Reserpine-type alkaloids

Waldmann used (R) and (5>aminoacid methyl esters and chiral amines as chiral auxiliaries in analogous aza-Diels-Alder reactions with cyclodienes.111 The diastereoselectivity of these reactions ranged from moderate to excellent and the open-chain dienes reacted similarly. Recently, the aza-Diels-Alder reaction was used by Waldmann in the asymmetric synthesis of highly functionalized tetracyclic indole derivatives (Eq. 12.45), which is useful for the synthesis of yohimbine- and reserpine-type alkaloids.112... 

The previously known reserpine-type alkaloids (3) are shown below. They are reserpine (109), deserpidine (110), rescinnamine (111), veneserpine (112), pseudoreserpine (113), raunescine (114), rescidine (115), raugustine (116), and isoraunescine (117). It should be mentioned that all reserpine-type alkaloids are trisubstituted at ring E and that the substituents at C-16, C-17, and C-18 are all in equatorial positions on the epiallo yohimbane ring system existing predominantly... 

The isolation of a new reserpine-type alkaloid from Rauwolfia vomitoria Afz. named neonorreserpine has recently been reported however, the stereochemistry of its substituents attached to ring E has not yet been established (86). 

The arbitrary classification of Rauwolfia alkaloids (91) is simplified here, and it is slightly different from a recent arrangement (92). The Rauwolfia alkaloids can all be regarded as yohimbinoid derivatives as shown in Chart I, viz. the yohimbines (all yohimbine isomers) 18-hydroxyyohimbines (reserpine-type alkaloids) ring E heterocycles and their anhydronium analogs (ajmalicine, serpentine) ajmaline-type (which includes sarpagine) and compounds of unknown constitution. 

The hydrogen abstraction, in this instance, presumably occurs at the P-carbon of the enone (139). The resultant biradical ring closes to afford the observed products. The ic-ic excited triplet state is involved in the conversion of the enone (141) into the spiroketone (142). The reaction again involves hydrogen abstraction by the ft-carbon followed by cyclization within the biradical. Photocyclization of enamides such as (143) has led to a new synthetic approach to the yohimbine an[Pg.201]

W. S. Johnson, M. Neeman, S. P. Birkeland, and N. A. Fedoruk. Am. Soc., 84. 989 (1962) Osmium tetroxlde-Barium chlorate. For the hydroxylation of (1), an intermediate in the synthesis of reserpine-type alkaloids, a Czech group found that use of barium chlorate with osmium tetroxide, taken in catalytic amount rather than in equivalent amount, gave improved yields of the diol (2). The starting material (1) was shaken... 

The relative stereochemistry between the C(3) and C(18) stereocentres of the dodecahydroindolo[2,3-fl]benzo[ ]quinolizine skeleton of reserpine-type alkaloids has been reported from a highly torquoselective thermal triene 6k electrocyclization (Scheme 30)." ... 

The stem bark of P. yohimbe (= P. johimbe Corynanthe yohimbe), "yohimbe as it is known in Cameroon, Gabon and Congo is used traditionally as an aphrodisiac and stimulant to prevent sleep (41). The bark contains 1-6% of indole alkaloids, most of which are yohimbane-type alkaloids, the main one being yohimbine [7], which is structurally related to reserpine [8] (89). Yohimbine is a selective inhibitor of a-2- adrenergic receptors and, while at low dose it has hypertensive activity, at high dose it is hypotensive (vasodilation of peripheral vessels). It is the vasodilation of peripheral vessels, and especially vasodilation of the corpus cavemosum, which is the cause of the reputation of yohimbine as an aphrodisiac (90). Tests have shown, indeed, that increased... 

As a route to the c/5-hydroisoquinoline moiety of reserpine-type indole alkaloids, further additions to dihydropyridines have been investigated. Following successful [4 -I- 2] cycloaddition to acrolein, subsequent elaboration permitted selective generation of the required stereochemistry by Cope rearrangement (Scheme 4). Investigations aimed at the synthesis of Erythrina alkaloids have... 

Some indolo[2..w/]c iiinolixidines undergo easy acid-catalyzed epimerization <1998H(50)243>. For instance, the alkaloid reserpine equilibrates to a mixture of starting material and its 3-epimer, isoreserpine, under acid or basic catalysis (Equation 6). A controlled epimerization of this type has been employed as the key step in a total synthesis of ( )-tacamonine <1998T157>. 

In the sympathetic nervous system there is the possibility to reduce the release of noradrenaline. The alkaloid reserpine is known to interfere with the ability of the postganglionic sympathetic nerves to store noradrenaline. This results in a reduction of the sympathetic tone which is a useful measure in the treatment of essential hypertension. These type of drugs are classified as antisympathotonics. 

Dissimilarity (opposite effect) due to bulky side groups hindering the action ot compounds containing the ethyiamine moiety were also found. Again the data base lacked a descriptor indicating the medical use property sympatholytic. Examples ot such compounds would be tranquilizers such as the reserpine alkaloids. An effective search strategy for compounds ot this type has not been developed and consequently the space for them in Table IV cannot yet be filled in. 

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). 

Considering that oxoisoaporphine (7/f-dibenzo[rfe,/ ]quinolin-7-one ) have obtained the interest for its versatility in the synthesis of new derivatives in diverse medical action fields as its use in such parasitic diseases like Malaria [25] or Leishmania [26], the study of behavioral diseases as depression through compoimds that inhibit the human monoamino oxidase A (hMAO-A) or to reverse the depressed state in reserpinized animal testing, has been the first impulse to compile references of this type of alkaloid in the therapeutic scope under the observation of the neoplastic and psychiatric diseases. 

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