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


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.

DOI: 10.1021/jacs.5b11438

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@article{Takao2015TotalSO, title={Total Synthesis of (+)-Cytosporolide A via a Biomimetic Hetero-Diels-Alder Reaction.}, author={Ken-Ichi Takao and Shuji Noguchi and Shu Sakamoto and Mizuki Kimura and Keisuke Yoshida and Kin-ichi Tadano}, journal={Journal of the American Chemical Society}, year={2015}, volume={137 50}, pages={15971-7} }