氨基的保护及脱保护

Kaiser, Alexander; Balbi, Miriam et al., Tetrahedron: Asymmetry, 1999, 10(5), 1001-1014

To a solution of compound 1 (0.78 g, 1.83 mmol) in dry THF (20 ml) a solution of sodium naphthalenide [31 ml; prepared by stirring naphthalene (3.96 g, 31.2 mmol) and small pieces of sodium (1.92 g, 83.8 mmol) in dry THF (120 ml) for 3 h at room temperature under nitrogen] was added over 10 min at -78°C. After 6.5 h at -78°C, water (5 ml) was added, and THF was removed under reduced pressure. The mixture was diluted with water (10 ml) and extracted with EtOAc (3 x 30 ml). The combined EtOAc layers were washed with brine (2 x 20 ml), dried and evaporated. Column chromatography (CH2Cl2: MeOH, 9:1) afforded compound 2 (0.17 g, 39%) as a colorless oil. 3.1.2.4

HBr/苯酚脱除对甲苯磺酰基示例

Calvisi, Giuseppina; Dell-Uomo, Natalina et al., Eur. J. Org. Chem., 2003, 23,

4501-4506

A round-bottom flask containing a mixture of compound 1 (600 mg, 1.94 mmol), phenol (547 mg, 5.82 mmol) and HBr (7.5 mL, 48%) was placed in an oil bath previously heated to 130 °C and refluxed for 18 hours. The reaction mixture was then allowed to cool to room temperature, diluted with water and extracted twice with EtOAc. The aqueous layer was evaporated under vacuum, the residue was taken up several times with CH3CN (evaporating under vacuum every time) until a solid residue, insoluble in CH3CN, was obtained. The solid was filtered and dried to give compound 2 (230 mg, 95%) as the dihydrobromide salt.

3.1.2.5 Mg/MeOH脱除对甲苯磺酰基示例

Nenajdenko, Valentine G; Karpov, Alexei S et al., Tetrahedron: Asymmetry, 2001, 12(18), 2517-2528

To a suspension of Mg (0.45 g, 20 mmol) in MeOH (5 mL) was added a solution of compound 1 (0.74 g, 2 mmol) in MeOH (10 mL). The resulting suspension was sonicated for 1 h until consumption of the starting material was complete. The reaction mixture was then diluted with aqueous NH4Cl and extracted with ether (3 x 5 mL). The organic layer was dried over MgSO4 and evaporated. To resulting oil ethanolic solution HCl (2 M, 0.5 mL) was added. Hydrochloride was precipitated, filtered and washed with ether to afford compound 2 HCl salt (0.46 g, 90%) as a white solid.

3.3 三氟乙酰基（Tfa）

三氟乙酰基（Tfa）是Weygand最先引入到多肽合成中的[1]。三氟乙酰基（Tfa）可用三氟醋酐导入，在稀碱液中很容易脱去。Tfa保护的氨基酸或多肽在高真空下易于气化，因而能用于气相层析以检测消旋的程度[2]和测定天然肽的排列顺序[3]，而且由于含有F，也可用F NMR来检测合成肽的纯度、消旋程度以及类似物的鉴定等。由于N-Tfa-氨基酸在接肽时易于消旋，也是采用此保护基时应该注意的地方。 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 3.3.1 三氟乙酰基的引入

由于三氟醋酐同氨基酸反应时易生成恶唑烷酮而发生消旋[1]，因此，同甲酰基的引入一样，在低温下于三氟醋酸溶液中用三氟醋酐酰化为好[2]。一般而言，CF3COOEt/Et3N/MeOH是较好的方法[3]，可在仲胺存在下，选择性地保护伯胺[4]。并且该方法地聚合物方法也已得到发展[5]。在TFAA/18-crown-6/Et3N中，伯胺与18-crown-6形成络合物，可选择性地酰化仲胺[6]。而在仲胺存在下，CF3COO-邻苯二甲酰亚胺也可选择性地将TFA基团引入到伯胺[7]。

1. F. Weygand, E. Leising., Chem. Ber., 1954, 87, 248

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