Morphine skeletal structure

Under consideration here are totally synthetic stripped down morphinelike skeletal structures and even simpler fragments of the morphine molecule, initially actually not recognized as such. These are primarily based on the piperidine ring. 

Compounds isolated from natural sources are frequently optically pure. Thus camphor (11), cholesterol (14), morphine (16), for example, are isolated in the optically pure state. The parent molecule of (13) is D-glucose, and like camphor and cholesterol is readily available in very large quantities. These, and comparable compounds, form what is now described as a chiral pool, i.e. low-cost, readily available, chiral compounds which provide starting materials for conversion into other compounds, of simplified skeletal and functional structure, in which some or all of the chiral features have been retained. 

Many opium-derived and other IQs are psychoactive, the best known being the analgesic, addictive, narcotic, opium-derived morphinan alkaloids codeine and morphine (heroin being the semi-synthetic diacetate of morphine). The tertiary or quaternary amine structural component is important for the activity of some Erytkrina alkaloids and bisbenzyliso-quinolines (notably the major curare component (+)-tubocurarine) as antagonists of the nACh-R involved in neuronal excitation of skeletal muscle. The planar disposition of some polycyclic benzophenanthridines enables intercalation (parallel interleaving) between the base pairs of DNA. A variety of naturally occurring and synthetic IQ compounds are protein kinase inhibitors. 

The NMR spectra of compounds 4-8 were consistent with the structures assigned. This evidence together with the great similarities in UV and IR spectra discussed above clearly established that the degradations had not caused any major skeletal changes. The facile aromatiza-tion characteristic of the morphine alkaloids appears to be blocked in this case by the five-membered ring and spiro carbon atom C-6. This explains the stability of cancentrine methine methiodide to potassium hydroxide and the need for the much stronger base to effect the second elimination to the bismethine 8 (3, 4). 

Friedrich W. Sertiimer (Germany 1783-1841) isolated a compound from opium extracts in 1805 that is now known to be morphine (12). In 1815, Michel E. Chevreul (France 1786-1889) isolated a material from skeletal muscle now known to be creatine (13), which has been used as a dietary supplement despite the observation that it can cause kidney damage and muscle cramping. He also elucidated the structure of simple soaps, which are metal salts of fatty acids (14) and gave the name butyric acid (15) to the carboxylic acid found in rancid butter. 

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