Synthesis and Biological Evaluation of CF₃Se‐Substituted α‐Amino Acid Derivatives

Abstract

Several CF3Se‐substituted α‐amino acid derivatives, such as (R)‐2‐amino‐3‐((trifluoromethyl)selanyl)propanoates (5 a/6 a), (S)‐2‐amino‐4‐((trifluoromethyl)selanyl)butanoates (5 b/6 b), (2R,3R)‐2‐amino‐3‐((trifluoromethyl)selanyl)butanoates (5 c/6 c), (R)‐2‐((S)‐2‐amino‐3‐phenylpropanamido)‐3‐((trifluoromethyl)selanyl)propanoates (11 a/12 a), and (R)‐2‐(2‐aminoacetamido)‐3‐((trifluoromethyl)selanyl)propanoates (11 b/12 b), were readily synthesized from natural amino acids and [Me4N][SeCF3]. The primary in vitro cytotoxicity assays revealed that compounds 6 a, 11 a and 12 a were more effective cell growth inhibitors than the other tested CF3Se‐substituted derivatives towards MCF‐7, HCT116, and SK‐OV‐3 cells, with their IC50 values being less than 10 μM for MCF‐7 and HCT116 cells. This study indicated the potentials of CF3Se moiety as a pharmaceutically relevant group in the design and synthesis of novel biologically active molecules.

Trifluoromethyl Selenoxides: Electrophilic Reagents for C–H Trifluoromethylselenolation of (Hetero)Arene

“…Among the fluorine-containing groups, the trifluoromethylselenyl group (CF 3 Se) is an emerging fluorinated moiety and has attracted increasing attention because it has a relatively high Hansch lipophilicity parameter (Hansch–Leo Parameter π R = 1.61) , and strong electron-withdrawing effect (Hammett constants σ m = 0.44, σ p = 0.45) , As we know, selenium (Se) is an essential trace element in the human body as a vital part of antioxidant enzymes that protect cells against the effects of free radicals produced during metabolism . Moreover, though there are no CF 3 Se-containing drugs or agrochemicals yet, recent investigations have demenstrated that trifluoromethylselenolated compounds have a great potential for application in life sciences . In this context, it is highly desirable to develop efficient methods to synthesize CF 3 Se-containing compounds as well as develop new trifluoromethylselenolation reagents …”

Design, Synthesis, and Biological Activities of Novel Phenylpyrazole Derivatives Containing a Trifluoromethylselenyl Moiety

“…Recently, the trifluoromethylselenyl group is generally applied to pharmaceutical research; − the relevant investigation in pesticide has been rarely reported. It has been proved that the combination of Se or SeCF 3 with bioactive molecules may improve the activity and biosafety of these compounds. − The development and exploration of selenium-containing structures may provide new possibilities for the discovery of safe, efficient, and environmentally friendly pesticides (Figure ).…”

Photoinduced Copper-Promoted Decarboxylative Trifluoromethylselenolation of Aromatic Carboxylic Acids with [Me4N][SeCF3]

“…Thanks to the significant electronic characteristics (Hammett constants σ p = 0.45, σ m = 0.44) and the larger Hansch–Leo parameter (π = 1.61) than those of OCF 3 (π = 1.04) and SCF 3 (π = 1.44) groups, the SeCF 3 functionality has been recognized as one of the most privileged structural motifs in the pharmaceutical and agrochemical fields. The recent studies on a series of fresh SeCF 3 -containing bioactive compounds have further strengthened this situation. , Thus, great efforts have been made in the construction of C–SeCF 3 bonds by the development of novel SeCF 3 reagents and trifluoromethylselenolation methodologies. , It should be noteworthy that among the known SeCF 3 sources, tetramethylammonium trifluoromethylselenate ([Me 4 N]­[SeCF 3 ]) has been considered as the more convenient and versatile reagent because it is readily accessible, easy to handle, and thermally stable, possessing rich chemistry, and has contributed heavily to the preparation of diverse SeCF 3 -containing molecules. − At present, the search for efficient methods for the introduction of SeCF 3 group into a wide range of organic scaffolds with [Me 4 N]­[SeCF 3 ] has attracted a great deal of attention, which would undoubtedly benefit to accelerate the practical applications of the trifluoromethylselenylated compounds.…”