Bisindole-type alkaloids voacamine

A characteristic of the genera Callichilia, Conopharyngia, Gabunia, Stemmadenia, Tabernaemontana, and Voacanga of the Apocynaceae family is the presence of bisindole alkaloids of the voacamine type, the prototype of this group being voacamine itself. All these alkaloids are composed of a vobasine-like [vobasine,... 

Some of the most difficult structural problems in the indole alkaloid field are associated with the bisindole alkaloids of the vobtusine type. Since 1955, vobtusine has been isolated on numerous occasions, often in large quantities, from the Apocynaceae species Callichilia, Conopharyngia, Rejoua, and Voacanga A correct molecular formula could only be determined by high-resolution mass spectrometry. In 1966 a partial structure was proposed for the alkaloid and later in the same year a complete structure was put forward. An unambiguous structural proof is, however, still lacking. The difficulty arises from the complete resistance of the alkaloid and its derivatives to cleavage, in contrast, for example, to the dimers of the voacamine and vinblastine types. Non-cleavable dimers occur also in calabash-curare but in these cases chemical correlation with cleavable alkaloids has been possible (see Section 2, p. 209). To date no bisindole alkaloid related to vobtusine has been found which can be split into monomeric units. 

Scheme 25 summarises the molecular ions to be expected from thermal inter-molecular transmethylation of a tertiary N(b>-atom. Such reactions have been investigated with simple model compounds. In the realm of bisindole alkaloids they were first observed with voacamine and vinblastine types. With the help of deuterium labelling it has been shown in the case of voacamine (141) (Section 9, p. 242) that the methyl group of the a-indolylacetic acid methyl ester function of the Iboga component is transferred to the N(b)-atom of the vobasinol component. An a-indolylacetic acid methyl ester is also present in the Vinca bisindole alkaloids (Section 10). It seems probable that the methyl transfer takes place in concert with decarboxylation to give the anion (290). The other methoxycarbonyl group is apparently not involved in methyl transfer. 

In an extensive study of indole alkaloids from Tabernaemontana dichotoma, Perera and co-workers reported the isolation and characterization of eight bisindole alkaloids of the vobasine-coronaridine type (90,93). Of these, the previously known alkaloids tabernamine (173), voacamine (175), and 3 R/S-hydroxyvoacamine (178) were identified from their spectral characteristics and co-TLC with authentic samples (91). UV, IR, and XH NMR data of three of the bisindole alkaloids indicated a close structural relationship to tabernamine (173), and the XH NMR of one of these alkaloids was identical to that of tabernamine, except that the signal at 6 2.62 ppm due to the N-Me group was missing. The MS and IR spectroscopic data... 

A bisindole alkaloid isolated by the French group from Gabunia eglandulosa appears not to be voacamine, and may be new ten others, so far of unspecified structure, have been extracted from Muntafara sessilifolia, and a group of four, from Pandaca caducifolia, belong to a new structural type, but their structures have not yet been elucidated in detail. 

---