D. Catharanthine
Biological Sources It is obtained in the plant of Catharanthus lanceus Pichon (Boj.) (Apocynaceae) (Lanceleaf Periwinkle); and Catharanthus roseus (L.) G. Don (Apocyanaceae) (Periwinkle, Madagascar or Cape Periwinkle, Old Maid). It is also found in Vinca rosea Linn. (Apocynaceae).
Chemical Structure
3, 4-Didehydroibogamine-18-carboxylic acid methyl ester; (C21H24N2O2).
Isolation It may be isolated from Vinca rosea Linn by the method recommended by Gorman et al.**
Characteristic Feature
1. Its crystals obtained from methanol has mp 126-128°C.
2. It has uvmax (ethanol): 226, 284, 292 nm (log ε 4.56, 3.92, 3.88).
3. It has specific optical rotation [α]27D + 29.8° (CHCl3); and dissociation constant pKa′ 6.8.
Uses
1. Its pharmacological action resembles to that of R. serpentina.
2. It also shows beneficial growth inhibition effects in certain human tumors.
3. It is used as a diuretic.
Biosynthesis of Ajmalicine, Vindoline and Catharanthine The various steps involved in the biosynthesis of ajmalicine, vindoline and catharanthine are summarized below:
1. Condensation of secologanin with tryptamine in a Mannich-type reaction gives rise to the tetrahydro-b-carboline system and generates strictosidine.
2. The structural variations involved in converting the Coryanthe type skeleton into the corresponding Aspidosperma and Iboga types are evidently quite complex and are given in the pathway as under.
3. Preakuammicine is obtained from strictosidine via the enol-form of dehydrogeissoschizine.
4. Preakuammicine undergoes intramolecular rearrangement to produce stemmadenine, which subsequently gives rise to a hypothetical intermediate.
5. The hypothetical intermediate may be redrawn which undergoes Diel's-Alder type reaction to produce catharanthine.
6. Dehydrogeissoschizine yields ajmalicine.
7. The hypothetical intermediate gives rise to vindoline via tabersonine.
It is pertinent to mention here that the sequence of alkaloid formation has been proved initially by noting carefully which alkaloids become labelled as a feeding experiment progresses, but more recently it has been confirmed by suitable enzymatic experimental studies.
It is important to mention here that there exists a plethora of structural variants of terpenoid indole alkaloids which may be exemplified with the help of the following specific examples of certain potent alkaloids, namely:
(i) Yohimbine: It is a carboxyclic variant related to ajmalicine and appears to arise from dehydrogeissoschizine by an elaborated mechanism.
(ii) Reserpine: It is a trimethoxybenzoyl ester of yohimbine-like alkaloid. It has an additional-OCH3 moiety at C.-11 of the indole nucleus.
(iii) Rescinnamine: It is a trimethoxycinnamoyl ester of yohimbine-like alkaloid. It also contains an additional methoxyl substituent on the indole-system at C-11.
(iv) Vinblastine: The nucleophilie vindoline, C-5 of the indole nucleous is being activated adequately by the OMe at C-6, besides the N-atom of the indole moiety. The resulting adduct is subsequently reduced in the dihydropyridinium ring by the NADH-dependent 1, 4-addition, giving the substrate for hydroxylation. Its ultimate reduction gives rise to vinblastine.
(v) Vincristine: It is the oxidized product of vinblastine whereby the inherent N-formyl group on the indoline fragment is transformed.
(vi) Strychnine: The loss of one C from a preakuammicine-like structure via hydrolysis/decarboxylation followed by an addition of the additional two C-atoms by means of aldolcondensation with the formyl moiety, complexed as a hemiacetal in the well-known Wieland-Gumlich aldehyde. The ultimate formation of strychnine from its hemiacetal is by virtue of the formation of both ether and amide linkages.
The above mentioned six structural variants of the terpenoid indole alkaloids shall now be discussed individually in the sections that follow.
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* Gorman et al. J. Am. Pharm. Assoc. 48, 256, (1959).
** M. Gorman et al., J. Arn. Pharm. Assoc. Sci. Ed. 48, 256 (1959).
