Enantioselective total synthesis of virosaine A and bubbialidine

Abstract

The first enantioselective total syntheses of virosaine A and bubbialidine are described. Key transformations include the formation of a tetracyclic intermediate via an intramolecular aza-Michael addition, generation of a N-hydroxy-pyrrolidine through a Cope elimination and an intramolecular [1,3]-dipolar cycloaddition to generate a complex 7-oxa-1-azabicyclo[3.2.1]octane ring system.

Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

“…An oxidation of the tertiary amine moiety of the securinega precursors would yield the N-oxide derivative I that serves as ab ranching point to various highoxidation-state securinega alkaloids.F or example,aMeisenheimer rearrangement of I yields phyllantidine (7). [5] Further oxidation of I to nitrone II and subsequent 1,3-dipolar cycloaddition reactions yield flueggine A( 8), [6,7] and virosaines A(9) [8,9] and B (10). [6] Other important yet unexplored modes of diversification stem from the enamine III.N atural products such as securingine D( 11), secu'amamine A( 12), fluvirosaones A( 13)a nd B ( 14), flueggeacosine A( 15), and suffruticosine (16)a re presumed to be derived from III.…”

Hughes and Gleason's Virosaine A—Appreciating the Art in Synthesis

“…N‐oxidation of (+)‐allonorsecurinine permitted a tandem [2,3]‐Meisenheimer/[1,3]‐sigmatropic rearrangement, thus disposing the molecule for a presumed biomimetic 1,3‐dipolar cycloaddition to furnish 2 . Only months later, the group of Gademann reported their insightful synthesis of 1 . Much like the strategy of Li et al., their plan entailed the installation of all requisite functionality followed by a late‐stage 1,3‐dipolar cycloaddition to complete the synthesis (Scheme a).…”

The Securinega Alkaloids

“…In the same way, the pentacyclic alkaloid virosaine A (38) might likely derive from bubbialidine (41) and therefore access to virosaine A (38) from bubbialidine ( the oxazine ring (Scheme 40). 79 The latter step was previously explored by Yang and Li for the enantioselective synthesis of virosaine B (39) and flueggine A (46) (vide supra). The synthesis started with commercial 1,4-cyclohexadiene (239), which was easily desymmetrized by an epoxidation reaction and further functionalized to give cyanoacetic acid ester 240 as a racemic mixture.…”