不用酸堿，TBAF就可以脫保護的氨基保護基團----三甲基硅乙氧羰基（Teoc）

三甲基硅乙氧羰基(Teoc)同常用的Cbz、Boc, Fmoc 和Alloc不同，它對大部分酸堿，及貴金屬催化等都很穩定，氨基在其保護下，Cbz、Boc，Fmoc和Alloc等可選擇性去保護，而它的脫保護需要氟負離子。常用托保護試劑有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也可選擇性去保護三甲基硅乙氧羰基【J. Org. Chem., 2001, 66(21), 7223-7226】。

上保護：

利用Teoc-Cl、Teoc-OSu或Teoc-OBt等試劑，在堿存在下同胺反應則可得到Teoc保護的氨基衍生物。

NaHCO 3 (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 MgSO 4 , and evaporated to give compound 2

【 Synthesis , 1987 , 4 , 346-349 】

To compound 1 (486 mg, 8.5 mmol) in CH 2 Cl 2 (15 mL) was added, at ?10°C, diisopropylethylamine (1.72 g, 17 mmol) followed by T eoc -Cl (3.06 g, 17 mmol) in CH 2 Cl 2 , and finally, dimethylaminopyridine (DMAP, 30 mg). The mixture was stirred overnight, then hydrolyzed with satd NaHCO 3 , and extracted with CH 2 Cl 2 (3 x 30 mL) at 0°C and satd Na 2 CO 3 . After drying and evaporation of the solvent, the crude product was purified by chromatography (SiO 2 ; 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 MgSO 4 , 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 MgSO 4 , and evaporated to afford compound 2 (0.36 g, 92%).

【J. Am. Chem. Soc., 2001, 123, 1862-1871】

【Organic Letters, 2007, 9，5231 - 5234】

脫保護：

一般三甲基硅乙氧羰基(Teoc)脫除主要通過TBAF(四丁基氟化胺)，TEAF (四乙基氟化胺)或TMAF(四甲基氟化胺)來脫除，在脫除過程中，TBAF將產生四丁基胺鹽的副產物，常常不易除去，而且它的質譜豐度高，往往影響產品的交貨，此時可用TMAF或TEAF來代替。【】

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 CHCl 3 /MeOH/H 2 O (60:38:2) to give compound 2 ( 20 mg , 72%) with R f = 0.53 in CHCl 3 /MeOH/H 2 O (60:38:2)

【Org. Lett., 2003, 5, 2797-2800】

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