Antineoplastic Agents. 590. X-ray Crystal Structure of Dolastatin 16 and Syntheses of the Dolamethylleuine and Dolaphenvaline Units

Three advances necessary to bring dolastatin 16 (1) into full-scale preclinical development as an anticancer drug have been accomplished. The X-ray crystal structure of dolastatin 16 has been solved, which allowed stereoselective syntheses of its two new amino acid units, dolamethylleuine (Dml) and dolaphenvaline (Dpv), to be completed. The X-ray crystal structures of synthetic Z-Dml and TFA-Dpv have also been completed.

为将海兔毒素16（dolastatin 16，化合物1）开发为抗癌药物并推进至全规模临床前研发，现已完成三项必要进展。海兔毒素16的X射线晶体结构已成功解析，这使得其两种新型氨基酸单元——多甲基亮氨酸（dolamethylleuine，Dml）与多苯缬氨酸（dolaphenvaline，Dpv）——的立体选择性合成得以完成。合成Z-Dml与TFA-Dpv的X射线晶体结构也已解析完成。