Synthetic Study of Kosinostatin Aglycon: Synthesis of the ABCDEFG Ring Skeleton

A synthetic method for the CDEFG substructure of kosinostatin was developed using the cyclization of the di-<i>para</i>-nosyl 3-(2-hydroxyethyl)pyrrolidin-2-imine derivative. The key to the success of this cyclization was the choice of the <i>para</i>-nosyloxy (<i>p</i>-NsO) group as the leaving group. This selection enabled the cyclization to proceed under mild reaction conditions, leading to the first construction of a kosinostatin-type scaffold. The method was further applied to the synthesis of the ABCDEFG ring of kosinostatin aglycon.