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 compound 1 (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 compound 2 as a white solid, which was recrystallized from Et2O (1.2 g, 92% yield): mp 197~198°C.
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