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, and haematocin and discovery of new antiviral and antimalarial agents

K. C. Nicolaou, Min Lu, Sotirios Totokotsopoulos, Philipp Heretsch, Denis Giguère, Ya Ping Sun, David Sarlah, Thu H. Nguyen, Ian C. Wolf, Donald F. Smee, Craig W. Day, Selina Bopp, Elizabeth A. Winzeler

Research output: Contribution to journalArticlepeer-review

Abstract

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).

Original languageEnglish (US)
Pages (from-to)17320-17332
Number of pages13
JournalJournal of the American Chemical Society
Volume134
Issue number41
DOIs
StatePublished - Oct 17 2012
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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