ISSN:
0170-2041
Keywords:
Alkaloids
;
Benzylisoquinoline
;
Biosynthesis
;
Cularine
;
Crassifoline
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
In order to study the cularine biosynthesis, L-[β-13C]tyrosine (L-18), [α-13C]tyramine (20), L-[3′-18O]DOPA (L-19) and [α-13C, 3′-18O]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-13C]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-13C, 3-18O]Dopamine was incorporated into the upper half of the 7,8-oxygenated (S)-crassifoline [(S)-15] molecule, without loss of 18O-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)-[1-13C]norjuziphine [(S)-11, (R)-11], (RS)-[N-13C]juziphine [(RS)-13], (RS)-[N-13C]3′-hydroxyjuziphine [(RS)-14] and (RS)-[N-13C]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.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jlac.199319930191
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