Reserpine structure

Registiy of Mass Spectral Data, 412 Replication (DNA). 1106-1107 direction of, 1107 error rate during. 1107 lagging strand in, 1107 leading strand in, 1107 Okazaki fragments in, 1107 replication fork in, 1107 Replication fork (DNA), 1107 Reserpine, structure of, 65 Residue (protein), 1027 Resist, photolithography and, 505-506... 

Common Name l-[2-(Diethylamino)ethyl]reserpine Structural Formula ... 

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). ... 

Woodward then moved across town in Cambridge to devote a year of postgraduate study at Harvard University. At the end of that year, he accepted an appointment to the Harvard chemistry faculty, a post he held for most of the rest of his life. One of his great interests at Harvard was the synthesis of large, complex molecules, the first of which was quinine in 1944. He followed that work with the elucidation of other molecular structures and the development of synthetic methods for each. Included among these molecules were penicillin (1945), patulin (1948), cholesterol and cortisone (1951), oxytetracycline (1952), strychnine (1954), lysergic acid (1954), reserpine (1956), chlorophyll (1960), colchicine (1963), cephalosporin C (1965), and vitamin (1971). 

The determination of 17-ketosteroids is most often determined in the clinical laboratory by the Zimmerman reaction, in which the ether-extracted material is allowed to react with m-nitroaniline to yield a colored product. Thus, any compound with the 17-keto basic structure such as reserpine, morphine, ascorbic acid, or their metabolites will interfere. The Porter-Silber reaction used in the determination of 17,21-dihydroxysteroids is also not specific, and the reaction requires a di-hydroxyacetone side chain. Paraldehyde, chloral hydrate, meprobromate, and potassium iodide have been found to interfere, and patients should be maintained free of these drugs for 24-48 hours before the urine collection (Bll). 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

The Rauwolfla alkaloid reserpine was originally used as a neuroleptic/antipsychotic agent. It was then discovered to be an effective antihypertensive agent. Reserpine causes depletion of the noradrenaline stores in peripheral postganglionic sympathetic neurons. In addition it causes depletion of noradrenalin in central nervous structures involved in the regulation of blood pressure. 

The spectrum of activity of a-methyldopa (Aldomet) lies between those of the more potent agents, such as guanethidine, and the milder antihypertensives, such as reserpine. a-Methyldopa is a structural analogue of di-hydroxyphenylalanine (dopa) and differs from dopa only by the presence of a methyl group on the a-carbon of the side chain. 

Dihydropyridines have also been starting points for stereospecific syntheses of hydro-phenanthridines and isoquinolines. Interest exists in these compounds because of the occurrence of this structural feature in alkaloids. For example, isoquinuclidine (263), derived from JV-alkoxycarbonyl-l,2-dihydropyridine, undergoes a Cope rearrangement to give the isoquinoline derivative (264) (80JA6157). Further chemical transformations of (264) provided a formal total synthesis of reserpine (Scheme 50). 

It became known in the same year (1954) that the substance reserpine, derived from the Indian plant Rauxcolfia serpentina, had antipsychotic effects similar to those of chlorpromazine This finding was of interest for two reasons the molecular structure of reserpine has some similarity to that of serotonin and LSD and it was found that reserpine liberates serotonin from presynaptic stores in the CNS and thus produces a short-lived excess supply of functionally available serotonin at the synapse. In the context of a serotonin hypothesis of schizophrenia, it could be postulated that the antipsychotic effect of reserpine was due to its ability to liberate serotonin presynaptically and make it functionally available. However, despite its scientific appeal, the serotonin hypothesis of schizophrenia did not last long because it was in conflict with both psychopathological and pharmacological findings ... 

Unlike reserpine, chlorpromazine has neither a serotonin-like chemical structure nor does it release serotonin from nerve raidings. 

The peak at rn/z610in Figure 5, IB represents those molecules of reserpine which incorporate 1 atom of somewhere in the structure. As there are 33 carbon atoms in reserpine, there is a 33x 1.11 % probability of there being a C atom in any particular molecule of reserpine. which equals 36.6% this explains the intensity of the mfzeiO peak. The peak at nVz 611 represents molecules of reserpine that incorporate two atoms, the peak height is again about 37% of the peak at nyz610 (or 13,4% of the parent peak at rr z 609),... 

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