Thiasporine A类似物的设计、合成和抑菌活性

Design,synthesis and fungicidal activities of Thiasporine A analogues

Thiasporine A是从海洋放线菌Actinomycetospora chlora SNC-032代谢物中分离得到一个含有苯基噻唑环结构的天然产物,对肺癌细胞系H2122具有中等毒性。本文以取代苯甲腈为原料合成了Thiasporine A(4o)和29个Thiasporine A类似物(3a~3o,4a~4n),其中24个未见文献报道,利用核磁共振氢谱、碳谱和高分辨质谱对化合物的结构进行了表征,并测定了Thiasporine A及其类似物的抑菌活性。结果表明,在200μmol/L的浓度下,大部分目标化合物对5种供试植物病原真菌均有一定的抑制效果。其中:化合物3e和3i对水稻纹枯病菌Rhizoctonia solani的抑制率分别为84.5%和84.4%,其EC50值分别为17.3μmol/L和21.9μmol/L;化合物4b和4j对白芨白绢病菌Selerotium rolfsii的抑制率为100%;化合物4b对烟草黑胫病菌Phytophthora parasitica抑制率为83.3%,高于商品药剂噻呋酰胺;化合物3g对5种供试病原菌的抑制率都在70%以上。

Thiasporine A was a natural product containing phenylthiazole ring isolated from the marinederived Actinomycetospora chlora SNC-032 and showed cytotoxicity against the lung cancer cell line H2122.Thiasporine A(4o)and 29 Thiasporine A analogues(3a-3o,4a-4n)were synthesized using substituted benzonitriles as starting material,among which 24 analogues have not been reported in literature.Their structures were characterized by 1H NMR,13C NMR and HRMS spectra.The fungicidal activities of Thiasporine A and its analogues were tested.The results indicated that most of Thiasporine A analogues exhibited certain fungicidal activities.Compounds 3e and 3i were found to have the inhibition rates of 84.5% and 84.4% against Rhizoctonia solani at a concentration of 200μmol/L,with the EC50 values of 17.3μmol/L and 21.9μmol/L,respectively.Compounds 4b and 4j displayed the inhibition rate of 100% against Selerotium rolfsii at 200μmol/L.compound 4b demonstrated an inhibition rate of 83.3% against Phytophthora parasitica at 200μmol/L,which was better than the commercial thifluzamide.The inhibition rates of compound 3g against five fungi were all higher than 70%at 200μmol/L.