乙酰胆碱酯酶抑制剂Territrem B 类似物的合成新方法

赵金浩; 程敬丽; 赵锋; 朱国念; 王彦广; 赵昱

乙酰胆碱酯酶抑制剂Territrem B 类似物的合成新方法

1.
浙江大学理学院化学系,浙江杭州 310027
2.
浙江大学农药与环境毒理研究所, 浙江杭州 310029
3.
浙江大学药学院, 浙江杭州 310029

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出版历程
- 收稿日期: 2005-07-08
- 修回日期: 2005-10-08

The New Method for the Preparation of Territrem B Analogues as AChE Inhibitors

1.
Department of Chemistry, College of Science, Zhejiang University, Hangzhou 310027, China
2.
Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou 310029, China
3.
College of Pharmaceutical Science, Zhejiang University, Hangzhou 310029, China

摘要

摘要: 设计了一条新的2-烯- 1 -酮-类伊比林-20-基-取代苯甲酸酯( 6 )土震素(Territrem)B类似化合物的合成方法。以甲磺化伊比林醛( 2 )为原料,经脱甲磺酸生成2-烯类伊比林-13-醛( 3 ),化合物 3 经溴代丁二酰亚胺(NBS)光照溴化一步法生成中间产物 4,4 不经分离直接与酚反应生成化合物 5,5 再经一步法水解氧化制得目标产物 6 。该方法不仅提高了 6 的收率(提高5%~30%),还合成了5个新化合物 3和5b~5e 。生物活性测试表明,在10-4 mol/L条件下,只有化合物 6a 对乙酰胆碱酯酶(AChE)显示出17%的抑制活性。
- Territrem B /
- 类似物 /
- 新合成方法 /
- 生物活性
Abstract: Some 2-en-1-one-ebelactonyl-20-yl-benzoyl esters as Territrem B analogues were prepared with new method. Aldehyde 2 was treated with Li2CO3 in N,N-dimethylacetamide (DMAc) to give 2-en-ebelactonyl-13-aldehyde 3 which was oxidation with N-bromosuccinimide (NBS) under irradiation gave the corresponding 2-en-1-bromo-acyl bromide 4 in one step. Then 4 was esterified directly with substituted phenols to afford the corresponding esters 5 in one step. And compound 6 can be prepared from 5 through hydrolysis and oxidation in one step. During these process, the yield of 6 was increased 5%~30% than the original method, and five new compounds 3 and 5b~5e were prepared. Among all of the compounds only 6a showed 17% inhibitory activity to AChE in 10-4 mol/L.
- Territrem B /
- analogues /
- new synthesis method /
- bioactivity 收稿日期: 2005-07-08

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参考文献(12)

Ling K H, Yang C K, Peng F T. Territrems, tremorgenic mycotoxins of Aspergillus terreus[J]. Environ Microbiol, 1979, 37(3): 355-357.

Ling K H, Liou H H, Yang C M, et al. Isolation, chemical structure, acute toxicity, and some physicochemical properties of Territrem C from Aspergillus terreus[J]. Environ Microbiol, 1984, 47(1): 98-100.

Otoguro K, Kuno F, Omura S. Arisugacins, selective acetylcholinesterase inhibitors of microbial origin[J]. Pharmacol Ther, 1997, 76(1): 45-54.

Dowd P F, Peng F C, Chen J W, et al. Toxicity and anticholinesterase activity of the fungal metabolites Territrems to the corn-earworm, Helicoverpa-zea[J]. Entomol Exp Appl, 1992, 65(1): 57-64.

Chen J W, Ling K H. Territrems: naturally occurring specific irreversible inhibitors of acetylcholinesterase[J]. J Biomed Sci, 1996, 3(1): 54-62.

Peng F C. Acetylcholinesterase inhibition by Territrem B derivatives[J]. J Nat Prod, 1995, 58 (6): 857-862.

Chen J W, Luo Y L, Hwang M J, et al. Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism[J]. J Biol Chem, 1999, 274(49): 34916-34923.

Zhao J H, Zhao F, Zhao Y, et al. Synthesis of A/B ring analogs of Territrem B and evaluation of their biological activities[J].Helv Chim Acta, 2004, 87(7): 1832-1853.

Finucane B W, Thomson J B. Direct oxidation of allylic methylene to carbonyl[J]. Chem Comm, 1969,(20): 1220.

Zhao Y, Ku Y L, Hao X J, et al. Preparation of analogues of Territrem B, a potent AChE inhibitor[J]. Tetrahedron, 2000, 56(40): 8901-8913.

Cheung Y F.N-bromosuccinimide:direct oxidation of aldehydes to aclid bromides [J].Tetrahedron Lett, 1979, 20(40):3809-3810.

Ellman G L, Courtney K D, Andres V, et al. A new and rapid colorimetric determination of acetylcholinesterase activity[J]. Biochem Pharmacol, 1961, 7(1): 88-90. (Ed.JIN S H)

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