Isolation and characterization of related impurities in andrographolide sodium bisulphite injection†
Ji-Qin Hou, Bao-Lin Wang, Xiao-Jun Huang, Xiao-Qi Zhang, Guo-Qiang Li, Hao Wang, Wen-Cai Ye, Ping Li
Andrographolide sodium bisulphite (ASB) injection was widely used in China for the treatment of infectious diseases. The chemical analysis of ASB injection resulted in the isolation of four new related impurities (2, 3, 5, 6), together with two known compounds (1, 4). The structures of the new compounds were elucidated by 1D and 2D NMR, high-resolution mass spectrometry, Mo2(OAc)4-induced circular dichroism and ECD calculation. Among them, 1 and 2 were two unprecedented photocyclization derivatives of isocopalane diterpene. The generation of the primary impurity 1 was proved to be an intramolucular 6-exo carbonyl radical cyclization of ASBthrough a novel sulfonyl group transfer. This finding furnished a facile photocyclization methodology to afford 1 in good yield with excellent regioselectivity. The possible mechanism for the formation of the related impurities was also discussed.
Circular dichroism, Absolute configuration, Medicinal