoline alkaloids, (-)-trolline, (-)-crispine A, and (-)-crispine E were synthesized using a chiral isoquinolinecarbaldehyde as a key material. The aldehyde was readily obtained from a 1-cyanoisoquinoline, and subjected to a Horner-Wadsworth-Emmons reaction. The chiral tetrahydroisoquinoline derivative thus obtained was used for the synthesis of the optically active isoquinoline alkaloids.
