Kobe Pharmaceutical University, 4-19-1 Motoyamakita, Higashinada-ku, Kobe-shi 658-8558, Japan.
J Nat Prod. 2010 Feb 26;73(2):115-22. doi: 10.1021/np900440d.
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.
证明了具有 D 环上 OH 基团的 2,3,10,11-氧代四氢原小檗碱的代谢途径。研究了麦氏、紫堇属和南天竹属细胞培养物中[13]C-或 D2-标记前体的代谢。通过应用 LC-NMR、LC-MS/MS 和 LC-CD 技术，确定了从喂食实验中获得的生物碱代谢物的结构。（S）-四氢伪原小檗碱（5）在三种植物细胞培养物中立体特异性地 O-甲基化为 S-异构体（12）。该 S-异构体进一步 N-甲基化为（S）-α-N-甲基盐（15），在麦氏和紫堇属细胞培养物中氧化生成伪原小檗碱型生物碱（10）。这些转化与 2,3,9,10-氧代原小檗碱相同。四氢伪原小檗碱（5、6 和 12）分别脱氢生成伪原小檗碱（13、16 和 14）。5 的 R-和 S-对映异构体在麦氏 Cordata 中脱氢不同于 2,3,9,10-氧代原小檗碱的情况。具有 C-10 和 C-11 上 OH 基团的前体 7 在 M. cordata 和 C. ochotensis var. raddeana 中在 C-10 上 O-甲基化，这与 N. domestica 中在 C-11 和 C-10 上均 O-甲基化不同。在 N. domestica 中发生了立体选择性 O-去甲基化[(S)-5 到(S)-18]。
