Total synthesis of (+/-)-didehydrostemofoline (asparagamine A) and (+/-)-isodidehydrostemofoline.
The first total syntheses of (+/-)-didehydrostemofoline (1) and (+/-)-isodidehydrostemofoline (3) are reported. The synthesis begins with the Diels-Alder reaction of readily available pyrrole 9 and ethyl (E)-3-nitroacrylate, the latter serving as a regioinverted equivalent of ketene. After hydrogenation to prevent retro-Diels-Alder reaction, the major cycloadduct is transformed to 7-azabicyclo[2.2.1]heptanol 14. Aza-Cope-Mannich reaction of the formaldiminium derivative of 14 delivers 1-azatricyclo[5.3.0.04.10]decane 15, which in 15 additional steps is converted to 1 and 3.
Brüggemann
Markus
M
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, CA 92697-2025, USA.
McDonald
Andrew I
AI
Overman
Larry E
LE
Rosen
Mark D
MD
Schwink
Lothar
L
Scott
Jeremy P
JP
D000470:Alkaloids / Q000138:chemical synthesis*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D041901:Stemonaceae / Q000737:chemistry*; D013237:Stereoisomerism
D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; C481859:didehydrostemofoline; C481860:isodidehydrostemofoline