Hypotensive activities roots

II. HYPOTENSIVE ACTIVITY OF ISOPRENYLATED FLAVONOIDS FROM THE ROOT BARK OF MORUS SPECIES... 

Tacamonine, an indole alkaloid of the Iboga type, isolated from Tabermemontana eglandulosa, the root of which is used to treat snake bites in Zaire, bears structural similarity to the Hunteria alkaloids, eburnamonines, which possess vasodilator and hypotensive activities. Its synthesis in racemic and homochiral form was accomplished by incorporating a classic 6-exo-trig radical cyclization in the key step of the synthesis (Scheme 6)71. The radical precursor 6 was constructed in a 7-step synthesis by starting from racemic or chiral propane-1,3-diol. The radical cyclization of 6 produced the piperidinone in 72% yield as a diastereomeric mixture, which was then transformed into tacamonine. 

Attention should also be drawn to recent publications on the isolation of a new hypotensive factor from the roots of R. serpentina (120). In these publications, the separation of the crude alkaloids from fresh undried R. serpentina roots into four alkaloidal complexes is reported. The first three fractions have been named resajmaline, ajmalexine, and serpajmaline, respectively. The serpajmaline fraction is said to be therapeutically active and also is claimed to contain serpentinine, serpentine, ajmaline, and two unknown substances, one of which is probably reserpiline. This fraction is said also to be free from reserpine and to be much more potent in its hypotensive activity than reserpine, but to lack reserpine s sedative and central nervous depressant action. However, a later pharmacological investigation of an authentic water-soluble serpajmaline fraction (alkaloids present as salts) demonstrated that the type of antihypertensive activity observed closely resembles that of serpentine and serpentinine (121). This conclusion receives support from a chemical study of this fraction in which serpentinine, ajmaline, and tetraphyllicine were obtained in a pure state (121). 

In recent decades, the extracts of leaves, seeds and roots of M. oleifera have been extensively stndied for many potential uses including hypotensive activity (29) and analgesic activity (31, 141). Nitrile, mustard oil glycosides and thiocarbamate glycosides have been isolated and found to be responsible for the hypotensive principles of the leaves (53). Prior to these investigations, there was no instance of the isolation of active hypotensive principles, although the antihypertensive and antispasmodic properties have long been attributed to the species (29,48). 

In 1933, Chopra et al. found that a crystallized alkaloid isolated from the roots of this plant showed hypotensive activity [1]. Subsequently, reserpine, an alkaloid possessing sedative activity, was isolated and characterized in 1952 [2].The chemical structure,including stereochemistry, was determined subsequendy [3,4], and the first total synthesis of reserpine [5] was achieved by Woodward et al. 

The fruit, leaves, and root bark of Lycium chinenese (Solanaceae) are used mainly as a tonic. The methanol extract of the root bark of L. chinense is used as an antipyretic and has shown remarkable hypotensive activity in animals. The active components were isolated and were determined to be alkaloids, named kukoamines A and B [5,6]. Kuko is the Japanese name for L. chinense. These alkaloids are composed of a spermine unit and two molecules of dihydrocaffeic acid, as in the case of the ephedradines described above. The total synthesis of kukoamine A was independently achieved by two groups [7,8]. 

The genus Rauvolfia (about 150 species from the tropics and subtropics) has long been used medicinally. Authenticated reports of the use of R. serpentina as a medicine date back to 1000 b.c. The hypotensive activity of die drug was reported in 1933. As indigenous supplies became depleted in India, the development of R. vomitoria, an African species, and R. tetraphylla, a Central American species, was carried out (Cordell, 1981 Tyler et al., 1981). Because the root of Rauvolfia serpentina contains more than 50 alkaloids, it is not surprising that the crude drug differs in activity from isolated reserpine (39) (Fig. 34.11) (Tyler et al., 1981). The crude drug contains from 0.15% to 0.20% alkaloids. 

Patulin, derived from T. patula, has been shown to reduce capillary permeability is antispasmodic and hypertensive. Hypotensive activity was demonstrated in rats by citric and malic acids isolated from the methanolic extract of T. patula root. Pyridine hydrochloride isolated from the same extract resulted in a hypertensive effect. ... 

About seventy kinds of new phenolic compounds could be isolated from Japanese cultivated mulberry tree (Morus alba, M. bombycis, and M, Ihou) and Chinese crude drug Sang-Bai-Pi (the root bark of Chinese mulberry tree). Most of them are isoprenylated flavonoids. Among them, kuwanon G (1) was the first isolation of the active substance exhibiting the hypotensive effect from the Japanese Morus alba root bark [9]. Furthermore, kuwanon G (1) and its isoprenylated derivative kuwanon H (2) [10] are considered to be formed through an enzymatic Diels-Alder type reaction of a chalcone and a dehydrokuwanon C or its... 

A revised structure for the catecholamide spermidine siderophore obtained from Paracoccus denitrificans has been proposed the new structure contains a centrally located oxazole ring (6).3 The soft coral Sinularia brongersmai contains two spermidine derivatives, i.e. (7) and its 10,11-dehydro-derivative [(lOi )], both of which show cytotoxic activity.4 The hypotensive principle of the root bark of Lycium chinense has been isolated as an amorphous alkaloid called kukoamine A.5 Acid hydrolysis of the alkaloid produced only spermine and dihydrocaffeic acid, which, in association with its n.m.r. spectrum, indicated the structure (8). Another hypotensive principle, ephedradine B (9), has been obtained from Ephedra roots.6... 

The root of Rauwolfia serpentina (snakeroot) contains numerons alkaloids, of which reserpine and rescinnamine are said to be the most active as hypotensive agents (1). 

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