76-05-1 / 三氟乙酰基（Tfa）的引入

由于卤原子具有较高的电负性，随着乙酰基结构中卤原子的增多，酰基碳的电子云密度减小，亲电性增加，更容易脱除。三氟乙酰基是其中性能最好的保护基，它是Weygand最先引入到多肽合成中的[1]。三氟乙酰基（Tfa）可用三氟乙酸酐导入，在稀碱液中很容易脱去。不仅用于肽的合成，也可以用于甾体上的氨基和糖上氨基的保护。如分子中同时存在伯胺和仲胺，则三氟乙酸乙酯可以优先与伯胺反应。与乙酸酐一样，三氟乙酸酐在18-冠-6存在下，可以选择性的酰化仲胺。与此相反，三氟乙酸-丁二酰亚胺可选择性的酰化伯胺，而仲胺不受影响。三氟乙酰基在碱性，如0.2M NaOH，1M Piperidine， K2CO3/MeOH/H2O 或NaBH4/EtOH条件下脱除时，Boc，Cbz，Trt，Alloc，Fmoc等氨基保护基不受影响。Tfa保护的氨基酸或多肽在高真空下更易于气化，因而能用于气相层析以检测消旋程度[2]和测定天然肽的排列顺序[3]，而且由于含有F，也可用19F NMR来检测合成肽的纯度、消旋程度以及类似物的鉴定等[4]。

1. F. Weygand, E. Csendes.,Angew.Chem.,1952,64,136

2. F. Weygand, D.Hoffmann, A. Prox.,Z.Naturforsch.,1968,23b, 279

3. N. Ikekawa.,J. Biochem.,1963,54, 279

4.E. Bayer et al.,J. Am.Chem. Soc.,1972,94, 265

氨基化合物TFAA引入Tfa保护基

To a stirred suspension of the hydrobromide salt of compound1(1.3 g, 3.6 mmol) and 4-N,N- (dimethylamino) pyridine(0.04 g, 0.3 mmol) in CH2Cl2(40 mL) was added Et3N(16.0 mL, 12.0 mmol), and the mixture was cooled to 0°C. Trifluoroacetic anhydride (2.5 mL, 17 mmol) was then added to the reaction dropwise. The mixture was allowed to warm to room temperature and stirred for 8 h. The mixture was then diluted with CH2Cl2(50 mL) and washed with 2 N HCl (50 mL), saturated NaHCO3(50 mL), and brine (50 mL).The organic phase was then dried (MgSO4), filtered, and evaporated to leave compound2as a white solid, which was recrystallized from Et2O (1.2 g, 92% yield): mp 197~198°C.

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