P-59 Tubulysin類の全合成(ポスター発表の部)

• 澁江 卓

  杏林製薬探索研

• 岡本 巌

  昭和薬大

• 森田 延嘉

  昭和薬大

• 田村 修

  昭和薬大

書誌事項

タイトル別名

• Total Synthesis of Tubulysins

抄録

The tubulysind (1a-d), tetrapeptide derivatives, were first isolated from the myxobacterial strains Archangium gephyra and Angiococous disciformis. They are composed of four amino acid fragments, N-methyl-D-pipecolic acid (D-Mep), L-isoleucine (L-Ile), tubuvaline (Tuv), and tubuphenylalanine (Tup) / tubutyrosine (Tut)(Fig. 1), and exhibit strong antitumor activity by inhibiting tubulin polymerization. Owing to the remarkable biological activity and existence of unusual amino acids such as Tuv and Tup, tubulysins have attracted considerable attention as synthetic target molecules as well as leads for the development of new anticancer agents. We have now developed an efficient method for the stereoselective synthesis of Tuv-Me (2-Me) featuring the 1,3-dipolar cycloaddition of a nitrone D-3 with alkene 6 (Table 1 and Scheme 4), as well as a method for stereoselective synthesis of Tup (17-HCl) using na aldol reaction of 12 with aldehyde 13 followed by the Barton deoxygenation (Scheme 5). Using these methodologies, we have accomplished an efficient total synthesis of tubulysin U (1c) and V (1d), in which isoxazoline ring played an important role as a protecting group for the amine and the hydroxyl groups (Scheme 6). We have also synthesized tubulysin D (1b) and ent-tubulysin D (ent-1b) from 2-Me and 17-HCl, and ent-2-Me and ent-17-HCl by employing Ellman's sequence (Scheme 7). Antiproliferative activities of the synthetic tubulysins 1b, ent-1b, 1c, and 1d were evaluated in cancer cell lines.

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 51 (0), 413-418, 2009

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390001206077977216
• NII論文ID: 110009757677
• DOI: 10.24496/tennenyuki.51.0_413
• 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