以N-丙酰基-(3R,4S)-3-甲基-4-苯基-2-羰基噁唑啉与N-(叔丁氧羰基)-S-脯氨醛为原料,经羟醛缩合反应合成了高立体专一性、具有三个手性中心的(4S,5S,2'R,3'R,2″S)-3-[3'-(N-叔丁氧羰基-2″-吡咯烷基)-3'-羟基-2'-甲基丙基)]-4-甲基-5-苯基-2-羰基噁唑烷酮(6);6脱去手性辅基,甲基化3'-羟基合成了抗肿瘤活性肽海兔毒素10的关键合成子——(2S,3S,2'S)-3-(N-叔丁氧羰基-2'-吡咯烷基)-3-甲氧基-2-甲酸丙酸,其结构经1H NMR,13C NMR,IR和MS表征。
(4S,5S,2′R,3′R,2″S)-3-[3′-(N-tert-butoxycarbonyl-2″-pyrrolidinyl)-3′-hydroxy-2′-methylpropanoyl)]-4-methyl-5-phenyl-2-oxazolidinone(6) with three chair center and high stereroslectively was prepared by aldol condensation of(4R,5S)-4-methyl-3-(1-oxopropyl)-5-phenyloxazolidin-2-one and(N-tert-butoxycarbonyl)-S-prolinal.A key synthon of Dolastatin 10,(2R,3R,2′S)-3-(N-tert-butoxycarbonyl-2′-pyrrolidinyl)-methoxyl-2-methylpropanonic acid(Dap),was synthesized by methylation of 3′-OH and dechiral agon in 6.The structures were characterized by 1H NMR,13C NMR,IR and MS.