三甲基硅乙氧羰基(Teoc)同常用的Cbz、Boc, Fmoc 和Alloc不同，它对大部分酸碱，及贵金属催化等都很稳定，氨基在其保护下，Cbz、Boc，Fmoc和Alloc等可选择性去保护，而它的脱保护需要氟负离子。常用托保护试剂有TBAF【 Bioorg. Med. Chem. Lett., 2004, 14(22), 5569-5572; Eur. J. Org. Chem., 2003, 17, 3288-3299; J. Am. Chem. Soc., 2001, 123(9), 1862-1871】、TEAF和HF【Tetrahedron Lett., 1986, 27(38), 4541-4544】等。另外，TFA也可选择性去保护三甲基硅乙氧羰基【J. Org. Chem., 2001, 66(21), 7223-7226】。
上保护：
利用Teoc-Cl、Teoc-OSu或Teoc-OBt等试剂，在碱存在下同胺反应则可得到Teoc保护的氨基衍生物。
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NaHCO3(3.78 g, 45 mmol) and compound 1(15 mmol) are added to water (15 ml) and the mixture is stirred at room temperature for 30 min or until the majority of the solids dissolve. To this suspension is added a solution of Teoc-Cl in dioxane (30 ml). The resultant mixture is stirred vigorously at room temperature overnight, poured into water (50 ml) and extracted with ether (3 x 50 ml), the organic extracts being discarded. The aqueous layer is acidified to Ph = 2 with saturated potassium hydrogen sulfate solution and extracted with ether (3 x 50 ml). The combined organic extracts are washed with water (3 x 75 ml), dried with MgSO4, and evaporated to give compound 2【Synthesis, 1987, 4, 346-349】To compound 1 (486 mg, 8.5 mmol) in CH2Cl2 (15 mL) was added, at −10°C, diisopropylethylamine (1.72 g, 17 mmol) followed by Teoc-Cl (3.06 g, 17 mmol) in CH2Cl2, and finally, dimethylaminopyridine (DMAP, 30 mg). The mixture was stirred overnight, then hydrolyzed with satd NaHCO3, and extracted with CH2Cl2 (3 x 30 mL) at 0°C and satd Na2CO3. After drying and evaporation of the solvent, the crude product was purified by chromatography (SiO2; hexane:AcOEt = 85:5) and afforded compound 2 (1.49 g, 88%) as a colorless liquid.【Tetrahedron: Asymmetry, 1998, 9(24), 4419-4428】
To a stirred suspension of compound 1 (0.13 g, 1 mmol) in water (1 ml) is added a solution of triethylamine (0.26 g, 2.6 mmol) in dioxane (1 ml). To the resultant solution is added solid Teoc-OSu (0.29 g, 1.1 mmol). The mixture is stirred at room temperature overnight, then diluted with water (5 ml), acidified with saturated potassium hydrogen sulfate solution, and extracted with ether (3 x 15 ml). The combined organic layers are washed with water (4 x 20 ml), dried with MgSO4, and evaporated to afford compound 2 (0.23 g, 84%) as an oily residue.【Synthesis, 1987, 4, 346-349】![]()
To a stirred suspension of compound 1 (0.24 g, 1 mmol) in water (1 ml) is added a solution of triethylamine (0.26 g, 2.6 mmol) in dioxane (1 ml) followed by solid Teoc-Bt (0.31 g, 1.1 mmol). The mixture is stirred at room temperature overnight, then diluted with water (5 ml), acidified with saturated potassium hydrogen sulfate solution, and extracted with ether (3 x 15 ml). The combined organic layers are washed with water (4 x 20 ml), dried with MgSO4, and evaporated to afford compound 2 (0.36 g, 92%).【J. Am. Chem. Soc., 2001, 123, 1862-1871】
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【Organic Letters, 2007, 9，5231 - 5234】
脱保护：
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一般三甲基硅乙氧羰基(Teoc)脱除主要通过TBAF(四丁基氟化胺)，TEAF (四乙基氟化胺)或TMAF(四甲基氟化胺)来脱除，在脱除过程中，TBAF将产生四丁基胺盐的副产物，常常不易除去，而且它的质谱丰度高，往往影响产品的交货，此时可用TMAF或TEAF来代替。【氟离子对Si-O键和Si-C键的断裂】
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Compound 1 (33 mg, 0.042 mmol) was dissolved in THF and TBAF (0.070 mL 1M in THF containing 18.4 mg, 0.070 mmol) was added, and the solution stirred at room temperature for 48 h under argon following the disappearance of compound 1 by TLC (36 h). After the removal of solvent by rotary evaporation under low pressure the product was purified by flash chromatography using CHCl3/MeOH/H2O (60:38:2) to give compound 2 (20 mg, 72%) with Rf = 0.53 in CHCl3/MeOH/H2O (60:38:2)【Org. Lett., 2003, 5, 2797-2800】
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