By a route described by Jeger et al.<165\ by means of which the c«-con-figuration had been established for rings B and C of morphine, (—)-3-

hydroxy-iV-methylmorphinan (60) was subjected to a Hoffmann degradation. The vinyl compound (150) was converted into the corresponding glycol (151) by treatment with osmium tetroxide. The glycol (151) was then transformed into the aldehyde and reduced by the Wolff-Kishner method. The oxidation of the reduction product with chromic acid led to the 10-keto derivative (154) which was subjected to ozonization. This reaction yielded (—)-cw-[2-methyl-2-carboxy-cyclohexyl-(l)]-acetic acid (155) which was identical with the dicarboxylic acid obtained by the decomposition of the-baine(165) and abietic acid(166).

In this way the relationship of the asymmetric carbon atoms 13 and 14 of the morphinans to those of morphine (156) was unambiguously established and their configuration correlated to glyceraldehyde. According to Stork(167,168) and Rapoport et al.u69> this proof also established the configuration at the asymmetric carbon atom 9 as shown in formula (133).

The (+)-3-hydroxy-iV-methyl-morphinan (158) belonging to the enantiomeric series therefore has the same configuration as sinomenine (157)(167,168) at the carbon atoms 9, 13 and 14.


(156) Morphine

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