17 神経保護作用物質セロフェンド酸の合成(口頭発表の部)

• 久米 利明

  京大院薬

• 赤池 昭紀

  京大院薬

• 寺内 太朗

  エーザイ

• 世永 雅弘

  エーザイ

• 杉本 八郎

  京大院薬:エーザイ

• 豊田 真弘

  東北大院薬

• 和田 俊博

  東北大院薬

• 横田 正宏

  東北大院薬

• 松浦 公紀

  東北大院薬

• 浅野 武司

  東北大院薬

• 井原 正隆

  東北大院薬

書誌事項

タイトル別名

• 17 Synthesis of Neuroprotective Substances, Serofendic Acids

抄録

Serofendic acids A and B, possessing atisane skeleton, isolated from fetal calf serum (FCS) show potent protective action against neurotoxicity induced by glutamete and an No donor. Due to its scarce availability from nature, the development of efficient synthesis is highly demanded. Eisai group synthesized serofendic acids from (-)-isosteviol through methyl atisienoate and established its absolute configuration including the stereochemistry about sulfoxide. Tohoku group studied four approaches for the synthesis of atisane derivatives. The first approach using intramolecular Diels-Alder reaction resulted in a non stereoselective production of atisane skeleton. The second approach utilizing intramolecular double Michael reaction provided the required atisane derivative in a highly stereoselective manner. However, the transformation of the product into natural diterpenes required a number of steps for the removal of ester group and introduction of C_1, unit. In order to prepare a bicyclo[2.2.2]octane ring system carrying exo olefin part, cyclization of vinyl radical was next examined. Although total synthesis of (±)-gumiferolic acid showing potent growth-regulatory activity was achieved by the third approach, the yield of the key step was low. Finally, the bicyclo[3.2.1]octane possessing exo olefin part and oxygen functionality was prepared by cycloalkenylation reaction using catalytic amount of palladium(II) acetate in DMSO under oxygen atmosphere and converted into methyl atisienoate via intramolecular Diels-Alder reaction and homoallyl-homoallyl radical rearrangement. Thus, (-)-enantiomer of atisane diterpene convertible to serofendic acids was effectively synthesized.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 45 (0), 97-102, 2003

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390001206079792768
• NII論文ID: 110006682276
• DOI: 10.24496/tennenyuki.45.0_97
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可