Synthesis of monoterpene indole alkaloids, leuconoxine, leuconodine B, and rhazinilam, by transformation of melodinine E via 6-hydro-21-dehydroxyleuconolam was established. The pivotal intermediate, 6-hydro-21-dehydroxyleuconolam, was prepared from melodinine E via a ring-opening N,S-acetal formation of the diaza[5.5.6.6]fenestrane skeleton and subsequent chemoselective reduction. These results demonstrate that 6-hydro-21-dehydroxy-leuconolam is a useful synthetic precursor of these related monoterpene indole alkaloids. © 2020 Elsevier Ltd