短指软珊瑚Sinularia sp.的多骨架类型萜类成分和生物活性研究

Study on terpenes with diverse skeletons from soft coral Sinularia sp.and their bioactivities

目的对采自中国南海的短指软珊瑚Sinularia sp.萜类化学成分和生物活性进行研究。方法综合利用薄层色谱、硅胶柱色谱、凝胶柱色谱、半制备HPLC等分离手段进行纯化,结合NMR和MS等波谱数据分析及比对文献数据,开展化合物的结构鉴定。结果从短指软珊瑚Sinularia sp.中共分离鉴定了15个化合物,包括5个倍半萜:1β-hydroxy-4(15),5E,10(14)-germacratriene(1)、(7R^(*))-opposit-4(15)-ene-1β,7-diol(2)、15-hydroxy-α-cadinol(3)、nephalbidol(4)和isodauc-6-ene-10β,14-diol(5);1个单萜:pubinernoid A(6);8个降二萜:norcembrene 5(7)、norcembrenolide 2(8)、sinularcasbane O(9)、scabrolide D(10)、5-epi-sinuleptolide(11)、sinuleptolide(12)、ineleganolide(13)和yonarolide(14);1个二萜:dihydrosinularin(15)。结论化合物3和6为首次从软珊瑚科软珊瑚中分离得到,1、2和5为首次从短指属软珊瑚中分离得到。倍半萜1~5分别隶属于大根香叶烷、oppositane、杜松烷、愈创木烷和异胡萝卜烷共5种不同骨架类型,单萜6隶属于罕见的反Bredt规则的双环桥烯型骨架,降二萜7~14分别隶属于降西松烷、inelegane和yonarane共3种不同骨架类型,二萜15隶属于西松烷骨架。活性测试时,化合物1~6对人肺腺癌A549、人结肠癌HT-29、人肝癌SNU-398、人胰腺癌Capan-1细胞株均未表现明显的细胞毒活性,化合物7~15对乙酰辅酶A羧化酶1与ATP-柠檬酸裂解酶均未有明显的酶抑制活性。

Objective To investigate the terpene-type chemical constituents and bioactivities of soft coral Sinularia sp.collected from South China Sea.Methods The isolation and purification of these compounds were performed by thin-layer chromatography,silica gel column chromatography,Sephadex LH-20 column chromatography and semi-preparative HPLC.Their structures were characterized by analysis of NMR and MS data and comparison with the data reported in literature.Results Fifteen known compounds with diverse skeletons were isolated from the soft coral Sinularia sp.,including five sesquiterpenes:1β-hydroxy-4(15),5E,10(14)-germacratriene(1),(7R*)-opposit-4(15)-ene-1β,7-diol(2),15-hydroxy-α-cadinol(3),nephalbidol(4),isodauc-6-ene-10β,14-diol(5);one monoterpene:pubinernoid A(6);eight norditerpenoids:norcembrene 5(7),norcembrenolide 2(8),sinularcasbane O(9),scabrolide D(10),5-epi-sinuleptolide(11),sinuleptolide(12),ineleganolide(13),yonarolide(14);one diterpenoid:dihydrosinularin(15).Conclusion Compounds 3 and 6 are isolated from the family Alcyoniidae for the first time,while compounds 1,2 and 5 are isolated from the genus Sinularia for the first time.Among them,sesquiterpenes 1—5 possessed five different skeletons including germacrane,oppositane,cadinane,guaiane and isodaucane;Monoterpene 6 was a rare anti-Bredt bridgehead bicycloalkene;Norditerpenoids 7-14 belonged to three different carbon frameworks including norcembrane,inelegane and yonarane;diterpene 15 is a cembranoid.In the bioassays,compounds 1-6 did not exhibit potent cytotoxicity against A549,HT-29,SNU-398 and Capan-1 cell lines,and compounds 7-15 showed no significant inhibitory activity against acetyl-CoA carboxylase and ATP citrate lyase.