Codeine alkaloids, total synthesis

Rice, K.C. (1980) Synthetic Opium Alkaloids and Derivatives. A Short Total Synthesis of (ib)-Dihydrothebainone, ( )-Dihydrocodeinone, and ( )-Nordihydrocodemone as an Approach to a Practical Synthesis of Morphine, Codeine, and Congeners. Journal of Organic Chemistry, 45, 3135-3137. 

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. 

Keywords Alkaloids Analgesia Codeine Demethylation Morphine Total synthesis... 

Morphine (1) and its congeners, codeine (2), thebaine (3), and oripavine (4), Fig. 1, as well as other minor constituents of the opium poppy latex, continue to gamer interest of the chemical community for a number of reasons. The focus on the total synthesis of these alkaloids in the academic sector has not waned and now spans almost 60 years since the seminal disclosure of the first synthesis by Gates in 1952 [1,2]. 

The summary of accomplishments in the total synthesis of morphine alkaloids is depicted in Table 3. Most authors target codeine as the ultimate S3mthetic target its attainment represents a formal total synthesis of morphine as Rice demonstrated its conversion to morphine by O-demethylation with BBr3 [55]. Such a strategy has... 

Rice KC (1980) Synthetic opium-alkaloids and derivatives - a short total synthesis of (-1-/—)-dihydrothebainone, (+/—)-dihydrocodeinone, and (-f/—)-nordihydrocodeinone as an approach to a practical synthesis of morphine, codeine, and congeners. J Org Chem... 

Reserpine a challenge for total s5mthesis of natural products 05CRV4671. Stereo-controlled construction of quaternary carbon stereocenters in total synthesis of complex cydotiyptamine alkaloids 07AG(E)5488. S5mtheses of morphine and codeine (1992-2002) 06COS99. 

White JD, Caravatti G, Kline TB, Edstrom E, Rice KC, Brossi A (1983) Biomimetic total synthesis of (-)-codeine.Tetrahedron 39 2393-2397 Windholz M (1984) The Merck Index, 10th edn. Merck, Rahway NJ, no 6728 Wright CRA (1874) On the action of organic adds and their anhydrides on the natural alkaloids Part I. J Chem Soc 27 1031-1043... 

A total of more than 20 total syntheses have been described which aim to generate the most important members of the morphinan-type alkaloids, morphine and codeine. These long-standing efforts in alkaloid synthesis have been primarily due to the exceptional pharmacological importance of both compounds, as the most efficacious therapies for pain and cough, respectively. 

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