Zhang Chao, Sun Xian, Xu Shao Hua, Yu Bo Yang, Zhang Jian
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 210009, China.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.
Appl Biochem Biotechnol. 2017 Nov;183(3):1026-1034. doi: 10.1007/s12010-017-2480-x. Epub 2017 Apr 28.
Colchicinoids and their derivatives are of great importance in pharmaceutical applications, and colchicine is usually used as the first choice for the treatment of gout. To expand the structural diversities and clinical application of colchicinoids, many attempts have been established for the derivatives with better activity or less toxicity. Herein, in this paper, we report a direct microbial transformation of colchicine into 2-O-demethyl-colchicine (M1) and 3-O-demethl-colchicine (M2) by Streptomyces griseus ATCC 13273. It is noteworthy that when DMF was used as co-solvent, the yield of M1 and M2 could reach up to 51 and 31%, respectively. All the structures of the metabolites were elucidated unambiguously by ESI-MS, H-NMR, C-NMR, and 2D-NMR spectroscopy.
秋水仙素类化合物及其衍生物在药物应用中具有重要意义，秋水仙碱通常被用作治疗痛风的首选药物。为了扩大秋水仙素类化合物的结构多样性和临床应用，人们已经进行了许多尝试来制备活性更高或毒性更低的衍生物。在此，我们报道了灰色链霉菌ATCC 13273将秋水仙碱直接微生物转化为2-O-去甲基秋水仙碱（M1）和3-O-去甲基秋水仙碱（M2）的过程。值得注意的是，当使用N,N-二甲基甲酰胺作为共溶剂时，M1和M₂的产率分别可达51%和31%。所有代谢产物的结构均通过电喷雾质谱、氢核磁共振、碳核磁共振和二维核磁共振光谱进行了明确的鉴定。
