Total synthesis of antibiotic pestalone by using novel pathway

ORGN 704

Yudao Ma, ydma@sdu.edu.cn1, Yongchang Chen, ycchen54@ujs.edu.cn2, Zhijun Sun, szj5183@yahoo.com.cn1, Qiang Chai, qiangchai@hotmail.com3, Minghu Huang, huangmhhjy@yahoo.com.cn1, Changqin Ma, ydma@sdu.edu.cn1, Xi Fang, ydma@sdu.edu.cn1, and Chun Song, chunsong@sdu.edu.cn4. (1) Chemistry Department, Shandong University, Shanda SouthRoad #27, Jinan, Shandong, 250100, P. R. China, Jinan, 250100, China, (2) Medicinal School, Jiangsu University, Yizhen Road #5, Zhenjiang, 212001, China, (3) Chemistry Department, Shandong Academy of Medical Science, Jing 10 road, Jinan, Shandong, 250062, P. R. China, Jinan, China, (4) Chemistry College, Shandong University, Shanda SouthRoad #27, Jinan, 250100, China
Today, development of resistance to current antibiotics continues to be significant problem in treatment of infectious disease and discovery new effective series antibiotic keeps high priority in the drug discovery. In 2001, Fenical reported new benzophenone antibiotic, Pestalone, exhibits potential antibacterial activity agaist drug-resistant bacteria. Pestalone (1) was isolate as yellow crystals, which showed molecular ions at m/z 438 by LREIMS. Its structure is relatively rare and unrelated to most other natural product although compounds with demethyl at C-20 reported inhibitor of enzyme testosterone-5 –reductase. Pestalone(1) was found to exhibit moderate in vitro cytotoxicity in human tumor cell line with GI50 equals 6.0 uM. Important data showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL). These data suggest Pestalone keeping potential activity for treatment of infectious disease. Herein first straight forward total synthesis of Pestalone was reported under mild condition.

 

Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006