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

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)9595-9618
ページ数24
ジャーナルJournal of Organic Chemistry
82
発行部数18
DOI
出版物ステータス出版済み - 1 1 2017

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Bioactivity
Enantiomers
Aldehydes
Alkynes
Biological Products
Ketones
Dehydration
Thermodynamic properties
maitotoxin

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

これを引用

Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin. / Onoue, Hisaaki; Marubayashi, Riho; Ishikawa, Erina; Konoki, Keiichi; Torikai, Kohei; Ebine, Makoto; Murata, Michio; Oishi, Tohru.

:: Journal of Organic Chemistry, 巻 82, 番号 18, 01.01.2017, p. 9595-9618.

研究成果: ジャーナルへの寄稿記事

Onoue, Hisaaki ; Marubayashi, Riho ; Ishikawa, Erina ; Konoki, Keiichi ; Torikai, Kohei ; Ebine, Makoto ; Murata, Michio ; Oishi, Tohru. / Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin. :: Journal of Organic Chemistry. 2017 ; 巻 82, 番号 18. pp. 9595-9618.
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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.",
author = "Hisaaki Onoue and Riho Marubayashi and Erina Ishikawa and Keiichi Konoki and Kohei Torikai and Makoto Ebine and Michio Murata and Tohru Oishi",
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AU - Ishikawa, Erina

AU - Konoki, Keiichi

AU - Torikai, Kohei

AU - Ebine, Makoto

AU - Murata, Michio

AU - Oishi, Tohru

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AB - 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.

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