Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells.

Prajwalita Das,Hiroki Doi,Norio Shibata,Hidehiko Akiyama,Etsuko Tokunaga,Norimichi Saito

doi:10.3762/bjoc.14.24

Abstract

Conscious of the potential bioactivity of fluorine, an investigation was conducted using various fluorine-containing diaryliodonium salts in order to study and compare their biological activity against human lymphoma U937 cells. Most of the compounds tested are well-known reagents for fluoro-functionalized arylation reactions in synthetic organic chemistry, but their biological properties are not fully understood. Herein, after initially investigating 18 fluoro-functionalized reagents, we discovered that the ortho-fluoro-functionalized diaryliodonium salt reagents showed remarkable cytotoxicity in vitro. These results led us to synthesize more compounds, previously unknown sterically demanding diaryliodonium salts having a pentafluorosulfanyl (SF5) functional group at the ortho-position, that is, unsymmetrical ortho-SF5 phenylaryl-λ3-iodonium salts. Newly synthesized mesityl(2-(pentafluoro-λ6-sulfanyl)phenyl)iodonium exhibited the greatest potency in vitro against U937 cells. Evaluation of the cytotoxicity of selected phenylaryl-λ3-iodonium salts against AGLCL (a normal human B cell line) was also examined.

Highlights

There has been a surge in the number of reports about fluorine chemistry in recent decades
During our research programs focused on the development of novel reagents for fluoro-functionalization [12,13,16,17,18,19,20,21,22,23], as well as the design and synthesis of biologically active fluorine-containing compounds [24,25,26,27,28], we noted that a series of fluoro-functionalization reagents could themselves be highly potential drug candidates
To begin our investigation related to bioactivity, we randomly selected some fluorinating reagents that we had already developed, including Shibata reagents I [20] and II [21], pentafluorophenylating reagent 2b and several hypervalent iodine reagents, i.e., diaryliodonium salts with a mesitylene ligand (3a–o) and a triisopropylphenyl ligand 4a [20,21,22,59,60,61,62,63,64] (Figure 1)

Summary

Introduction

There has been a surge in the number of reports about fluorine chemistry in recent decades. 19 compounds [20,21,22,59,60,61,62,63,64] were examined for their potential cytotoxicity, and some of them showed potency, in particular ortho-fluoro-functionalized diaryliodonium salts.

Results

Conclusion