Thebaine structure elucidation

In the first place, the structure of the target molecule is submitted to a rational analysis in order to perceive the most significant structural features, and it may be useful to use different types of molecular models at this point. It should be remembered that a molecular structure has "thousand faces" and finding the most convenient perspective may greatly simplifly the synthetic problem. The synthesis of opium alkaloids, for instance, is much simplified if one realises that they are, in fact, derivatives of benzyltetrahydroisoquinoline (18) (see Scheme 3.8). This was indeed the inspired intuition of Sir Robert Robinson which led to the structural elucidation of morphine (19) and to a first sketch of the biogenetic pathway [22], and later on to the biomimetic synthesis of thebaine 20 [23] [24]. 

Alkaloid isolation and structural elucidation is summarized in Table 6. In addition to known constituents, codeine and neopine have been isolated from Papaver brac-teatum Although callus cells from this plant contain thebaine at early stages of subculturing, only traces are found later. - ° Thebaine was identified among seventeen isoquinoline alkaloids detected in, or isolated from P. syriacum. ... 

In 1803 the German pharmacist Seturner achieved the isolation of morphine as one of the active ingredients of opium. He named the compound after Morpheus, Ovid s god of dreams, the son of sleep. Among the other alkaloids of opium are codeine, isolated in 1832, thebaine, narceine, narcotine, and papaverine. From the isolation of pure morphine to the elucidation of its structure by first Gulland and Robinson(1,2) and later Schopf(3) took another 120 years. A total synthesis by Gates and Tschudi(4,5) confirmed the structure in the early 1950s. 

Bentley and his colleagues7 describe the structure-activity relationships of a wide variety of structures derived from Diels-Alder adducts of thebaine. Among this group are found some of the most potent analgesics known. Particular attention should be directed toward the fine application of nuclear magnetic resonance spectroscopy, by Fulmor and his associates to elucidate the stereochemical configurations of these interesting compounds. 

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