Ionic-Liquid-Catalyzed Access to CTr: An Antitumor Agent

Abstract

b:4,5-b′:7,8-b″]triindole) is a unique 9-membered indole-fused cycloalkane alkaloid with improved druglike privilege and therapeutic potential, but its supply issue remains unsolved, which thus restrains its further exploration. Here, using [EMIm]-[HSO 4 ] as catalyst and solvent, we present an efficient synthesis of CTr from 3-[(phenylmethoxy)methyl]-1H-indole (O-Bn-I3C) which is readily prepared from indole-3-carbinol (I3C). The multiple H-bonding interactions of O-Bn-I3C with [EMIm]-[HSO 4 ] were evidenced to play decisive roles in the selective construction of CTr. The approach is selective, sustainable, scalable, and easy-to-handle, thereby serving as a reliable access to the alkaloid. The amply afforded CTr sample allowed us to investigate its solvent-dependent conformational preference and its spectrum of antitumor activity, pinpointing that CTr is also active against human osteosarcoma cell line H2OS with an IC 50 value of 1.0 μM. In aggregation, the work uncovers the catalytic feature and prowess of [EMIm][HSO 4 ] and establishes the efficient synthesis of CTr, thereby extending the application of the multiple H-bonding catalysis over ionic liquid and facilitating further development of this structurally intriguing therapeutic candidate.

Verification of preparations of (1H-indol-3-yl)methyl electrophiles and development of their microflow rapid generation and substitution

“…However, this approach suffers from the requirement of high temperatures and long reaction times, as well as limited substrate scope 6 – 9 . In addition, highly electrophilic vinyl iminium intermediate 2 is gradually generated; therefore, the resultant coexistence of substrate 1 and electrophile 2 leads to undesired dimerization and/or oligomerization 6 – 13 . Although the rapid generation of 2 from highly reactive (1 H -indol-3-yl)methyl electrophiles 6 containing good leaving groups (Y = halogen, OSO 2 R) can potentially avoid the undesired dimerization/oligomerization, they have been rarely used in the substitution reactions at the 3’-position of the electron-rich indoles (Fig.…”

Preparation of Core/Shell Fe3O4@SiO2 ⋅ DIL as a Magnetically Separable Catalyst for the Synthesis of 1, 8‐Dioxodecahydroacridine

“…Ionic liquids (ILs) are one of the most rapidly flourishing areas in different scientific and industrial fields investigated in the past few years. [26][27][28] They have been widely applied in separation process, material science, catalysis, biocatalysis, sensoristics, organic synthesis, medicine, chemical engineering, and as alternatives to hazardous and volatile materials, [29][30][31][32][33][34] because they possess a number of unique properties such as negligible vapor pressure, high thermal, chemical stability, wide liquid range, and no flammability. Moreover, by changing the cation, anion, or alkyl substituents on the cation the physical and chemical properties can be tuned to some extent.…”

Preparation of core/shell Fe3O4@SiO2 .DIL as a magnetically heterogeneous catalyst for the synthesis of 1, 8‐dioxodecahydroacridine

“…Consequently, it is of great interest to develop an e cient and heterogeneous method for the preparation of these important heterocyclic molecules. Ionic liquids (ILs) are one of the most rapidly ourishing areas in different scienti c and industrial elds investigated in the past few years [26-28] .They have been widely applied in separation process, material science, catalysis, biocatalysis, sensoristics, organic synthesis, medicine, chemical engineering, and as alternatives to hazardous and volatile materials [29][30][31][32][33][34], because they possess a number of unique properties such as negligible vapor pressure, high thermal, chemical stability, wide liquid range, and no ammability. Moreover, by changing the cation, anion, or alkyl substituents on the cation the physical and chemical properties can be tuned to some extent [35][36][37].…”