Selective syntheses of leuconolam, leuconoxine, and mersicarpine alkaloids from a common intermediate through regiocontrolled cyclizations by Staudinger reactions

Abstract

Selective syntheses of alkaloids bearing distinct core structures were enabled by chemically programmed polycyclizations using water as a switch.

ChemInform Abstract: The Diaza[5.5.6.6]fenestrane Skeleton — Synthesis of Leuconoxine Alkaloids

“…Scheme1.Selectedtransformationso ft he 2,7-seco Aspidosperma alkaloid leuconolam (10). TFA = trifluoroacetica cid;PTSA = p-toluenesulfonic acid.…”

“…In the same year,S toltz and Liang completed [10] the racemic total synthesis of 1, 2, 4, 10,a nd 13,i natotal of 15 steps and 7% overall yield (Scheme 10). The divergenta pproachr elies on carefulc ontrol of the cyclization conditions of diketone 71 in the Staudinger reaction.…”

“…[28] Arbolescine (14)r epresents the first example of a seco-leuconoxine andh as not yet been tackled by total synthesis. [29] Interestingly,t he formation of the leuconoxine carbon skeleton was reported long before its isolation either by oxidative rearrangemento fv incadifformine [30] or by acidt reatment [31, 2b] of leuconolam (10) to produce the 6-chloroleuconoxines ( 16). Likewise, treatment of 10 with bromine furnished 6b,7bdibromoleuconoxine ( 17)i n9 0% yield (Scheme 1).…”

The Diaza[5.5.6.6]fenestrane Skeleton—Synthesis of Leuconoxine Alkaloids

“…In the same year, Stoltz and Liang completed the racemic total synthesis of 1 , 2 , 4 , 10 , and 13 , in a total of 15 steps and 7 % overall yield (Scheme ). The divergent approach relies on careful control of the cyclization conditions of diketone 71 in the Staudinger reaction.…”

“…Due to their high complexity, many of these alkaloids became challenging targets for testing new synthetic strategies and methodology. Among them, the leuconoxine group of Aspidosperma alkaloids has garnered tremendous interest from the global synthetic community, which is reflected by six total syntheses in the last two years by the groups of Zhu, Tokuyama, Dai, Higuchi and Kawasaki, Gaich, and Stoltz and Liang . Leuconoxine ( 1 ), first isolated by Abe and Yamauchi in 1994 from Leuconotis eugenifolius , consists of a pentacyclic structure with three contiguous stereogenic centers including one that is quaternary and a labile aminal function (Figure ).…”