Methyl reserpate

The 3,4,5-trimethoxycinnamic ester of methyl reserpate is also present in Rauwolfia plants and obtainable in purified form therefrom by extraction as described in U.S, Patents 2,974,144 and 2,876,228. 

C 4HhjNO 87849-03-4) see Acrivastine Triprolidine (l-methyl-2-pyrrolyl)acetonitrile (C7H, N2 24437-41-0) see Tolmetin methyl reserpate... 

The isolation of methyl reserpate (121) from Rauwolfia vomitoria Afz. (42) and R. obscura K. Schum. (88) and of methyl deserpidate (122) from Rauwolfia obscura K.Schum. (89) has been reported by Court and coworkers. It should be mentioned that these compounds may not be primary products but only artifacts formed by hydrolysis of reserpine (109) and deserpidine (110), respectively. 

The 400-MHz NMR chemical shifts and most of the main coupling constants of reserpine (109), deserpidine (110), rescinnamine (111), and methyl reserpate (121) have been reported by Lounasmaa et al. (400). 

The oxidation probably involves a mercurated complex through the electron pair on nitrogen followed by a concerted removal of a proton from the a-carbon and then cleavage of the mercury-nitrogen bond. The suggestion that a trans elimination occurs is reinforced by the evidence that yohimbine can be hydrogenated by mercuric acetate, whereas reserpine methyl reserpate, deserpine, or pseudoyohimbine does not react [122]. 

Reserpine is metabolised by the liver (3 2-3U) with more than 90% excreted as metabolites(33). The major urinary metabolites are methyl reserpate and 3,5-trimethoxy-benzoic acid. Other metabolites are shown in Scheme 3 (35). 

Common Name 3,4,5-Trimethoxycinnamoyl methyl reserpate Structural Formula ... 

Trimethoxycinnamic acid Methyl reserpate Thionyl chloride Rauwolfia plants... 

In contrast to the oxidative reactions discussed above, the only reported biotransformations of reserpine (21) and rescinnamine (23) (42-44) appear to involve hydrolytic processes. Reserpine is readily metabolized by liver homogenates from the mouse (43), rat, guinea pig, dog, and cat (44) to yield methyl reserpate (22) and 3,4,5-trimethoxybenzoic acid in yields of up to 70% (43). The use of reserpine labeled with tritium in the 2 and 6 positions of the trimethoxybenzoate residue indicated that no significant metabolism of reserpine by another route occurred before hydrolysis, reserpine and 3,4,5-trimethoxybenzoic acid being the only detectable radioactive components of the incubation mixture at the conclusion of the reaction (44). An... 

With the exception of raujemidine, the structures of the compounds in Table IV have been obtained by a combination of partial degradation, parallelism of properties with reserpine or deserpidine, and partial synthesis. Thus, the structure of methyl raunescate rests entirely upon those reactions which were authenticated in the case of methyl reserpate and deserpidate. Methyl pseudoreserpate was partially synthesized from reserpine (132), which established its structure except for the attachment of the acyl residue. Apart from the biological activity evinced by the... 

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). 

A number of stereoisomers of methyl reserpate have been prepared by chemical manipulations. They have all retained the cis DE ring configuration, and so far no diastereoisomer of methyl reserpate with the equivalent tfraws-fused system has been prepared synthetically. 

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. 

The stereoisomeric methyl reserpates (see Table V) were prepared in the following ways. 

At an early date it was already recognized that the ketone (IX) derived from an oxidation of the C-18 carbinol function of methyl reserpate could be of considerable utility for further transformation of the reserpine pentacyclic ring system, but early attempts at the preparation of the desired compound by conventional oxidation, e.g., by Oppenauer s method, AAchlorosuceinimide, sodium dichromate, or chromic oxide in pyridine, were unsuccessful with both methyl reserpate and methyl 18-epireserpate. The ketone was finally obtained by heating methyl reserpate p-bromobenzene sulfonate with dimethyl sulfoxide in the presence of triethylamine (162), a method successfully used for simpler compounds (163). Subsequently, it was found that this oxidation could also be realized with other benzene sulfonate esters of methyl reserpate and 18-epireserpate. That the stereochemistry of the molecule was unaffected was proved by sodium borohydride reduction of the ketone, which gave equal amounts of methyl reserpate and its 18-epimer. This and other simple reactions of the ketone are sketched in Chart III, and additional observations will be given. 

---