Olivacine

Olivacine (195) 318-326 XI, XVII affinis, cerifera, echinata, heterophylla, lundii, psychotrifolia... 

Olivacine (195) is also active against L1210 leukemia at 10 mg/kg. 

In 1995, Moreti et al. reported the isolation of janetine (235), 3,4-dihydroolivacine (237), olivacine (238a), and 3-hydroxytetrahydroolivacine (239) from the stem bark of Peschiera huchtienii (H. Winkl.) Markgr. (syn. Tabernaemontana huchtienii H. Winkl.)... 

The UV spectrum (/Imax 222, 239, 269, 290, and 323 nm) of 9-methoxyolivacine (238b) resembled that of olivacine (238a), indicating a similar pyrido[4,3- 7]carbazole framework. The H-NMR spectrum was also similar to that of olivacine, except for... 

Intramolecular Mannich type reaction of the conjugated iminium salt 426 should lead to ellipticine (228) via an intermediate 427. Alternatively, the conjugated iminium salt 426 could hydrolyze to afford the 2-vinylsubstituted indole 428, which, on cyclization through an intermediate 429, would lead to guatambuine (233). This alkaloid, on demethylation and dehydrogenation, should afford olivacine (238a) (375) (Scheme 3.11). 

As an extension of this methodology, Gribble et al. reported a formal total synthesis of olivacine (238a). This synthesis starts from the same keto lactam 1181, used for the synthesis of ellipticine (228), and exploits the lower reactivity of the lactam carbonyl as compared to the carbonyl of the keto lactam. Reaction of the keto lactam 1181 sequentially with methyllithium and superhydiide (LiBHEts) led to 11-demethylellipticine (1191) in 57% yield, along with 30% of ellipticine (228). Finally, using Kutney s procedure (220), ll-demethylellipticine (1191) could be transformed to olivacine (238a) (701) (Scheme 5.195). 

Recently, the same authors reported a different route for the total synthesis of olivacine (238a) and ellipticine (228) starting from 2,4,6-tiimethoxypyiidine (1244) with N-benzylindole-2,3-dicarboxylic anhydride (852) (717,718). Interestingly, this method also uses the same common precursor, N-benzylindole-2,3-dicarboxylic anhydride (852) as shown in Schemes 5.204 and 5.205. Contrary to the earlier route, this sequence involves a Friedel-Crafts acylation of 2,4,6-trimethoxypyridine (1244) with N-benzylindole-2,3-dicarboxylic anhydride (852) (717,718). 

Pyridines and their N- oxides undergo attack by enamines under acylating conditions (Scheme 168), and the results for reactions of N- oxides have been surveyed (B-71MI20500). A modification of this heteroarylation reaction has been employed in the first step of a new synthesis of the antitumor alkaloid olivacine (241 Scheme 169) (81CC44). Electron-withdrawing groups attached at C-4 in the pyridine nucleus appear to facilitate this reaction. 

The reaction of iminium ions with dihydropyridines is a method, suggested from biosynthetic studies, for the formation of carbon-carbon bonds to these six-membered heterocycles. The 1,4-dihydropyridine (8), a presumed intermediate from the reaction of ammonia with glutaraldehyde, reacts with the cyclic iminium ion (159) to give, after oxidation, nicotine (160) (72CC1091). Another example of this reaction has provided a total synthesis of olivacine (163). The 1,2-dihydropyridine ring system in (161), generated from its chromium tricarbonyl complex, was observed to undergo an intramolecular cyclization... 

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