Synthetic Studies towards Pyrido[1,2-a]azepine Stemona Alkaloids

Abstract

The carbon skeleton of the Stemona alkaloids stemokerrin and cochinchistemonine was assembled from three building blocks (a piperidine, a furan, and a tetronate). Key steps linking the fragments included a Stille cross-coupling (piperidine/furan) and an aldol type addition of a tetronate. The furan served as a latent 1,4-difunctional compound which was converted to a γ-ketolactone by a type II photooxygenation. Attempts to construct the C12-C13 double bond of stemokerrin by a late stage oxidation or by an elimination remained unsuccessful. The non-natural products dihydrostemokerrin and furostemokerrin were obtained instead.

The Kornblum DeLaMare rearrangement in natural product synthesis: 25 years of innovation

“…In an attempt to synthesise stemokerrin, a natural product of the pyrido[1,2- a ]azepine subset of Stemona alkaloids, Morgenstern et al employed a KDM rearrangement in the latter half of their synthesis (Scheme 30). 120 The peroxide intermediate was generated from furan 171 and quenched in situ by i-Pr 2 NEt, in this case the regioselectively of the KDM rearrangement was due to the availability of a single H-atom. The γ-hydroxybutenolide 172 was then taken forward in their attempts to synthesise 70 and ultimately resulted in 2 non-natural products; dihydrostemokerrin 175 and furostemokerrin 176 , when attempts to construct the C12–C13 double bond of 174 proved unsuccessful.…”

Strategies for the synthesis ofStemonaalkaloids: an update

“…108 However, no stemocurtisine alkaloids have succumbed to synthesis. The groups of Pyne 109 and Bach 110 have prepared relevant advanced intermediates in independent efforts toward these targets. The Pyne group have a longstanding interest in Stemona alkaloids, 111 and reported their second-generation approach to the stemocurtisine core in 2015 (Scheme 19A).…”