Reserpic acid

Reserpic acid (120) has been isolated from Rauwolfia vomitoria Afz. (87). The authors stated that the compound was not a secondary product of the isolation, however, the question is still open. 

Immediate sodium borohydride (NaBfLt) reduction gave lactam 44. Bischler-Napieralski cyclization of 44 followed by NaBfLt reduction yielded ( )-methyl-0-acetyl-isoreserpate (45). The correct stereochemistry at C-3 was obtained by first lactonizing compound 45 epimerization with pivalic acid then resulted in ( )-reserpic acid lactone (47). Treatment with base followed by acylation with TMBCI yielded racemic reserpine. The stereochemical considerations involved in the epimerization reaction will be discussed later. 

Fig. (13). Stereoformulas of isoreserpic acid lactone (46) and reserpic acid lactone (47).

Chaplin L, Cohen AH, Huettl P, Kennedy M, Njus D, Temperley SJ (1985) Reserpic acid as an inhibitor of norepinephrine transport into chromaffin vesicle ghosts. J Biol Chem 260 10981-10985. 

A brief, selective review of epimerizations in the isoquinoline and indole alkaloid series inevitably gives prominence to epimerizations at C-3 of tetrahydro-/3 -carbo-line derivatives, in particular of reserpine and reserpic acid lactone the epimerizations involved in Brown s synthesis33/ of Afa-methyl-tetrahydroalstonine and 3/3-H,20/3 -H-lVa-methyldihydrogeissoschizine, from ATb-benzyl-lVa-methylvincoside, are also discussed.69... 

Much of the chemistry of reserpine and its congeners becomes clear and compelling if the conformational mobility of the CDE rings of its 3-epialloyohimbane nucleus is remembered (134). It was the gradual realization of this property and how to take advantage of it that led to the very elegant experiments which established the complete relative stereochemistry of the reserpine molecule (135, 136). Not unexpectedly, it is found that reserpine under normal conditions prefers the cis-trans-cis CDE conformation (137, 138), but this does not prevent it from assuming the trans-trans-cis shape to make possible the formation of reserpic acid lactone (125) and the quaternary salt III (136). 

The absolute chemistry of reserpine has been derived directly (135), by making use of Klyne s extension of the Hudson lactone rule (147) as applied to reserpic acid and its lactone, as well as by the application of Prelog s asymmetric synthesis (148) to methyl reserpate (149). These results are in agreement with the conclusions obtained by more indirect but no less accurate means (91). 

Contrary to earlier assumptions that activity was present only in reserpic acid diesters, it was found that methyl 18-epireserpate itself possessed distinct sedative, but not antihypertensive, activity (159). Methyl reserpate and methyl isoreserpate were completely inactive, and the three other methyl reserpates have not been tested. 

Acyl Derivatives of Reserpic Acid and Methyl Reserpate... 

Reocorin, 920 Reorganin, 645 Reoxyl, 657 Repeltin, 1046 Repocal, 863 Repoise, 415 Rescinnamine, 957 Resercen, 958 Reserfia, 958 Reserpanca, 958 Reserpic acid, 958 Reserpine, 958... 

The closely related alkaloids rescinnamine (XLV, R = 3,4,5-trimethoxy-cinnamyl Fig. 3) [982, 1030-1043] and deserpidine (11-desmethoxyreserpine) [982,1036-1039,1042,1044-1047] exhibit similar, though less potent, sedative and hypotensive properties to reserpine and they have seen clinical apphcation. In the synthetic compound methoserpidine the hypotensive properties are free from accompan5dng sedation provided only moderate doses are given [1048 to 1050], while the reserpic acid di-ester syrosingopine, exerts a mild h3 otensive effect with practically no accompanying sedation [1050-1057]. 

Malik A, Afza N 1983 Reserpic acid, gallic acid, and flavonoids from Rauvolfia vomitoria. J Nat Prod 46 939... 

This alkaloid is similar to reserpine except that the reserpic acid moiety of the molecule is esterified with trimethoxycinnamic acid rather than with trimethoxybenzoic acid. A non-aqueous titration similar to that given above is applicable (1 ml 0 05N 0-03174 g), or the colorimetric nitrite procedure may be applied. If the sample is thought to be contaminated with some of the other alkaloids of rauwolfia (less weakly basic), an extraction procedure can be applied followed by colour development as in the recommended method above. An aliquot of a suitable extract is diluted with 0-5N sulphuric acid and the aqueous ethanol is then extracted with trichloroethane which is discarded. The rescinnamine is then separated from other alkaloids by extracting the acid solution with chloroform and a suitable aliquot of the chloroform solution, containing 100 to 300 fxg of rescinnamine is evaporated and used for the colour development stage. The rescinnamine content is obtained from a standard curve prepared using a solution of rescinnamine in 95 per cent ethanol. 

Similarly to reserpic acid lactone, in rauniticine, the epiallo system, specifically the trans-trans-cis conformer, is favoured under acid equilibrating conditions because it releases the molecule from the steric crowding of the axial 19j3-methyl upon the lone pair nitrogen orbital and the 14j3-proton in both the alio form and the cis-trans-cis epiallo conformer. 

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