Cinchona succirubra alkaloids

Quinine Quinine, molecular formula C20H24N2O2, is a white crystalline quinoline alkaloid, isolated from Cinchona hark Cinchona succirubra), and is well known as an antimalarial drug. Quinine is extremely bitter, and also possesses antipyretic, analgesic and anti-inflammatory properties. While quinine is stiU the drug of choice for the treatment of Falciparum malaria, it can be also used to treat nocturnal leg cramps and arthritis. Quinine is an extremely basic compound, and is available in its salt forms, e.g. sulphate, hydrochloride and gluconate. 

Leaves of Cinchona succirubra Pav. from a trial plantation in the north of Thailand have been reported to contain the typical bases of quinoline alkaloids (cinchonine, cinchonidine, quinidine, quinine, di-hydroquinidine, and dihydroquinine) together with the indole bases quina-mine and 3-epiquinamine (97,98). 10-Methoxycinchonamine (92) has also been isolated from this plant for the first time. Except for the inclusion of alkaloid 92, the alkaloid pattern in C. succirubra is the same as that in the cross-species C. succirubra x C. ledgeriana from Guatemala. 

Alkaloids are one of the most important classes of natural product providing drugs for humans since ancient times. Most alkaloids are well known because of their toxicity or use as psychodelic drugs (e.g. cocaine, morphine or the semisynthetic LSD), but many alkaloids have had a deep impact on the treatment of parasitic infections. The outstanding example is quinine (1) from Cinchona succirubra (Rubiaceae) used for the treatment of malaria for more than three centuries. 

Quinine isolated from Cinchona succirubra represents the oldest example of quinoline alkaloids antiparasitic effects, particularly antiplasmodial activity it has been used to treat malaria for more than three centuries. Other quinoline alkaloids such as 2- -propylquinoline, chimanine B, 2-n-pentylquinoline, and 4-methoxy-2-phenylquinoline have been also shown to be effective against strains of parasites causing cutaneous leishmaniasis [189,190] (Fig. 25). 

Cinchona succirubra (Rubiaceae) is a tall tree that grows wild in the Andes of Peru and Brazil. It is cultivated in Java and Sumatra. The bark contains 5%-8% total alkaloids. The major alkaloid, quinine, has been used as an antimalarial agent. Cinchonidine, cinchonine, and quinidine have also been obtained. 

Catechins are particularly good nucleophiles, so it is not surprising to find these compounds substituted at the A-ring with other natural products. The bark of Quercus stenophylla contains ellagitannins that are linked by carbon carbon bonds to the C-6 or C-8 of catechin (277). Kopsirachin (25), from Kopsia dasyrachis, is a most interesting example of this type of catechin derivative in which both the C-6 and C-8 positions are substituted by the alkaloid skytanthine (160). Other examples of this type of compound are the C-6, C-8, and C-6 -l- C-8 cinnamate derivatives of catechin isolated from Cinchona succirubra (273, 279). It can be predicted that many more examples of this type of catechin derivative will be found in the future. 

Cinchona rubra, red cinchona, is the bark of C. Succirubra or of its hybrids, containing not less than 5% of cinchona alkaloids. From it is prepared the compound tincture of cinchona. 

Because of the value and the widespread use of Cinchona alkaloids, many attempts to produce alkaloids in plant tissue cultures and cell cultures from this group of plants have been made (Verpoorte et al., 1991). Trees require about 10 years before they can be harvested. Cell cultures of Cinchona ledg-eriana and C. succirubra produce largely cinchonine (67) and cinchonidine (68), although small quantities of quinine and quinidine were produced. Only small amounts of total alkaloids were produced (Ellis, 1988). 

Investigation of the leaves of various Cinchona tree species showed that they differ remarkably in the alkaloid composition. For example, C. ledgeriana contains mainly indole type alkaloids (e.g., cinchophyllamines 10, quinamine 11a, and 3-epiquinamine 11c) [76-79], in contrast to the samples of C. succirubra... 

Cinchona are produced predominantly in the aerial part of the plant, since the scions of C. ledgeriana are rich in alkaloids regardless of the root on which they are grafted. In this species, the level of alkaloids and the qualitative composition invariably remain the same, whether the plants are grown on their own roots or are grafted on roots of C. succirubra (Moens, 1882). Moerloose (1954) found that the leaves and bark produce radioactive alkaloids when exposed to C02 the rate of growth was related to alkaloid production. 

The League of Nations Malaria Commission defined totaquine as a preparation standardised to contain 70 per cent of crystallisable alkaliods, of which quinine should constitute not less than 15 per cent, with not more than 20 per cent amorphous alkaloids, 5 per cent of mineral matter and 5 per cent of moisture. It was introduced as a cheap substitute for quinine and no particular cinchona species is prescribed as a source provided it has the required composition, but the composition permits it to be made by extraction of the total alkaloids of C. succirubra or C. rohusta. 

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