Laudanosoline methiodide

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. 

More recently, the preparative value of VOCl3 and VOF3-TFA in chemical oxidation has been demonstrated (see Section III, on the pro-aporphine and promorphinane alkaloids) (415,462). Some other authors used the purified enzyme horseradish peroxidase (463). By this method the aporphine base (besides the quaternary dibenzopyrrocoline) is readily obtained from (S)-( + )-laudanosoline hydrobromide or from (/ )-(—)-laudanosoline methiodide with retention of the absolute configuration. The synthesis of 6a,7-dehydroaporphine bases was also carried out by making use of the benzyne reaction (439). Reduction of these substances affords the corresponding aporphine bases (439). The synthesis of isoquinoline alkaloids by lead tetraacetate oxidation was reviewed by Umezawa and Hoshino (343). 

In certain cases, enzymatic coupling of tetrahydrobenzylisoquinolines can be as efficient as purely chemical methods in the preparation of aporphines. Horseradish peroxidase coupling of ( + )-laudanosoline methiodide (27) at neutral pH yielded a 607o yield of the corresponding aporphine. The reaction proceeds with retention of configuration. ... 

Laudanosoline methiodide allowed to react with aq. ferric chloride soln. aporphine derivative. Y 60%. B. Franck, G. Blaschke, and G. Schlingloff, Tetrah. Let. 1962, 439 A. 659, 123 (1962). 

It is well known that the attempts to transform laudanosoline (199, 200) or iV-norlaudanosoline (201) into aporphine bases by oxidation have failed instead compounds with a dibenzopyrrocoline structure (CXXXIX) were obtained. Franck and Schlingloff (202) found that if the reactivity of the nitrogen atom is eliminated by quaternization, then the mild oxidation of laudanosoline methiodide (CXL) with ferric chloride in aqueous solution affords in 60% yield the aporphine base... 

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%. 

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