Qin Bin, Li Yuxin, Meng Lingxin, Ouyang Jingping, Jin Danni, Wu Lei, Zhang Xin, Jia Xian, You Song
School of Life Science and Biopharmaceutical Sciences and ‡School of Pharmaceutical Engineering, Shenyang Pharmaceutical University , Shenyang 110016, People's Republic of China.
J Nat Prod. 2015 Feb 27;78(2):272-8. doi: 10.1021/np500864e. Epub 2015 Feb 13.
The sesquiterpenoid curdione is one of the main bioactive components in the essential oil of Rhizoma Curcumae (Curcuma wenyujin, Curcuma phaeocaulis, and Curcuma kwangsiensis), which has been clinically used for the treatment of cancer in mainland China. Recently it was reported that natural curdione could be hydroxylated by Aspergillus niger and transferred to its corresponding curcumalactones under acidic conditions. Based on this study, the development of a sesquiterpenoid library through the "mirror-image" manipulation of bioactive (non)natural curdione scaffolds by chemical and biological approaches is presented herein. A. niger induced the hydroxylation of two pairs of curdione enantiomers, yielding the corresponding mirror-image hydroxylated curdiones. Simultaneously, the acid-mediated intramolecular "ene" rearrangements of these curdiones and hydroxylated curdione enantiomers yielded the corresponding mirror-image curcumalactones and hydroxylated curcumalactones. Among the 16 pairs of enantiomers obtained in this study, 23 compounds are new sesquiterpenoids. These curdione and curcumalactone derivatives are of particular interest, as they have the potential to be used as lead compounds and scaffolds in drug discovery.
倍半萜莪术二酮是莪术（温郁金、蓬莪术和广西莪术）挥发油中的主要生物活性成分之一，在中国内地已被临床用于治疗癌症。最近有报道称，黑曲霉可使天然莪术二酮羟基化，并在酸性条件下将其转化为相应的莪术内酯。基于该研究，本文介绍了通过化学和生物学方法对生物活性（非）天然莪术二酮支架进行“镜像”操作来开发倍半萜类化合物库的过程。黑曲霉诱导了两对莪术二酮对映体的羟基化，生成了相应的镜像羟基化莪术二酮。同时，这些莪术二酮和羟基化莪术二酮对映体的酸介导分子内“烯”重排产生了相应的镜像莪术内酯和羟基化莪术内酯。在本研究获得的16对对映体中，有23种化合物是新的倍半萜类化合物。这些莪术二酮和莪术内酯衍生物特别令人感兴趣，因为它们有可能用作药物发现中的先导化合物和支架。
