734534-08-8Relevant articles and documents
Synthesis and Biological Evaluation of Endocannabinoid Uptake Inhibitors Derived from WOBE437
M?der, Patrick,Bartholom?us, Ruben,Nicolussi, Simon,Baumann, Alice,Weis, Melanie,Chicca, Andrea,Rau, Mark,Sim?o, Ana Catarina,Gertsch, Jürg,Altmann, Karl-Heinz
, p. 145 - 154 (2020/06/02)
WOBE437 ((2E,4E)-N-(3,4-dimethoxyphenethyl)dodeca-2,4-dienamide, 1) is a natural product-derived, highly potent inhibitor of endocannabinoid reuptake. In this study, we synthesized almost 80 analogues of 1 with different types of modifications in the dodecadienoyl domain as well as the dimethoxyphenylethyl head group, and we investigated their effects on anandamide uptake into U937 cells. Intriguingly, none of these analogues was a more potent inhibitor of anandamide uptake than WOBE437 (1). At the same time, a number of WOBE437 variants exhibited potencies in the sub-100 nM range, with high selectivity over inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase; two compounds were virtually equipotent with 1. Interestingly, profound activity differences were observed between analogues in which either of the two methoxy substituents in the head group had been replaced by the same bulkier alkoxy group. Some of the compounds described here could be interesting departure points for the development of potent endocannabinoid uptake inhibitors with more drug-like properties.
Development of an Efficient Synthesis of rac-3-Demethoxyerythratidinone via a Titanium(III) Catalyzed Imine-Nitrile Coupling
Luu, Hieu-Trinh,Streuff, Jan
, p. 139 - 149 (2019/01/04)
We herein describe the evolution of a rapid, high-yielding synthesis of the erythrina alkaloid 3-demethoxyerythratidinone. The natural product is assembled in six steps from commercial precursors in 30–35 % overall yield and with only two chromatographical purification operations. The key step is a titanium(III) catalyzed umpolung reaction in form of a reductive imine–nitrile coupling that can be combined with a subsequent cyclization reaction on a 50 mmol scale. Furthermore, optimized Wacker oxidation conditions enable the selective alkene oxidation in the presence of a tertiary amine functionality, which has been a problem in previous syntheses of erythrina alkaloids. The racemic route can be used to prepare the natural product on gram scale and the results may be useful for the synthesis of related alkaloids.
A Titanium(III)-Catalyzed Reductive Umpolung Reaction for the Synthesis of 1,1-Disubstituted Tetrahydroisoquinolines
Luu, Hieu-Trinh,Wiesler, Stefan,Frey, Georg,Streuff, Jan
, p. 2478 - 2481 (2015/05/27)
A catalytic reductive C1-acylation of 3,4-dihydroisoquinolines is presented that gives direct access to 1,1-disubstituted tetrahydroisoquinolines. The reaction is a titanium(III)-catalyzed reductive umpolung process in which nitriles act as effective acylation agents. The method is highly chemo- and regioselective and is demonstrated in 20 examples. It is well-suited for the large-scale synthesis of functionalized tetrahydroisoquinoline products, which is exemplified in the form of a six-step synthesis of (±)-3-demethoxyerythratidinone. (Figure Presented).
Synthesis and structure-activity relationship of disubstituted benzamides as a novel class of antimalarial agents
Mitachi, Katsuhiko,Salinas, Yandira G.,Connelly, Michele,Jensen, Nicholas,Ling, Taotao,Rivas, Fatima
supporting information; scheme or table, p. 4536 - 4539 (2012/08/07)
Malaria is a devastating world health problem. Using a compound library screening approach, we identified a novel series of disubstituted benzamide compounds with significant activity against malaria strains 3D7 and K1. These compounds represent a new antimalarial molecular scaffold exemplified by compound 1, which demonstrated EC50 values of 60 and 430 nM against strains 3D7 and K1, respectively. Herein we report our findings on the efficient synthesis, structure-activity relationships, and biological activity of this new class of antimalarial agents.
Concise synthesis of the erythrina alkaloid 3-demethoxyerythratidinone via combined rhodium catalysis
Joo, Jung Min,David, Ramoncito A.,Yuan, Yu,Lee, Chulbom
supporting information; experimental part, p. 5704 - 5707 (2011/03/19)
The total synthesis of the erythrina alkaloid 3-demethoxyerythratidinone has been achieved via a strategy based on combined rhodium catalysis. The catalytic tandem cyclization effected by the interplay of alkynyl and vinylidene rhodium species allows for
A novel approach to the bridged indole alkaliods
El Bialy, Serry A. A.
, p. 415 - 434 (2007/10/03)
Access to the bridged indole alkaloids using 1,5-radical translocation and cyclization reactions was discovered. Radicals derived from (o-iodobenzoyl)- tetrahydroisoquinoline substituted with 1-[3-(trimethylsilyl)prop-2-ynyl] or 1-[4-(trimethylsilyl)but-3
