The Total Synthesis of a Hexacyclic Relay for the Alkaloid Napelline

Abstract

The total synthesis of the racemic compound 12 and its identification with the corresponding optically active derivative prepared from lucidusculine is described.

Dearomative logic in natural product total synthesis

“…Pioneering spectroscopic and degradative structural studies from Pelletier, [138][139][140] Wiesner and Büchi, [141][142][143] and others [144][145][146] revealed the alluring topologies and rich oxidative decor of the aconite alkaloids by the mid 1950s; however, such architectural features characteristic of these remarkable structures have proven so challenging to construct that efficient synthesis of Masamune, [149][150][151][152][153] and Wiesner [154][155][156][157][158][159][160] in the 1960s and 1970s, perhaps only within the last decade has the state-of-the-art of diterpenoid alkaloid synthesis advanced signicantly. This growing renaissance in aconite alkaloid synthesis can be attributed in large part to emerging strategies that place great emphasis on dearomative C-C bond-forming events that construct bridging rings within caged polycyclic frameworks.…”

“…This intermediate could be advanced to veatchine aer several additional steps. 148 Along with their groundbreaking structural studies 141 and early total syntheses of atisine ( 101) 156 and veatchine (102), 155 the substantial synthetic accomplishments of Wiesner's group included their successful pursuit of several members of more challenging diterpenoid alkaloid structural classes, including napelline (104) [157][158][159][160] and the C 19 norditerpenoid alkaloids talatisamine (117) and 13-desoxydelphonine. 162,163 Paramount to Wiesner's approach to napelline (104) was the establishment of a C7-C20 bond during the assembly of the azabicyclo[3.3.1] octane system, which was achieved through Diels-Alder cycloaddition of benzeindene to construct benzonorbornene 118.…”