Alkaloid from Vinca rosea Catharanthus

Alkaloid from Vinca rosea (Catharanthus roseus) (Apocynaceae)... 

NSC 49842 Velban Velbe ) is one of the vinca alkaloids from Vinca rosea (Catharanthus roseus) (Apocynaceae). It is a cytotoxic ANTICANCER AGENT used by injection for acute leukaemias, lymphomas and some solid tumours, vinblastine sulfate vinblastine, vincaleucoblastine vinblastine, vincaleukoblastine vinblastine. 

In 1959 a series of bisindole alkaloids were isolated from Vinca rosea L. Catharanthus roseus G. Don). Of signal importance have been vinblastine (169) (= vincaleukoblastine) and vincristine (170) (= leurocristine), both of which show anti-tumour activity (see Section 18, p. 333). Structurally clarified also are leurosidine (= vinrosidine), leurosine, pleurosine, and isoleurosine , while only one half of Catharine is known. 

So far about 72 alkaloids have been isolated from Vinca rosea Liim, genus Catharanthus roseus (Family Apocynaceae). Out of these 24 dimeric alkaloids only six possess antineoplastic activity but specifically two i.e., vincristine, vinblastine, are used clinically in human neoplasms. These are cell-cycle specific agents. 

In 1958, a most curious paper appeared in the Annals of the New York Academy of Science in which even the authors suggested that its appearance was unorthodox. The work was entitled Role of Chance Observations in Chemotherapy Vinca rosea" and needs to be read to be enjoyed. In this work, the authors describe following activity in extracts from Vinca rosea Linn, (now called Catharanthus roseus) through a series of purifications cycles until crystalline material of plant alkaloid is obtained. 

The discovery of medicinal alkaloids from Catharanthus roseus G. Don (Vinca rosea L.) represents one of the most important introductions of plant products into the cancer chemotherapeutic armamentarium. The relatively unique effects and toxicities of these agents have allowed the design of multiagent chemotherapy programs that have demonstrated sufficient effectiveness to achieve cures even of advanced tumors in many instances. This great accomplishment is possible only because of the inclusion of many different drugs, including the binary Vinca alkaloids. 

Vinblastine (4) and vincristine (5) are closely related indole-dihydroindole dimers (bisindole alkaloids), isolated from Catharanthus roseus (L.) G. Don (formerly known as Vinca rosea L.), the Madagascar periwinkle. Both of these anticancer agents, known as vinca alkaloids in the medical literature, are specific binders of tubulin, leading to tubulin depolymerization and cell cycle arrest in the metaphase stage. 

A number of alkaloids with the aspidospermine skeleton occur in the genus Vinca and are dealt with in detail in Chapter 12. They include the very important base vindoline (CIII) which not only occurs as the free base in Vinca rosea (= Lochnera rosea = Catharanthus roseus) but also as part of the dimeric alkaloids vinblastine (vincaleucoblastine) and leurosine, whereas the Aa-formyl analog, CIV, forms part of the dimeric alkaloid leurocristine (5, 72a). These dimeric alkaloids have been used successfully for the treatment of certain forms of cancer in man (5). Vindolinine (CVI) has also been isolated from V. rosea and its dihydro-decarbomethoxy derivative, tuboxenin (CVI-A), which is the parent member of the series, occurs in a Pleiocarpa species (53). ( + )-Vincadif-formine (XCIII, 6, 74) has already been mentioned as the racemic form of (— )-6,7-dihydrotabersonine (Section II, O). It has been found in V. difformis and in Rhazya stricta (51b) where the (+) form also occurs. 

Vinblastine sulfate is the nonproprietary name assigned by the United States Adopted Names Council to the compound originally named vinca-leukoblastine sulfate1 s 3. It is the 1 1 sulfate salt of an alkaloid obtained from the plant Vinca rosea Linn. (Catharanthus roseus G. Don) of the family Apocynaceae, better known as Madagascar periwinkle. Frequently the name is abbreviated to VLB sulfate. It is also identified by the code numbers NSC-49812 and 29060-LE4. The elucidation of the molecular structure, stereochemistry, and absolute configuration of this interesting compound is fully documented in the literature5 7 8. 

Initial methods for the isolation of vinblastine from the periwinkle plants (vinca rosea) had been described (5,7,23-25) and well documented in several texts including the previous profile of vinblastine sulfate (12). Isolation of vinblastine and vincristine from Catharanthus roseus continues to receive attention, and several procedures have been reported (mainly in the patent literature) for the isolation and separation of these alkaloids (24-29). Extracts of Catharanthus roseus have been found to contain N-demethylvinblastine and this can be used to prepare vincristine by formylating the alkaloid mixture before separation and purification (30). 

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