13-Hydroxy protoberberines

A patent that covers the synthesis of 13-hydroxy-protoberberines by conventional Mannich cyclization of benzylisoquinolines with formaldehyde has been published. ""... 

C-9, and C-10, always with a phenolic hydroxy group at the 8a position. Moreover, they differ from one another by the oxidation state of the benzylic C-13 as well as by substitution and degree of saturation of the isoquinoline fragment. These alkaloids, classified as benzylisoquinoline alkaloids (2,70-74), have recently been called by Shamma et al. (75-77) pseudobenzyliso-quinolines originating from protoberberine alkaloids. In Table V a list of 8,8a-secoberbine alkaloids, sources, and spectral data are presented. 

Protoberberine Alkaloids.—In the course of the bioconversion of the proto-berberine scoulerine (65) into chelidonine (62) and phthalide-isoquinolines, e.g. narcotine (63), C-13 becomes oxidized.61 Ophiocarpine (68), with a hydroxy-group at C-13, represents an intermediate stage in the modification of the protoberberine skeleton, and results62 of tracer experiments have shown that scoulerine (65) is also to be included in the biosynthesis of this alkaloid. Tetrahydro-protoberberine (67) is also a precursor, its incorporation indicating that C-13 hydroxylation is a terminal step. As for other protoberberine derivatives,63 nandinine (64) was not assimilated,62 and it follows then that (65) is probably converted into (67) by way of isocorypalmine (66). 

The structure of corydalmine as 10-hydroxy-2,3,9-trimethoxy-dibenzo[agf]quinolizidine (XLV) was proposed by Imaseki and Taguchi after comparisons of ( )-corydalmine (mp 213°-215°) with the known protoberberine isomers, ( + )-tetrahydrojatrorrhizine [( + )-corypalmine] (XLII), (+ )-tetrahydrocolumbamine [( + )-isocorypalmine] (XLIII), and (+ )-tetrahydropalmatrubine (XLIV) had revealed its nonidentity with these bases. 

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