Vinca - Vincamine

Among the examples of monoindole bases being discussed, vincamine (109) is the principal alkaloid of Vinca minorC. and has received some notoriety because it apparently causes some improvement in the abiUties of sufferers of cerebral arteriosclerosis (78). It is beheved that this is the result of increasing cerebral blood flow with the accompanying increase in oxygenation of tissue as a result of its action as a vasodilator. 

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. 

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... 

The study of the chromatographic behavior of natural indole alkaloids on cyclodextrin polymers was different, and unexpectedly high retentions were observed in mildly acidic buffer solutions at room temperature, which permitted their separation by inclusion chromatography (25) (Table IV). Figure 7 shows the separation of two Vinca-alkaloids of very similar structure, the (+)-vincamine and (+)-apovincamine. 

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. 

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). 

DNP dinitrophenyl CBZ carbobenzoxy OBzl benzylesters /3NA naphthyl amide TCP tetrachlorofluorescein amaryllis alkaloids crinine, powelline, and crinamidine vinca alkaloids vincamine and vincine structural isomers 2- and 6-nitro-3-acetamido-4-chlorobenzoic acid stereoisomers 4-methoxymethyl-l-methyl-cyclohexane carboxylic acid fish oil mixture of docosahexaenoic acid and eicosapentaenoic acid NDGA nordihydroguaiaretic acid. 

Chrom Q column by Gazdag et al.. Derivatization (silylation with N,0-bis(trimethylsilyl) trifluoroacetamide) was needed for those alkaloids containing free hydroxy groups and/or a carboxylic acid group (vincaminic and apovincaminic acids). In Table 17.6 the retention times and elution temperatures of the vinca alkaloids investigated - as such and as derivatives -are given. 

Tabersonine.(-) and (+)-vinca-difformine.vincamine.apo- and ethylapo-vincamine,quebracha-rni ne, N-methy 1 quebrachami ne, (-)-vincadine... 

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. ... 

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). 

Epivincamine (mp 181°-185° Mp—36° in CHCI3) has been found among the alkaloids of Vinca minor L. and it was very similar in its IR- and UV-spectra to vincamine 23). The mass spectrum with peaks at M, M-15, M-18, M-29, M-47, M-59, M-70, and the intense peak at M-102 were nearly identical with those of vincamine differing somewhat in the intensity of some peaks and mainly in the peak at m/e 266 which in vincamine is found at m/e 267. Reduction of the alkaloid gave 16-epivincaminol which after oxidation with periodic acid furnished (— )-eburnamonine. Another proof for the C-16 isomerism was obtained... 

Vincamine Vinca species 29.50 Vinca minor SC 3.3 g/liter... 

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... 

Crespi et al. (715) patented the production of vincamine and epivin-camine by means of cell cultures of V. minor. Yields of 3.3 and 0.9 g/liter, respectively, were claimed for the two alkaloids. Two other patents have been reported concerning the production of Vinca alkaloids (Table XLIII). 

The molecular skeleton of infractopicrin resembles that of vincamine, a representative alkaloid which lowers blood pressure, isolated from plants of the genus Catharanthus (Vinca). There is, however, no evidence of a biogenetic relationship of these alkaloids, and the absence of an angular ethyl group in infractopicrin and in the accompanying metabolites suggests rather different biosynthetic pathways in both cases (177). Studies on the canthin-6-one alkaloids of various natural origins were recently reviewed by Ohmoto and Koike in Volume 36 of this treatise (179). 

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

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