Quirante Josefina, Paloma Laura, Diaba Faïza, Vila Xavier, Bonjoch Josep
Laboratori de Química Orgànica, Facultat de Farmàcia, Institut de Biomedicina, Universitat de Barcelona, Av. Joan XXIII s/n, 08028-Barcelona, Spain.
J Org Chem. 2008 Jan 18;73(2):768-71. doi: 10.1021/jo702340w. Epub 2007 Dec 21.
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.
从4-(氨基甲基)苯甲醚衍生物开始，通过10步反应实现了马达加明生物碱三环核心的合成。进行Birch还原反应并用氰基乙酸进行酰化，随后进行分子内迈克尔反应，得到多官能化的顺式全氢异喹啉。酰胺、腈和酮基团的非对映选择性烯丙基化和还原反应生成双环醇，该双环醇通过 nosyl 衍生物进行氨基环化反应生成二氮杂三环。
