Codeine structural elucidation

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. ... 

Morphine (10) and codeine (11), constituents of opium, are the most interesting alkaloids found in nature. Morphine is also the oldest alkaloid isolated, in 1805, by the German pharmacist Sertiimer from opium, the sun dried latex of Papaver somniferum. The structure of morphine with its so-called morphinan skeleton, once called the acrobat under the alkaloids, was finally elucidated in 1952 by the first total synthesis performed by Gates and Tschudi. Many syntheses would follow [26], but all morphine used today, whether legal or illicit, originates in the natural source P. somniferum or its extract, opium. The latex may contain up to 20% morphine. Most legal morphine is converted into the anticough medicine codeine (Table 5.1) by treatment with trimethylanilinium methoxide, whereas almost all illicit morphine is acetylated to the diacetate heroin. 

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. 

Alkaline degradation of codeine methiodide affords a-codeimethine [xxi] [185, 285], which can be isomerized by alcoholic alkali to /3-codeimethine [xxn] [187, 286-7], also obtainable by the degradation of neopine [xm] methiodide [271]. The degradation of codeine ethiodide follows a similar course [288]. These bases suffer dehydration and loss of the basic side-chain when heated with acetic anhydride and sodium acetate (when acetylmethylmorphol [xxm] is formed [187, 289-90]), and when subjected to further Hofmann degradation (which leads to methylmorphenol [xxiv] [290-2]). The resulting aromatic phenan-threne derivatives are of considerable importance in the elucidation of the basic structure of the morphine alkaloids and are discussed in detail in Chapter XXVII. 

Other alkaloids were extracted soon after. Brucine (1819), pipeline (1819), caffeine (1819), colchicine (1820) and coniine (1826), codeine (1832), atropine (1833), papaverine (1848), " were subsequently obtained. These first isolations were coincidental with the advent of the percolation process for the extraction of drugs. Coniine was the first alkaloid to have its structure established (Schiff, 1870) and to be synthesized, but for others, such as colchicine, it was well over a century before the structures were finally elucidated. 

Similarly the class of nitrogen- and oxygen-containing organic bases isolated from plants and known as alkaloids (e.g. morphine, codeine, nicotine, quinine) was recognized in the early part of the century, and a number of pure alkaloids were isolated, but their structures defied elucidation for some time. Many of these natural products, particularly... 

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