Convergent total synthesis of gymnocin-A and evaluation of synthetic analogues

Chihiro Tsukano, Makoto Ebine, Makoto Sasaki

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The first total synthesis of gymnocin-A (1), a cytotoxic polycyclic ether isolated from a notorious red tide dinoflagellate, Karenia mikimotoi, has been accomplished. The synthesis relies heavily on the Suzuki-Miyaura cross-coupling-based methodology to assemble the tetradecacyclic polyether skeleton. Convergent union of the GHI (5) and KLMN (6) rings, both of which were prepared from a common intermediate 7, and the subsequent ring closure of the J ring delivered the GHIJKLMN ring. The crucial coupling between the ABCD and FGHIJKLMN ring fragments (3 and 4, respectively) and stereoselective installation of the C17 hydroxyl group, followed by cyclization of the E ring gave rise to the tetradecacyclic polyether skeleton 2. Finally, incorporation of the 2-methyl-2-butenal side chain completed the total synthesis of gymnocin-A. The convergent nature of the synthesis, which employs three fragments of comparable complexity, is well-suited for preparation of various structural analogues of gymnocin-A to explore the structure-activity relationship. The results of preliminary structure-activity relationship studies of several synthetic analogues are also provided.

Original languageEnglish
Pages (from-to)4326-4335
Number of pages10
JournalJournal of the American Chemical Society
Volume127
Issue number12
DOIs
Publication statusPublished - Mar 30 2005

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Structure-Activity Relationship
Skeleton
Polyethers
Harmful Algal Bloom
Dinoflagellida
Cyclization
Hydroxyl Radical
Ether
Tides
Ethers
gymnocin A
2-methyl-2-butenal

All Science Journal Classification (ASJC) codes

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

Cite this

Convergent total synthesis of gymnocin-A and evaluation of synthetic analogues. / Tsukano, Chihiro; Ebine, Makoto; Sasaki, Makoto.

In: Journal of the American Chemical Society, Vol. 127, No. 12, 30.03.2005, p. 4326-4335.

Research output: Contribution to journalArticle

Tsukano, Chihiro ; Ebine, Makoto ; Sasaki, Makoto. / Convergent total synthesis of gymnocin-A and evaluation of synthetic analogues. In: Journal of the American Chemical Society. 2005 ; Vol. 127, No. 12. pp. 4326-4335.
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