The first total synthesis of (+)-cytosporolide A was achieved by a biomimetic hetero-Diels-Alder reaction of (-)-fuscoatrol A with o-quinone methide generated from (+)-CJ-12,373. The dienophile, highly oxygenated caryophyllene sesquiterpenoid (-)-fuscoatrol A, was synthesized from the synthetic intermediate in our previous total synthesis of (+)-pestalotiopsin A. The o-quinone methide precursor, isochroman carboxylic acid (+)-CJ-12,373, was synthesized through a Kolbe-Schmitt reaction and an oxa-Pictet-Spengler reaction. The hetero-Diels-Alder reaction of these two compounds proceeded with complete chemo-, regio-, and stereoselectivity to produce the complicated pentacyclic ring system of the cytosporolide skeleton. This total synthesis unambiguously demonstrates that natural cytosporolide A has the structure previously suggested.
1998-02-01·Journal of Antibiotics4区 · 医学
CJ-12,373, a novel topoisomerase II inhibitor: fermentation, isolation, structure elucidation and biological activities
4区 · 医学
作者: Inagaki, Taisuke ; Kaneda, Keiji ; Suzuki, Yumiko ; Hirai, Hideo ; Nomura, Etsuko ; Sakakibara, Tatsuo ; Yamauchi, Yuji ; Huang, Liang H. ; Norcia, Michael ; Wondrack, Lilly M. ; Sutcliffe, Joyce A. ; Kojima, Nakao
A novel isochroman carboxylic acid CJ-12,373 was isolated from Penicillium sp. CL22557. CJ-12,373 inhibits both DNA gyrase-mediated supercoiling and relaxation without the formation of a cleavage intermediate, suggesting that CJ-12,373 inhibits DNA gyrase at a stage distinct from the religation step. CJ-12,373 is not selective for procaryotic DNA gyrase as it also inhibits relaxation mediated by eukaryotic topoisomerase II. The antimicrobial potency of CJ-12,373, however, is largely attributed to its inhibition of DNA gyrase.