Biotransformation of phenolic tetrahydroprotoberberines in plant cell cultures followed by LC-NMR, LC-MS, and LC-CD.
A metabolic pathway of 2,3,10,11-oxygenated tetrahydroprotoberberines having the OH group on ring D was demonstrated. Metabolism of (13)C- or D(2)-labeled precursors was studied in cell cultures of Macleaya, Corydalis, and Nandina species. The structures of alkaloid metabolites obtained from feeding experiments were determined by application of combined LC-NMR, LC-MS/MS, and LC-CD techniques. (S)-Tetrahydropseudoprotoberberine (5) was stereospecifically O-methylated to the S-isomer (12) in cell cultures of three plant species. This S-isomer was further N-methylated to the (S)-alpha-N-methyl salt (15), which was oxidized to produce the pseudoprotopine-type alkaloid (10) in cell cultures of Macleaya and Corydalis species. These transformations were the same as those of 2,3,9,10-oxygenated protoberberines. The tetrahydropseudoprotoberberines (5, 6, and 12) were dehydrogenated to pseudoprotoberberines (13, 16, and 14), respectively. Both the R- and S-enantiomers of 5 were dehydrogenated in Macleaya cordata different from the case of 2,3,9,10-oxygenated protoberberines. Precursor 7, with OH groups at C-10 and C-11, was O-methylated at C-10 in M. cordata and C. ochotensis var. raddeana, which was distinct from O-methylation in N. domestica, in which 7 was O-methylated at both C-11 and C-10. Stereoselective O-demethylation [(S)-5 to (S)-18] occurred in N. domestica.
Iwasa
Kinuko
K
Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada-ku, Kobe-shi 658-8558, Japan. k-iwasa@kobepharma-u.ac.jp
Cui
Wenhua
W
Takahashi
Teturo
T
Nishiyama
Yumi
Y
Kamigauchi
Miyoko
M
Koyama
Junko
J
Takeuchi
Atsuko
A
Moriyasu
Masataka
M
Takeda
Kazuyoshi
K
D029061:Annonaceae / Q000737:chemistry; D028141:Berberidaceae / Q000737:chemistry*; D001600:Berberine Alkaloids / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D018929:Cell Culture Techniques; D031310:Fumarioideae / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D028101:Papaveraceae / Q000737:chemistry*; D013237:Stereoisomerism
D001600:Berberine Alkaloids; C009090:protoberberine