Absolute stereochemistry, morphine

The structure of (—)-morphine was established conclusively 10 by X-ray crystallography from two projections of the hydroiodide dihydrate salt and confirmed for codeine and morphine by an X-ray study of their hydrochloride trihydrate salts/111 The piperidine ring was shown to adopt a chair conformation with the N-Me equatorial. The absolute stereochemistry of morphine was also confirmed by X-ray studies/415"417 ... 

The absolute stereochemistry of cancentrinedihydromethine-0-methyl ether (7) has been determined by X-ray analysis of its hydro-bromide 13). The absolute stereochemistry of cancentrine (1) is easily derived from this as the C-9—C-13 ethanamine bridge must necessarily be as-fused. The slight possibility that epimerization at C-14 could have occurred in the conversion 1 7 may be discounted on the basis of past experience 14) with morphine systems. Moreover the hydrogenation of dehydrocancentrine-A to a product consisting mainly of cancentrine indicates that the C-8, C-14 double bond is hydrogenated from the lower side of the molecule since approach to the upper side... 

Morphine is the prototype opioid (Table 24.2). It is selective for p opioid receptors. The structure of morphine is composed of five fused rings, and the molecule has five chiral centers with absolute stereochemistry 5(R), 6(S), 9(R), 13(S) and 4 R). The naturally occurring isomer of morphine is levo-[(-)] rotatory. ( + )-Morphine has been synthesized, and it is devoid of analgesic and other opioid activities (73). 

Scheme 1334. A representation of the final steps in the degradation of ergosterol via A -3P-acetoxy-9a,lla-dioxy-7-ketoergostene to (lf ,25 )-(+)-2-carboxy-2-methylcyclohexane acetic acid, confirming the absolute stereochemistry of codeine (and thus morphine). After Heusser, H. Beriger, E. Anliker, R. Jeger, O. Ruzicka, L. Helv. Chim. Acta, 1953,36,1918.

Morphinan alkaloids are the pharmaceutically most important class of isoquinoline alkaloids. Codeine and morphine are found only in Papaver somniferwn and closely related species. Both alkaloids are derived from (R)-reticuline, the absolute stereochemistry of which corresponds with the configuration of morphinan alkaloids. Re-ticuline is therefore an important branch point in isoquinoline bio nthesis. However, either enantiomer of reticulme, when fed separately, is incorporated into morphinan alkaloids essentially to the same extent. The question therefore arises by which mechanism (R)-reticuline is formed within the plant. 

---