Laudanosoline oxidative coupling

Fig. 3. Oxidative coupling products of methylated derivatives of laudanosoline (77, R = H). See Table 8.

Extension of oxidative coupling of laudanosoline by Harley-Mason (20), who investigated the oxidation of tetrahydropapaveroline (27) with potassium ferri-cyanide, afforded 2,3,9,10-tetrahydroxy-5,6-dihydrodibenzopyrrocoline (28) in... 

Oxidative coupling of (5)-(-)-laudanosoline (5) with horseradish peroxidase in the presence of hydrogen peroxide, studied by Brossi et al. (27), afforded dibenzopyrrocoline (—)-6 in 81% yield, and conversion to (5)-(—)-0-meth-ylcryptaustoline (14) by methylation provided additional proof for the absolute configuration of this and related alkaloids. Enzyme specificity in the C— coupling reaction was demonstrated with similar oxidation of (/ )-(—)-laudanosoline methiodide, which afforded an aporphine converted by O-meth-ylation to (R)-(-)-glaucine. 

Additional oxidative coupling processes among the various methylated derivatives of laudanosoline yield many other families of bases, including the pavine argemonine (88) from Argemone mexicana E berberine (89) from Hydrastis canadensis E which, despite its toxicity, has been used as an antimalarial protopine (90) and chelidonine (91) from Chelidonium majus E rhoeadine (92) and the cephalotaxus ester harringtonine (93) from Japanese plum yews ( Cephalotaxus spp.), which is a compound of some significance because it possesses potent antileukemic activity (see Fig. 3). 

Oxidative coupling of phenols. (IR)-(-)-Laudanosolin methiodide mixed with horseradish peroxidase in water, treated during 1 hr. with 0.02%-HgOg while maintaining neutral pH by addition of 0.1 M triethylamine, and acidified with dil. HCl quaternary aporphine deriv. Y 60-90%. 

Early attempts to simulate the synthesis of the aporphine and morphine alkaloids often met with failure. Efforts to oxidize laudanosoline (30), for example, did not give the desired type of coupling, but resulted in the formation of dibenzopyrrocoline structures (Fig. 32.30) (Elliott, 1987 Geissman and Crout, 1969). Alkaloids of this general structure were discovered in the Australian plant Cryptocarya bowiei (Lauraceae). Among these were cryptaustoline (91) and cryptowolline (92). 

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