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The Biosynthesis of the Cularine Alkaloids
Author(s) -
Mueller Martin J.,
Zenk Meinhart H.
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199319930191
Subject(s) - benzylisoquinoline , chemistry , isoquinoline , stereochemistry , biosynthesis , alkaloid , hydroxylation , metabolite , isomerization , moiety , tyrosine , dopamine , biochemistry , enzyme , biology , catalysis , neuroscience
In order to study the cularine biosynthesis, L ‐[β‐ 13 C]tyrosine ( L ‐ 18 ), [α‐ 13 C]tyramine ( 20 ), L ‐[3′‐ 18 O]DOPA ( L ‐ 19 ) and [α‐ 13 C, 3′‐ 18 O]dopamine ( 21 ) were synthesized and fed to Corydalis claviculata and Sarcocapnos crassifolia plants, which are rich sources of cularine‐type alkaloids. ( S )‐Crassifoline [( S )‐ 15 , an established cularine ( 1 ) precursor] and cularine‐type alkaloids subsequently isolated, showed upon L ‐[β‐ 13 C]tyrosine feeding approximately equal labeling (1:0.8) of the isoquinoline and benzyl moiety, whereas the other precursors were solely incorporated into the isoquinoline half, indicating that three of the four oxygen functions present in cularine‐type alkaloids are derived from simple, early precursors. The fourth oxygen atom appears to be introduced later into a trioxygenated alkaloidal intermediate. [α‐ 13 C, 3‐ 18 O]Dopamine was incorporated into the upper half of the 7,8‐oxygenated ( S )‐crassifoline [( S )‐ 15 ] molecule, without loss of 18 O‐label. This fact excludes an isomerization mechanism of 6,7‐oxygenated isoquinolines through a dehydroxylation/hydroxylation step. Furthermore, these findings proved to be correct by separate feeding experiments with a novel 3′,7,8‐trihydroxylated ( S )‐tetrahydrobenzylisoquinoline [( S )‐ 10 ] and its 3′,6,7‐trihydroxylated isomer, ( S )‐norcoclaurine [( S )‐ 9 ], the common precursor of benzylisoquinoline alkaloids in nature. The first alkaloid was exclusively biotransformed into ( S )‐crassifoline [( S )‐ 15 ] and cularine‐type alkaloids, whereas ( S )‐norcoclaurine [( S )‐ 9 ] was only metabolized to its well established metabolite, ( S )‐reticuline [( S )‐ 16 ], but not to cularine‐type alkaloids. Feeding experiments with ( S )‐ and ( R )‐[1‐ 13 C]norjuziphine [( S )‐ 11 , ( R )‐ 11 ], ( RS )‐[ N ‐ 13 C]juziphine [( RS )‐ 13 ], ( RS )‐[ N ‐ 13 C]3′‐hydroxyjuziphine [( RS )‐ 14 ] and ( RS )‐[ N ‐ 13 C]crassifoline [( RS )‐ 15 ] confirmed a new pathway to ( S )‐crassifoline and the ( S )‐configurated cularine‐type alkaloids 1 – 5 , and showed in addition that there must be at least one enzyme in the pathway which is ( S )‐stereospecific.