Recent Syntheses and Strategies toward Polycyclic Gelsemium Alkaloids

Abstract

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Experimental and Computational Mechanistic Study of Carbonazidate-Initiated Cascade Reactions

“…All of the expected products were observed in the finished reaction prior to exposure to water without any formation of silanol 15 N-46. After 180 h, the 15 N NMR peak with the greatest area appeared slightly downfield from the starting carbonazidate (Figure 5c). After exposing the reaction mixture to wet air, the peak disappeared, and a new peak that corresponded to silanol 15 N-46 appeared further upfield than the intermediate peak.…”

“…The results of our calculations predict that the former is overall energetically favored over the latter, but we describe below why neither can be ruled out completely simply based on the energiesin other words, both pathways are possible and could be simultaneously operative. To garner experimental support for the mechanism that was based on our calculations, an NMR study was performed using a 15 N-labeled carbonazidate 15 N-41 in CDCl 3 at 75 °C under extremely anhydrous conditions (Figure 5a). The 13 C NMR spectrum showed that intermediate α-diazo oxazolone 15 N-43 was formed after 40 h and then consumed after 180 h (Figure 5b).…”

“…Of these motifs, two important examples are bridged polycycles and propellanes. Carnosol, 11 maoecrystal V, 12 harringtonolide, 13 ialibinone A, 14 and gelsemine 15 are examples of natural products that include a bridged polycyclic motif (Figure 1). Propellanes are tricyclic compounds in which the three rings share a common C−C single bond.…”

Total Synthesis of (−)-14-Hydroxygelsenicine and Six Biogenetically Related Gelsemium Alkaloids

“…Scheme 3. Asymmetric Total Synthesis of (−)-14-Acetoxygelsedilam (3), (−)-14-Hydroxygelsenicine (7), and (−)-Gelsemolenine A(4) …”

“…Much effort has been made to accomplish the total synthesis of gelsedine-type alkaloids. 4 The first total synthesis of ent-gelsedine was completed in 21 steps by Hiemstra and co-workers in 1999, which features the construction of a 7-azabicyclo[4.2.1]nonane system by intramolecular addition of an allene to an N-acyliminium intermediate followed by the construction of an oxindole moiety by the palladium-catalyzed Heck reaction. 5 Later, Fukuyama and co-workers accomplished a spectacular total synthesis of gelsemoxonine, 6a spirocyclopropane-isoxazolidine to furnish an azetidine moiety.…”