Total Synthesis of (+)-Cytosporolide A via a Biomimetic Hetero-Diels–Alder Reaction

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• 作者：Ken-ichi Takao ; Shuji Noguchi ; Shu Sakamoto ; Mizuki Kimura ; Keisuke Yoshida ; Kin-ichi Tadano
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：December 23, 2015
• 年：2015
• 卷：137
• 期：50
• 页码：15971-15977
• 全文大小：607K
• ISSN：1520-5126

文摘

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.