Akuammiline-vincorine alkaloids

Minfiensine (99) [43] exemplifies a variety of indole alkaloids containing the novel l,2,3,4-tetrahydro-9a,4a-(iminoethano)-9/7-carbazole ring skeleton. These include minfiensine (99), vincorine (100) [44], corymine (101) [45], and echitamine (102) [46] (Fig. 4). They exhibit a number of impressive biological activities, including significant anticancer activity [47]. Since the first characterization of the first akuammiline alkaloid member echitamine (102), more than 80 years ago, only a few successful syntheses of this challenging tetracyclic system have been reported. 

An additional six steps consisting of deprotections, oxidations, and meth-ylations completed the first total synthesis of an akuammiline alkaloid, ( )-vincorine (18). This racemic synthesis took a total of 31 steps and proceeded with a 1% overall yield. 

This reaction is proposed to proceed via iminium ion 148, which is formed by conjugate addition of C3 of the indole moiety to the actiwited acrylate. Intramolecular attack by the amide nitrogen on the iminium carbon then leads to cychzation to complete the transformation. No further efforts toward the akuammiline alkaloids have, as yet, been reported, but the authors propose that this method could be employed to construct vincorine (18). 

R = aryl, alkyl, R = aryl, R = H, OMe, R" = H, alkyl, allyl, akuammiline alkaloid vincorine... 

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