Syntheses of Galbulimima Alkaloids

Abstract

The bark of the rain forest tree Galbulimima belgraveana has been identified as a rich source of fascinating natural products and so far 28 unique alkaloids have been isolated. The chemical interest in Galbulimima alkaloids started with the discovery of the promising biological activities of himbacine. Fifteen years after the first total synthesis of himbacine, this class of natural product still inspires, with the structurally more complex congeners himandrine, himgaline, and G.B. 13 as highly challenging synthetic targets. This review article summarizes and discusses all syntheses of Galbulimima alkaloids published to date.

Transition Metal‐Mediated C−C Single Bond Cleavage: Making the Cut in Total Synthesis

“…Theb ark of Galbulimima belgraveana and G. baccata exhibits hallucinogenic effects when chewed, and has been used in traditional medicine in Papua New Guinea, Malaysia, and Northern Australia, where these tropical flowering plants are found. [40] However,t he constituent natural products present in the bark-collectively named the GB alkaloidshave not been extensively tested for their bioactivity,i np art because their complex structures have made their chemical syntheses challenging,l imiting the supply of material for biological study.F or example,t he most concise syntheses of GB alkaloid GB13 (98)r equired 18/19 steps; [41] the related compound GB22 (99)had not been synthesized prior to 2019 (Scheme 14). Here,w ed iscuss the synthesis of GB22 by Shenvi and co-workers,who utilized akey Ir/Ni dual-catalytic siloxycyclopropane C À Cb ond cleavage/arylation that enabled access to GB22 in six steps in the longest linear sequence.…”

Übergangsmetallvermittelte Spaltung von C‐C‐Einfachbindungen

“…Die Rinde von Galbulimima belgraveana und G. baccata hat beim Kauen halluzinogene Wirkung und wird in der traditionellen Medizin in Papua-Neuguinea, Malaysia und Nordaustralien angewendet, wo diese tropischen Pflanzen vorkommen. [40] Allerdings wurden die Naturstoffbestandteile in der Rinde,d ie allgemein als GB-Alkaloide bezeichnet werden, bisher nicht umfassend auf ihre biologische Aktivität untersucht. Grund dafürist teilweise der begrenzte Zugang zu ausreichend Substanz fürbiologische Untersuchungen, da die chemischen Synthesen ihrer komplexen Strukturen sehr an-Schema 11.…”

Regioselective Synthesis of 6‐Vinyl‐3,6‐dihydropyridine‐2(1H)‐ones through Simple Addition of a Vinylmagnesium “Ate” Complex to 2‐Pyridones

“…This would allow additional transformations, and these products seem to be even more valuable building blocks than the compounds shown in Scheme . A simple route to 6‐vinyl‐3,6‐dihydropyridin‐2(1 H )‐ones would also be valuable because the 6‐vinylpiperidine moiety is found in certain naturally occurring compounds, including (±)‐pinidine,19 (+)‐caulophyllumine B,20 (+)‐dienomycin C,21 and galbulimima alkaloids22 (himbeline and himbacine), and also in some synthetic derivatives showing e.g., anticancer15b and antibacterial23 activity. Thus, in this paper we describe the results of the first attempts to activate vinylmagnesium chloride by its conversion into “ate” complexes of type R 3 MgLi by the addition of organolithium reagents, and the application of these “ate” complexes in nucleophilic addition to 2‐pyridones, which in turn enables easy access to 6‐vinyl‐3,6‐dihydropyridin‐2‐ones.…”