Reticuline methochloride

Since it is known that quaternary salts give better yields of phenolic oxidative coupling products than do tertiary bases, when oxidised with one-electron transfer agents in the laboratory, the possible role of reticuline methochloride (tembetarine chloride) in the biogenesis of more complex alkaloids has been examined. The labelled salt has been found to be very poorly incorporated into morphine, sinomenine, and protopine. 

P. somniferum) in this biosynthetic pathway is still obscure. InP. somni-ferum the biosynthesis of morphine can also proceed from (+ )-reticuline provided that this compound is first transformed into (— )-reticuline. The biosynthesis is, however, impossible (via thebaine) from ( + )-reticuline methochloride (52). 

Although in P. somniferum and Sinomenium acutum the biosynthesis of the morphinane bases can be carried out with (+)-reticuline as starting material, these bases and also protopine (101a) cannot be obtained biosyn-thetically in satisfactory yield from (+)-tembetarine chloride (reticuline methochloride). Similar results were obtained with D. spectabilis (683). Important intermediates of the biosynthesis between tetrahydroprotober-berine and protopine alkaloids are the compounds of the dihydroprotopine type (102), which were prepared in high yield by partial synthesis with cyanogen bromide (von Braun method) (684). The biosynthesis of pro topine alkaloids is also discussed in Section III,N. 

Additional results are that (-)-(5)-scoulerine (68) is a precursor for san-guinarine (77) and chelerythrine (78) and labelled (-)-(5)-stylopine (71) is incorporated into coptisine (72). [N-methyl8- H]Stylopine methochloride [as (70)] afforded chelidonine (76) and protopine (73) essentially without change in isotope ratio and must thus be considered as implicated on the pathway to both alkaloids. (The same conclusion for protopine has been reached independently. ) On the other hand radioactive nandinine (79) failed to label chelidonine, stylopine, or protopine, suggesting that the alternative (69) may be an intermediate instead. In agreement with other work (5)-reticuline (67) and (5)-scoulerine (68) were much better precursors than the i -isomers for protopine (73), and incorporation of (68) resulted in complete loss of tritium label from C-14. Allocryptopine (81) was well labelled by radioactive isocorypalmine (82) (which also serves as a precursor for narcotine see below). The combined results lead to the pathways shown in Scheme 3. 

Protopine.—It is known that protopine (94) is elaborated in vivo along a route which involves ( + )-reticuline (82) ° and (-)-scoulerine (91) and, probably, stylopine (92) 110 quaternary salt (93) is also to be included in the pathway, a conclusion which follows from the incorporation into protopine (94), in Corydalis incisa, of [N-Me- Cjtetrahydrocoptisine methochloride [as (93)] without loss of the N-methyl group. " [Label from this salt was not incorporated into corynoline (95).]... 

R )-(—)-Armepavine (7b) was isolated from Rhamnus frangula (Rhamnaceae) (335). The tembetarine chloride [methochloride of reticuline (7f)] was isolated from Fagara naranjillo (Griseb.) (336). 

The biosynthesis proceeds from reticuline via proto-betberine derivatives, e.g., stylopine methochloride. lit. Mothes etal., p. 226-230 Prog. Bot. 51, 113-133 (1980). 

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