Reserpine applications

In the post-World War II years, synthesis attained a different level of sophistication partly as a result of the confluence of five stimuli (1) the formulation of detailed electronic mechanisms for the fundamental organic reactions, (2) the introduction of conformational analysis of organic structures and transition states based on stereochemical principles, (3) the development of spectroscopic and other physical methods for structural analysis, (4) the use of chromatographic methods of analysis and separation, and (5) the discovery and application of new selective chemical reagents. As a result, the period 1945 to 1960 encompassed the synthesis of such complex molecules as vitamin A (O. Isler, 1949), cortisone (R. Woodward, R. Robinson, 1951), strychnine (R. Woodward, 1954), cedrol (G. Stork, 1955), morphine (M. Gates, 1956), reserpine (R. Woodward, 1956), penicillin V (J. Sheehan, 1957), colchicine (A. Eschenmoser, 1959), and chlorophyll (R. Woodward, 1960) (page 5). ... 

A potentially useful route to reserpine alkaloids has been suggested by the application of the amino-Claisen reaction (Scheme 52) to the indolyl-substituted isoquinuclidine (268). Treatment of (268) with methyl propiolate gave the intermediate zwitterion (269) which rapidly rearranged to (270). This latter compound has all the necessary functionality for further elaboration into the reserpine ring system (B-82MI20700). 

Tetrabenazine, reserpine Deplete amine transmitters, especially dopamine, from nerve endings Reduce chorea severity Huntington s disease other applications, see Chapter 11 Oral Toxicity Hypotension, sedation, depression, diarrhea tetrabenazine somewhat less toxic... 

Hamilton Application Catalog 13. p.8 (1992) resolved from morphine, codeine, thebaine. cocaine, reserpine. and methadone also plant extract [565]. p. 67 HPLC [569.705. p. 215] TLC [656] Sterisomers [757] Stability indicating [755] also [206]... 

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). 

Isobe, M, Fukami, N, Nishikawa, T, Goto, T, Synthesis of chiral cyclohexanes from levoglucosenone and its application to an indole alkaloid reserpine, Heterocydes, 25, 521-532, 1987. 

From the selected applications in Ch. 11.4, it can be concluded that LLE is frequently applied, e.g., in the extraction of risperidone and its 9-hydroxy metabolite [44], of cholesterol-reducing dmgs [51-53], MPH [58], and of LOR and DCL [63, 66, 68]. Next to an one-step LLE followed by evaporation to dryness of the organic layer, two-step LLE procedures with back-extraction to an aqueous phase have been reported as well, e.g., for reserpine [42], atorvastatin [50], and LOR [63]. 

Reserpine and vincaleukoblastine represent the most important plant-derived medicinals introduced into medicine by our generation, and it is instructive to compare their history with those of morphine and quinine. Descriptions of the use of extracts of plants resembling Rauwolfia may be traced back to ancient Hindu ayurvedic writings. They were used in primitive Hindu medicine for a variety of diseases, including snake bite, hypertension, insomnia, and insanity. The early remedies were used for various other purposes, but it seems clear now that our present day application of Rauwolfia alkaloids in treating hypertension and mental disease was foreshadowed in the folk medicine of the Eastern peoples. 

In the history of ethnopharmacology, a most significant event was the isolation and clinical application of the alkaloid reserpine from Rauwolfia spp, a plant that had been used for millennia in the Ayurvedic tradition to treat "madness". Although reserpine had clearly demonstrated antipsychotic efficacy, it was soon replaced by the first synthetic antipsychotic, chlorpromazine, which proved more effective, had fewer side-effects and was relatively inexpensive to manufacture [44]. Exhibit 4 provides overviews for representative studies on natural products with putative anti-psychotic effects. 

Among its first applications was the study of reserpine. Reserpine was isolated in 1952 from Rauwolfia serpentina (Indian snakeroot), which was used for centuries to treat insanity. Reserpine acts by blocking the reuptake NE back into presynaptic vesicles. The same year, Henri Laborit, a surgeon in Paris, administered reserpine to prepare his patients for surgery, because it maden them less anxious. Subsequently, it was widely used to treat patients with severe psychiatry diseases with impressive results. 

Some interesting examples of levoglucosenone s application in the synthesis of natural products and rare carbohydrates have been reported (58-81). Indeed, levoglucosenone has been used in the synthesis of (+)-multistriatin (58,72-73), Prelog-Djerassi lactonic acid (58,59) md (-)-a//o-yohimbane (61) The synthesis of indole alkaloid reserpine (61), and serricomin (58), as well as tetrodotoxin (53,62) were also reported from levoglucosenone or its functionalized derivatives and was reviewed earlier by us (1). 

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