1. Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin
- Author
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Kohei Torikai, Erina Ishikawa, Makoto Ebine, Keiichi Konoki, Hisaaki Onoue, Riho Marubayashi, Michio Murata, and Tohru Oishi
- Subjects
Stereochemistry ,Molecular Conformation ,Alkyne ,010402 general chemistry ,Ring (chemistry) ,Nitric Oxide ,01 natural sciences ,Aldehyde ,chemistry.chemical_compound ,Aldol reaction ,Animals ,Pyrans ,chemistry.chemical_classification ,Maitotoxin ,Aldehydes ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Pummerer rearrangement ,Organic Chemistry ,Oxocins ,Stereoisomerism ,Glioma ,P ring ,Ketones ,0104 chemical sciences ,Rats ,Hydroboration ,chemistry ,Calcium ,Marine Toxins - 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%...
- Published
- 2017