Transformation of Protoberberines to Related Alkaloids

13-Methylberberine (207) was easily converted to the enamine 208, photolysis of which afforded the two carbinolamines 209a and 209b (124). On exposure to sodium cyanide the mixture was converted to the desired cyanide 210 after separation. Successive oxidation of 210 with potassium ferricyanide 

The same corynoline analog (214) was obtained more conveniently through photolysis in the presence of nitrosobenzene. Addition of nitrosobenzene to 208 from the opposite side of the methyl group resulted in the B/C-trans adduct 215. Reduction of 215 with sodium borohydride followed by acidic treatment gave the B/C-cis product 217 via 216. Hydroxylation of 217 with performic acid and hydrogenolysis of the diol 218 completed the synthesis of 214 (126). 

Lead tetraacetate oxidation was applied to construct a benzo[c]-phenanthridine skeleton. The Hofmann degradation product 224 derived from the phenolic protoberberine 59a was oxidized with lead tetraacetate to afford the p-quinol acetate 225, which was cyclized to the benzo[c]- 

Lithium aluminum hydride reduction of oxychelerythrine (232) gave 6-hydroxydihydrochelerythrine (235), recrystallization of which in methanol afforded 6-methoxydihydrochelerythrine (agoline) (236). Both compounds have been isolated from plants, but they are probably artifacts arising during isolation. On reduction with sodium borohydride or dehydration with 10% hydrochloric acid, 235 was converted to dihydrochelerythrine (203) or chelerythrine (205), respectively (130,131). 

Similarly, berberine (15) was readily converted to (+)-homochelidonine (264), (+)-chelamidine (262), chelerythrine (205), and dihydrochelerythrine (203) (141). According to this method both hexahydro and fully aromatized benzo[c]phenanthridine alkaloids can be readily synthesized via a common intermediate (e.g., 260). 

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Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

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