Total synthesis of asperdinones B, C, D, E and terezine D

The total synthesis of new members of prenylated indole alkaloids exhibiting α-glucosidase activity is described. Asperdinones B, C, D, and E are characterized by the presence of a (3<i>R</i>)-3-indolylmethylbenzodiazepine-2,5-dione unit at C-3 of C4-C7 prenylated indoles. Methods of direct and indirect prenylation of indole and tryptophan were explored. Different approaches were adopted for the functionalization of C4-C7 prenylindoles at C-3 using Negishi cross-coupling methods. The asperdinones are among the rare tryptophan-derived indole alkaloids which appear to have undergone epimerization due to genetic alteration of specific gene clusters that code for a (3<i>R</i>) configuration.