Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin

Hisaaki Onoue, Riho Marubayashi, Erina Ishikawa, Keiichi Konoki, Kohei Torikai, Makoto Ebine, Michio Murata, Tohru Oishi

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3 Citations (Scopus)

Abstract

Structure-activity relationship studies of maitotoxin (MTX), a marine natural product produced by an epiphytic dinoflagellate, were conducted using chemically synthesized model compounds corresponding to the partial structures of MTX. Both enantiomers of the LMNO ring system were synthesized via aldol reaction of the LM ring aldehyde and the NO ring ketone. These fragments were derived from a common cis-fused pyranopyran intermediate prepared through a sequence involving Nozaki-Hiyama-Kishi reaction, intramolecular oxa-Michael addition, and Pummerer rearrangement. The NOPQR(S) ring system, in which the original seven-membered S ring was substituted with a six-membered ring, was also synthesized through the coupling of the QR(S) ring alkyne and the NO ring aldehyde and the construction of the P ring via 1,4-reduction, dehydration, and hydroboration. The inhibitory activities of the synthetic specimens against MTX-induced Ca2+ influx were evaluated. The LMNO ring system and its enantiomer induced 36 and 18% inhibition, respectively, at 300 μM, whereas the NOPQR(S) ring system elicited no inhibitory activity.

Original languageEnglish
Pages (from-to)9595-9618
Number of pages24
JournalJournal of Organic Chemistry
Volume82
Issue number18
DOIs
Publication statusPublished - 2017 Jan 1

ASJC Scopus subject areas

  • Organic Chemistry

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    Onoue, H., Marubayashi, R., Ishikawa, E., Konoki, K., Torikai, K., Ebine, M., Murata, M., & Oishi, T. (2017). Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin. Journal of Organic Chemistry, 82(18), 9595-9618. https://doi.org/10.1021/acs.joc.7b01658