| Aphanorphine was isolated by Yuzuru Shimizu et al. from blue-green alga, Aphanizomenon flos-aquae in the year of 1988, which was an alkaloid with a benzazepine skeleton. And the Aphanizomenon flos-aquae was reported to contain neurotoxins. Although to date no biological activity of Aphanorphine has been reported, Aphanorphine shares common structural features with other bioactive (analgesic) benzomorphan alkaloids, such as morphine, pentazocine, and eptazocine.We are supposed to construct the five-membered nitrogen-containing heterocycle via Iron (Ⅲ)-catalyzed aza-Cope-Mannich reaction, a concise approach to the synthesis of Aphanorphine. At first, the 2-(4-methoxyphenyl)-acetaldehyde reacts with alkynol to give the rearrangement product. Then the aldehyde is reduced to double bond, which will convert into 6,6,5-tricyclic skeleton by Friedel-Crafts reaction. Subsequently, remove out the protected group of amine and then methylatation of amine and demethylation of phenolic hydroxyl, the Aphanorphine is obtained in 6 steps.The research idea of Ag (Ⅰ)-catalyzed ring-contractive rearrangement of 6-diazocyclohexenones is proposed and directed by Dr. Liang Zhao, who has graduated from our group. And my main task is to assist him to complete this work. I will present a review of reactions of diazocompounds in this thesis, and clarify my participation in this work.We performed our research on the Ag (Ⅰ)-catalyzed ring-contractive rearrangement with the 6-diazocyclohexenones as substrates. The AgOTf-catalyzed reaction proceeds through metal-carbenoid formation followed by migration of the C4-C5 bond. The produced carbocation delivers 5-alkylidene-2-cyclopentenone which is a basic skeleton of many pharmaceuticals, here we completed the synthesis of it through an efficient and versatile protocol, which should be applied into the synthesis of natural products. |
