Vincamine from Vinca minor

Further variants on the terpenoid indole alkaloid skeleton (Figure 6.82) are found in ibogaine from Tabemanthe iboga, vincamine from Vinca minor, and ajmaline from Rauwolfia serpentina. Ibogaine is simply a C9 Iboga type alkaloid, but is of interest as an experimental drug to treat heroin addiction. In a number of European countries, vincamine is used clinically as a vasodilator to increase cerebral blood flow in cases of senility, and ajmaline for cardiac arrhythmias. Ajmaline... 

Karabaev, S.S., K.N. Aripov, and T.T. Shakirov. 1972. Isolation of vincamine from Vinca minor. Chem. Nat. Compd. 8(5) 674... 

Vincamine, vinblastine and vincristine are very important clinic alkaloids. They are produced naturally by plants vincamine by Vinca minor, and vinblascine and vincristine by Madagascar periwinkle Catharanthus roseus). The vindoline synthesis pathway starts with strictosidine and, via dehydrogeissoschizine, preakuammicine, stemmadenine and tabersonine, is converted to vindoline and vincristine (Figure 42). Conversion from vindoline to vinblastine is based on the NADH enzyme activity. Vinblastine and vincristine are very similar alkaloids. The difference is that vincristine has CHO connected to N, whereas vinblastine in the same situation has only CO3. This synthetic structural differences influence their activity. Vinblastine is used to treat Hodgkin s disease (a form of lymphoid cancer), while vincristine is used clinically in the treatment of children s leukaemia. Vincristine is more neurotoxic than vinblastine. 

Through a biomimetic approach, tabersonine is also the semisynthetic precursor of vincamine, a Eburna alkaloid isolated from Vinca minor, and is used for cerebral insufficiency in Europe. Tabemanthe iboga has a long history of use as a stimulant in tropical Africa its main active principle is ibogaine, a controlled substance in many countries (Fig. 40). It is being actively investigated in the United States for its potential to induce opium addiction withdrawal. 

Apochlorine was given to rabbits, cats, and dogs intravenously and orally, and it is claimed to have about the same antihypertensive potency as reserpine. Another antihypertensive alkaloid, whose use is apparently favoured in Russia, is vincamine (35) from Vinca minor, which was first described in 1953. ... 

Vincamine (40) is derived from Vinca minor. The in vitro propagation of this plant has been studied (709). Axillary shoot proliferation was best with media containing BAP and NAA. As part of a program for the industrial production of this alkaloid plant cell cultures have been studied as a possible source (710). Petiard and co-workers (711,712) reported the initiation of cell cultures of V. minor based on TLC analysis small amounts of... 

Vincamine, an alkaloid first isolated from Vinca minor has gained wide application in recent years as a specific cerebral vasodilator. Another alkaloid from the same species, (-)-ebur-namonine is marketed with a similar indication. A semisynthetic derivative of vincamine, the (+)-apovincaminic acid ethyl ester is produced under the trade name CAVINTON by the Hungarian Pharmaceutical Company Gedeon Richter. The latter compound has the trade name CALAN in Japan with a substantial share of the market. 

Vincamine constitutes about 25-65 % of indole alkaloids extracted from Vinca minor [24]. 

Vincamine is an alkaloid extracted from the plant Vinca minor. Ethyl apovincaminate is a related synthetic ethyl ester of vincaminic acid. These drugs have spasmolytic effects similar to those of reserpine, but also have metabolic effects, including, in high doses, inhibition of phosphodiesterase. Although increased cerebral blood flow has been reported after the intravenous administration of vincamine, there have been no reliable studies of blood flow after oral medication. Improvement in scores on some psychometric tests have been obtained in some patients with cerebrovascular disease, but no clear-cut practical benefit has been demonstrated. 

Commercial formulations obtained from the alkaloids in Vinca minor may not be free from adverse effects. Ventricular dysrhythmias have been observed, but only after intramuscular or intravenous administration, and they seem to reflect a direct effect on myocardial cells. Hypokalemia and a prolonged QT interval seem to be predisposing factors. Vincamine should therefore be avoided in patients with a prolonged QT interval (SEDA-2, 183) (SEDA-5, 206) (SEDA-5, 207) (SEDA-7, 228). 

Ajmalicine (139a) and 3-isoajmalicine (140a) were both converted to oxindole alkaloids, mitraphylline (167) and isomitraphylline (168) in Mitragyna parvifolia (Roxb.) Korth. (Rubiaceae)(S4). Feeding experiments on Vinca minor Linn. (Apocynaceae) had shown that vincamine (169) is biosynthesized via geissoschizine, stemmadenine, secodine, and tabersonine (85). Apparicine (170), which lacks one carbon atom of the tryptamine side chain, appears to be derived in Aspidosperma pyricollum Miiell. Arg. (Apocynaceae) from stemmadenine (86). 

Almost all the alkaloids isolated from V. minor are derived from the type III moiety 41) belonging to the vincamine, Aspidosperma, and quebrachamine subclasses. In this sense there is more uniformity among the alkaloids of V. minor than the other Vinca species. The alkaloids are also unusual in that amongst the three subclasses are found racemic alkaloids, namely, d(-eburnamine (vincanorine), dZ-A-methylquebrach-amine d -vincadifformine and its dZ-l-methyl derivative (minovine) (see Table II). 

Vincamine (CV) [1089], one of the monoterpenoid-derived indole alkaloids of Vinca minor L., which are quite different in chemical structure from the alkaloids occurring in Vinca rosea, is of interest mainly on account of its ability to produce a sustained h5q)otension - a property also characteristic of the total alkaloids of Vinca rosea [1090-1092]. A number of the studies with vincamine... 

Vincamine is extracted from the leaves of Vinca minor belonging to Apocynaceae family, known as lesser periwinkle native to central and southern Europe. A closely related semisynthetic derivative of vincamine most widely used as medicine is known as ethyl-apovincaminate or vinpocetine [16-19] (Fig. 20.5f). 

---