Total Synthesis of Pinnamine and Anatoxin-a via a Common Intermediate. A Caveat on the Anatoxin-a Endgame

This paper describes the total synthesis of the naturally occurring alkaloids pinnamine (1) and
anatoxin-a (2) from a common enantiomerically pure intermediate (7) easily available from
pyroglutamic acid. The synthesis of enantiopure pinnamine proceeded in 10 steps and 4.8% overall
yield, and the route was flexible enough to allow stereocontrolled access to a non-natural congener
(5-epi-pinnamine) of the natural product. Intramolecular reaction of an N-acyl iminium ion was a
key step in the synthesis of both pinnamine and anatoxin-a. However, in stark contrast to literature
precedent, complete racemization was observed during the reaction of the N-acyliminium ion leading
to the latter alkaloid.