11. Synthesis and Biological Evaluation of Epidithio-, Epitetrathio-, and bis-(Methylthio)diketopiperazines: Synthetic Methodology, Enantioselective Total Synthesis of Epicoccin G, 8,8′-epi-ent-Rostratin B, Gliotoxin, Gliotoxin G, Emethallicin E, ...

K.C. Nicolaou, M. Lu, S. Totokotsopoulos, P. Heretsch, D. Giguère, Y.-P. Sun, D. Sarlah, T.H. Nguyen, I.C. Wolf, D.F. Smee, C.W. Day, S. Bopp, E.A. Winzeler— 2012

An improved sulfenylation method for the preparation of epidithio-, epitetrathio-, and bis-(methylthio)diketopiperazines from diketopiperazines has been developed. Employing NaHMDS and related bases and elemental sulfur or bis[bis(trimethylsilyl)amino]trisulfide (23) in THF, the developed method was applied to the synthesis of a series of natural and designed molecules, including epicoccin G (1), 8,8′-epi-ent-rostratin B (2), gliotoxin (3), gliotoxin G (4), emethallicin E (5), and haematocin (6). Biological screening of selected synthesized compounds led to the discovery of a number of nanomolar antipoliovirus agents (i.e., 46, 2,2′-epi-46, and 61) and several low-micromolar anti-Plasmodium falciparum lead compounds (i.e., 46, 2,2′-epi-46, 58, 61, and 1).

Title11. Synthesis and Biological Evaluation of Epidithio-, Epitetrathio-, and bis-(Methylthio)diketopiperazines: Synthetic Methodology, Enantioselective Total Synthesis of Epicoccin G, 8,8′-epi-ent-Rostratin B, Gliotoxin, Gliotoxin G, Emethallicin E, ...
AuthorK.C. Nicolaou, M. Lu, S. Totokotsopoulos, P. Heretsch, D. Giguère, Y.-P. Sun, D. Sarlah, T.H. Nguyen, I.C. Wolf, D.F. Smee, C.W. Day, S. Bopp, E.A. Winzeler
Date2012
IdentifierDOI: 10.1021/ja308429f
Source(s)
CitationJ. Am. Chem. Soc. 2012, 134, 17320-17332