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

Kenichi Takao, Shuji Noguchi, Shu Sakamoto, Mizuki Kimura, Keisuke Yoshida, Kin Ichi Tadano

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)15971-15977
Number of pages7
JournalJournal of the American Chemical Society
Volume137
Issue number50
DOIs
Publication statusPublished - 2015 Dec 23

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Biomimetics
Cycloaddition Reaction
Carboxylic Acids
Skeleton
Stereoselectivity
Regioselectivity
Carboxylic acids
quinone methide
cytosporolide A
CJ 12373
caryophyllene
pestalotiopsin A

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Total Synthesis of (+)-Cytosporolide A via a Biomimetic Hetero-Diels-Alder Reaction. / Takao, Kenichi; Noguchi, Shuji; Sakamoto, Shu; Kimura, Mizuki; Yoshida, Keisuke; Tadano, Kin Ichi.

In: Journal of the American Chemical Society, Vol. 137, No. 50, 23.12.2015, p. 15971-15977.

Research output: Contribution to journalArticle

Takao, Kenichi ; Noguchi, Shuji ; Sakamoto, Shu ; Kimura, Mizuki ; Yoshida, Keisuke ; Tadano, Kin Ichi. / Total Synthesis of (+)-Cytosporolide A via a Biomimetic Hetero-Diels-Alder Reaction. In: Journal of the American Chemical Society. 2015 ; Vol. 137, No. 50. pp. 15971-15977.
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