Total syntheses of chaetocin and ent-chaetocin

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• 作者：Eriko Iwasa^a ; ^b ; Yoshitaka Hamashima^a ; ^† ; ; Shinya Fujishiro^a ; ^c ; Daisuke Hashizume^a ; Mikiko Sodeoka^a ; ^b ; ^{sodeoka@riken.jp"" rel=""nofollow}
• 关键词：Total synthesis ; Chaetocin ; ent-Chaetocin ; Histone methyltransferase inhibitor ; Radical coupling
• 刊名：Tetrahedron
• 出版年：2011
• 出版时间：2 September 2011
• 年：2011
• 卷：67
• 期：35
• 页码：6587-6599
• 全文大小：2120 K

文摘

The first total synthesis of chaetocin (1), a potent histone methyltransferase inhibitor, is described in detail. Key reactions were radical bromination for α-oxidation of the diketopiperazine ring, and reductive radical coupling for construction of the dimeric core structure. Stereoselective construction of the disulfide bridges was achieved via substitution reaction with H₂S. The total synthesis of 1 was accomplished in nine steps starting from known d-amino acid derivatives. Total synthesis of non-natural ent-chaetocin (ent-1) was also achieved via the established synthetic route, starting from l-amino acid derivatives.