School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
Chemistry. 2010 Mar 1;16(9):2758-63. doi: 10.1002/chem.200902766.
A series of benzo-macrolactones has been prepared by chemical synthesis, and evaluated as inhibitors of heat shock protein 90 (Hsp90), an emerging attractive target for novel cancer therapeutic agents. A new synthesis of these resorcylic acid macrolactone analogues of the natural product radicicol is described in which the key steps are the acylation and ring opening of a homophthalic anhydride to give an isocoumarin, followed by a ring-closing metathesis to form the macrocycle. The methodology has been extended to a novel series of macrolactones incorporating a 1,2,3-triazole ring.
已通过化学合成制备了一系列苯并大环内酯，并将其评估为热休克蛋白 90（Hsp90）的抑制剂，Hsp90 是新型癌症治疗药物的新兴有吸引力的靶标。本文描述了天然产物雷地昔醇的这类重排树脂酸大环内酯类似物的新合成方法，其中关键步骤是均苯四甲酸酐的酰化和开环反应生成异香豆素，然后进行闭环复分解反应形成大环。该方法已扩展到包含 1,2,3-三唑环的新型大环内酯系列。
