co300122n_si_003.pdf (15.77 MB)
Diversity Oriented Synthesis of a Vinblastine-Templated Library of 7‑Aryl-Octahydroazonino[5,4‑b]indoles via a Three-Component Reaction
journal contribution
posted on 2013-01-14, 00:00 authored by Demosthenes Fokas, Mira Kaselj, Yuko Isome, Zhimin WangA vinblastine-templated library of 7-aryl-octahydroazonino[5,4-b]indoles was prepared by a three-component reaction from
indolizino[8,7-b]indoles, chloroformates, and activated
arenes via a chloroformate mediated fragmentation of the indolizinoindole
nucleus followed by insertion of an activated arene. In addition to
N3-carbamoyl-7-aryl-octahydroazonino[5,4-b]indoles
prepared in one step, a wide range of N3-substituted substrates were
synthesized in one pot via the derivatization of a versatile N3–H-azonino[5,4-b]indole intermediate generated in situ by application of
the same strategy. A subset of 308 compounds out of a virtual library
of 3216, representing 13 different chemotypes, was prepared by high
throughput solution-phase synthesis and subsequently purified by mass-triggered
high performance liquid chromatography (HPLC). A total
of 188 compounds with a minimum purity of 80% by UV214 nm and 85% by evaporative light scattering detection (ELSD) was isolated
for primary screening.