Synthesis of diazatricyclic core of Madangamines from cis-perhydroisoquinolines.
Synthesis of the tricyclic core of madangamine alkaloids has been achieved in a 10-step sequence starting from a 4-(aminomethyl)anisole derivative. A Birch reduction and acylation with cyanoacetic acid followed by an intramolecular Michael process renders a polyfunctionalized cis-perhydroisoquinoline. A diastereoselective allylation and reduction of amide, nitrile, and ketone groups leads to a bicyclic alcohol, which undergoes aminocyclization through the nosyl derivative to the diazatricyclic ring.
Quirante
Josefina
J
Laboratori de Química Orgànica, Facultat de Farmàcia, Institut de Biomedicina, Universitat de Barcelona, Av. Joan XXIII s/n, 08028-Barcelona, Spain.
Paloma
Laura
L
Diaba
Faïza
F
Vila
Xavier
X
Bonjoch
Josep
J
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry; D007546:Isoquinolines / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000470:Alkaloids; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines