Synthesis and Biological Evaluation of QRSTUVWXYZA′ Domains of Maitotoxin

DOI HANDLE Web Site PubMed 被引用文献8件 参考文献70件 オープンアクセス
  • K. C. Nicolaou
    Department of Chemistry, BioScience Research Collaborative, Rice University, 6100 Main Street, Houston, Texas 77005, United States
  • Philipp Heretsch
    Department of Chemistry, BioScience Research Collaborative, Rice University, 6100 Main Street, Houston, Texas 77005, United States
  • Tsuyoshi Nakamura
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
  • Anna Rudo
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
  • Michio Murata
    Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan
  • Keiichi Konoki
    Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
  • BioScience Research Collaborative

この論文をさがす

説明

The synthesis of QRSTUVWXYZA' domains 7, 8, and 9 of the highly potent marine neurotoxin maitotoxin (1), the largest secondary metabolite isolated to date, is described. The devised synthetic strategy entailed a cascade Takai-Utimoto ester olefination/ring closing metathesis to construct ring Y, a hydroxydithioketal cyclization/methylation sequence to cast ring X, a Horner-Wadsworth-Emmons coupling of WXYZA' ketophosphonate 11 with QRSTU aldehyde 12 to form enone 10, and a reductive hydroxyketone ring closure to forge ring V. 2D NMR spectroscopic analysis and comparison of (13)C chemical shifts with those of the corresponding carbons of maitotoxin revealed close similarities supporting the originally assigned structure of this region of the natural product. Biological evaluations of various synthesized domains of maitotoxin in this and previous studies from these laboratories led to fragment structure-activity relationships regarding their ability to inhibit maitotoxin-elicited Ca(2+) influx in rat C6 glioma cells.

収録刊行物

被引用文献 (8)*注記

もっと見る

参考文献 (70)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ