Total Synthesis of (-)-Acetylaranotin

Epidithiodiketopiperazines are an important class of natural products because of their unique structural and biological properties. Among them, acetylaranotin (1), SCH64874 (2), compound 3, emethallicin A (4), MPC1001 (5), and emestrin (6) feature a dihydrooxepine moiety fused to a pyrrolidine/ epidithiodiketopiperazine (Figure 1). They also display a range of intriguing biological activities, such as: inhibitory activity against viral RNA polymerase, antagonistic activity of epidermal growth factor receptor, potent antituberculous activity, inhibitory activity against histamine release, antiproliferative activity against DU145 human prostate cancer cell line, and antagonistic activity of chemokine receptor (CCR2). While numerous synthetic approaches were investigated, only a limited number of successful preparations of the characteristic dihydrooxepine ring have been reported. During the synthetic studies on MPC1001, Peng and Clive established a synthetic method for a pyrrolidinone-fused dihydrooxepine through tetrahydrooxepine formation followed by selenoxide elimination. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.