Biosynthesis Berberine

biosynthesis of berberine

the alkaloid berberine has tetracyclic skeleton derived benzyltetrahydroisoquinoline system incorporation of carbon atom provided s-adenosyl methionine (sam) via n-methyl group. formation of berberine bridge readily rationalized oxidative process in n-methyl group oxidized iminium ion, , cyclization aromatic ring occurs virtue of phenolic group.

reticuline known immediate precursor of protoberberine alkaloids in plants. berberine alkaloid derived tyrosine. l-dopa , 4-hydroxypyruvic acid both come l-tyrosine. although 2 tyrosine molecules used in biosynthetic pathway, phenylethylamine fragment of tetrahydroisoquinoline ring system formed via dopa, remaining carbon atoms come tyrosine via 4-hydroxyphenylacetaldehyde. l-dopa loses carbon dioxide form dopamine 1. likewise, 4-hydroxypyruvic acid loses carbon dioxide form 4-hydroxyphenylacetaldehyde 2. dopamine 1 reacts 4-hydroxy-phenylacetaldehyde 2 form (s)-norcolaurine 3 in reaction similar mannich reaction. after oxidation , methylation sam, (s)-reticuline 4 formed. (s)-reticuline serves pivotal intermediate other alkaloids. oxidation of tertiary amine occurs , iminium ion formed 5. in mannich-like reaction ortho position phenol nucleophilic, , electrons pushed form 6. product 6 undergoes keto-enol tautomerism form (s)-scoulerine, methylated sam form (s)-tetrahydrocolumbamine 7. product 7 oxidized form methylenedioxy ring ortho-methoxyphenol, via o2-, nadph- , cytochrome p-450-dependent enzyme, giving (s)-canadine 8. (s)-canadine oxidized give quaternary isoquinolinium system of berberine. happens in 2 separate oxidation steps, both requiring molecular oxygen, h2o2 , h2o produced in successive processes.