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目的制备用于全合成新型卡泊芬净类环六脂肽抗真菌剂的关键脂三肽片段(4″-烷氧基-1,1:′4,′1″-三联苯-4-甲酰)-三肽(1)。方法以L-脯氨酸甲酯(4)为原料,经与N-叔丁氧羰基-L-苏氨酸(a)或N-叔丁氧羰基-L-缬氨酸(b)缩合、脱叔丁氧羰基后与Nα-(9-芴甲氧羰基)-Nδ-叔丁氧羰基-L-鸟氨酸缩合、脱9-芴甲氧羰基后与4″-烷氧基-1,1:′4,′1″-三联苯-4-甲酸-N-羟基苯并三氮唑“活泼酯”(Ⅰc~Ⅰg)缩合5步反应制备目标脂三肽1。结果以65.2%~85.4%的总收率合成了10个脂三肽lac~1ag和1b c~1bg,其结构经电喷雾质谱(ESI-MS)和氢谱(1H-NMR)确证。结论该合成路线具有反应条件温和、操作简便、总收率高的优点。
OBJECTIVE: To prepare the key lipopeptide fragment (4 “-alkoxy-1,1: ’4’ ’’ ’’ ’- terphenyl-4- Acyl) -tripeptide (1). Methods L-Proline methyl ester (4) was used as a starting material and condensed with N-tert-butoxycarbonyl-L-threonine (a) or N- After removing tert-butoxycarbonyl, Nα- (9-fluorenylmethoxycarbonyl) -Nδ-tert-butoxycarbonyl-L-ornithine is condensed to give 9-fluorenylmethoxycarbonyl, which is condensed with 4 ”-alkoxy- The target lipopeptide 1 was prepared by condensation reaction of 4 ’, 1’ - terphenyl - 4 - carboxylic acid - N - hydroxybenzotriazole with “active ester” (Ⅰc ~ Ig) in 5 steps. Results Ten lipopeptides, lac ~ 1ag and 1b c ~ 1bg, were synthesized in a total yield of 65.2% ~ 85.4%. Their structures were confirmed by electrospray ionization mass spectrometry (ESI-MS) and 1H-NMR. Conclusion The synthetic route has the advantages of mild reaction conditions, easy operation and high total yield.