Total synthesis of pinnamine and anatoxin-a via a common intermediate. A caveat on the anatoxin-a endgame.
[reaction: see text] 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.
Department of Chemistry, Buildings 201 and 207, Technical University of Denmark, Kemitorvet, DK-2800 Kgs. Lyngby, Denmark.
Thomas
T
Hjelmgaard
Inger
I
Søtofte
David
D
Tanner
D000470:Alkaloids / Q000138:chemical synthesis*; D001427:Bacterial Toxins / Q000138:chemical synthesis*; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins / Q000138:chemical synthesis*; D052998:Microcystins; D008956:Models, Chemical; D012694:Serine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism; D014326:Tropanes
D000470:Alkaloids; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D014326:Tropanes; C503219:alpha-trifluoromethylisoserine; D012694:Serine; C509783:anatoxin a