Cook synthesis, -ajmaline

The first enantiospecific total synthesis of (+)-ajmaline [(+)-17] was developed by Cook et al. 161). D-(+)-Tiyptophan methyl ester (126) was converted enantiospecifically, via intermediate 127, to the optically active )-N -benayltetracyclic ketone (-) 107, which was then transformed into the ot,P-unsaturated aldehyde (-)-128. When compound (-)-128 was stirred with 3-bromo-4-hq>tene in die Barbier Grignard process conditions the 1,4-addition products 129a,b... 

Subsequently, Cook disclosed a similar partial synthesis of macrocarpamine (323) by coupling (—)-anhydromacrosalhine-methine (344) with natural pleiocarpamine (342) in anhydrous 0.2 N HCl in THE (Scheme 24) (228-230), providing support for the earlier biogenetic proposal of Hesse (231). The required (—)-anhydromacrosalhine-methine was first partially synthesized from (-l-)-ajmaline (345) to provide an authentic sample (Scheme 25). Degradation to the hemiacetal 346 was carried out following the improved procedure of Sakai (232). This was followed in succession by dehydration, regioselective oxyselenation, selenoxide elimination, and finally 1,4-elimination to yield anhydromacrosalhine-methine (344) in 85% yield. 

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