Biosynthesis of Morphine HO HO morphine M-Tyrosine fed to wo{ d oh COOH opium poppy seedlings ¢ hydroxylase Mi, tyrosine oO, Iflabeled DOPA is fed only one label is found, / bie ma HO- H, HO- CH, o eH X b HO. y HO NH, ‘ Mannich + Arom. Subst. dopamine * —-—~—> [thebaine Se Cl ZN sam NH eH fe H O FAD Ne) O codeine MeO” papaverine Ho norlaudanosoline ere (inall poppies) g g%HO, MeO. MeO. / Wt CD ik ~ DN “CH, i-th, HO’ A MeO’ ly MeO’ l Ho ; \ sam 0. Q ap MeO. . Ho Y Meo’ Meo’ norlaudanosoline laudanosine papaverine SAM Norlaudanosolineis incorporated into papaverine and thebaine at a higher rate than tyrosine - it’s closer. HO. MeO. N-CH, CI Ho” 7 4 i HO & 4 Ho , \ sam HO C) Ho” 7 Meo laudanosoline (-Jreticulene | Inaseparate set of experiments, itcan be shown that the methyl groups originate from methionine (Clabeled CH) and hence SAM.one electron oxidation of phenol Seep mma aed dials mon radical MeO. ‘coupling satin nl iat Meo” \* ()sticuine saudi stereospecific 5,2’ nucleophilic anack with reducion ofp | NADPH ‘acetate as leaving group carbonyl wo. Meo. MeO. on ° cazynic yo od ||| oa a Raw | Da it i ofore 4 en Meo" W Hl thebaine S OAc exericaion provides. OH demetination of hebine beter leaving 047 satin via lydrxpation, cleaving planer) Jo denethsaion HO. Ho. = demethsaion o Co @ == ||| NMe ~nMte Nate i h 0’ Meo’ 0’ eopinone cxipavine ‘morpinone apap aye | Sanam peo ne v4 | sion ‘arbors ae nage of ormaldelyde Ho, 0 a: NMe HO" covkinone carbons xine woiee Ex: saltaridine saltaridiol 7-O-acetyransferase EX sluandi “oxidoreductase ‘cosine reductase