From Protopines

The unusual alkaloid 13j8-hydroxystylopine was synthesized from protopine which was first converted to dihydrocoptisine. Enamine oxidation then afforded the corresponding phenolbetaine which, upon reduction with sodium boro-hydride, provided exclusively 13jS-hydroxystylopine  

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The proeess used is analogous with that adopted for the sjmthesis of eryptopine (p. 298). The methyl ester of JV- -piperonylethyl-3 4-methy-lenedioxyAomophthalamie acid (I), was treated with phosphoryl ehloride and so eonverted into 2 3 9 10-6wmethylenedioxyoxyprotoberberine (II), which was reduced electrolytically to 2 3 9 10-6ismethylene-dioxytetrahydroprotoberberine (III), of which the methochloride (IV) is identical with wodihydroprotopine chloride, which can be prepared from protopine as already stated above. 

Oxidation of dihydrocoptisine (124), derived from protopine, with m-chloroperbenzoic acid in dichloromethane afforded coptisinephenolbetaine (125) as the hydrochloride in 78% yield (Scheme 26) (82). This oxidation method was applied to dihydroberberine (90) to produce berberinephenolbetaine (121) (53). Additionally, photooxygenation of 90 in methanol containing Rose Bengal gave 121 in 80% yield, further photooxygenation of which led to the epidioxide 122, a 1,3-dipolar cycloaddition product with oxygen (84,85). 

Another possibility might be that the rhoeadine alkaloids arise from protopine alkaloids (see Scheme 20) which are always found present in the plants of the genus Papaver. 

Scheme 29a. Synthesis of ( )-13p-hydroxystylopine (70b) from protopine (101a) (122). Path a, b, in vacuo c, m-chloroperbenzoic acid d, O2 e, NaBH4.

Allocryptopine, C21H23O6N, like protopine occurs in two allotropic modifications, the a-form melting at 160° and the /3-form melting at 170°. The older names of and 7-homochelidonine were based upon an assumed relation to chelidonine and are no longer acceptable. It is readily separable from protopine, with which it is nearly always associated, by reason of the fact that its hydrochloride and nitrate are readily soluble in water. It may also be separated from many associated alkaloids by extracting an aqueous solution of their hydrochlorides with chloroform (34). The protopine alkaloids remain in the aqueous phase. 

Tanahashi, T. and M. H. Zenk, One step enzymatic synthesis of dihydrosanguinarine from protopine. Tetrahedron Lett., 29, 5625-5628 (1988). 

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