Cephaeline synthesis

The antidiarrhoeal drug ipecac, which was introduced into Europe from Brazil in 1658, contains the amoebicidal alkaloids emetine (12) and cephaeline. Emetine remained the major remedy for amoebic dysentery and amoebic hepatitis for many years. Cephaeline is less active and more toxic. ( j-2-Dehydroemetine, which is made by synthesis, is equiactive with (—)-emetine and less toxic, but other chemical modification has not yielded better amoebicides. From investigations of synthetic routes to the benzoquinolizine moiety the tranquilizer tetrabenazine (13a) was discovered. The very similar compound benzquinamide (13b) is also a tranquilizer and antiemetic. 

Emetine and cephaeline are both potent inhibitors of protein synthesis, inhibiting at the translocation stage. They display antitumour and antiviral as well as antiamoebic activity, but are too toxic for therapeutic use. In recent studies, O-methylpsychotrine has displayed fairly low effects on protein synthesis, but a quite potent ability to curb viral replication through inhibition of HIV-reverse transcriptase. This may give it potential in the treatment of AIDS. 

Emetine was isolated at the beginning of the nineteenth century, and its chemical structure was determined in the middle of the twentieth century [2].The absolute stereochemistry was clarified [3], and the total synthesis of this alkaloid was achieved [4,5]. On the other hand, cephaeline was isolated early in the twentieth century [6], and its chemical structure, including absolute stereochemistry, was reported at almost the same time as that of emetine [7]. 

Total stereoselective syntheses of emetine and ( )-dihydroprotoemetine and stereoconservative syntheses of deoxytubulosine, cephaeline, and emetine from secologanin have been reported, as has the synthesis of the related alkaloid, desmethylpsychotrine. ... 

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