对甲苯磺酰基（Tos） 

     对甲苯磺酰胺由胺和对甲苯磺酰氯在吡啶或水溶性碱存在下制得的，它是稳定的氨基保护基之一，对碱性水解和催化还原稳定。碱性较弱的胺如吡咯和吲哚形成的对甲苯磺酰胺比碱性更强的烷基胺所形成的对甲苯磺酰胺更易去保护，可以通过碱性水解去保护，而后者通过碱性水解去保护是不可能的。对甲苯磺酰胺一个很有吸引力的性质是 这些衍生物的酰胺或氨基甲酸酯更容易形成结晶。除在早期作过α-氨基的保护基外， 一般都是用作碱性氨基酸的侧链保护基。 

     Tos-氨基酸能够通过酰氯、叠氮、DCC 和四乙基焦亚磷酸等方法进行接肽，但混合 酸酐法一般不能采用。这是因为 Tos 基得强烈吸电子效应使得被酰化的氨基上的氢原子 容易离去，而在用混合酸酐法接肽时会产生 N，N-双取代等副反应使产率很低。同样， Tos-氨基酸的酰氯在 NaOH 等强碱作用下很不稳定，会发生分解生成 Tos-NH2、醛和 CO （见下式）

1 、对甲苯磺酰基的引入 

      对甲苯磺酰氯在 NaOH、NaHCO3 或其他有机碱存在下同氨基酸、吡咯和吲哚等反 应很容易得到良好产率的 Tos-衍生物。 

对甲苯磺酰基的引入示例 

   22.9 g (90 mmol) of compound 1 , 13.66 g (135 mmol) of triethylamine, and 100 mL of dry THF are placed in a 300-mL, round-bottomed flask, equipped with a pressure-equalizing dropping funnel, a magnetic stirring bar, and a nitrogen inlet. The dropping funnel is charged with a solution of 18.9 g (99.1 mmol) of p-toluenesulfonyl chloride in 50 mL dry THF. The reaction mixture is cooled to 0°C with magnetic stirring, and the solution of p-toluenesulfonyl chloride is delivered dropwise over a 30-min period. The resulting cloudy solution is stirred for 60 hr at ambient temperature. After this time period, the reaction mixture is diluted with 50 mL of saturated sodium chloride solution and 50 mL of ethyl acetate, transferred to a 500-mL separatory funnel, mixed thoroughly, and the organic phase separated. The aqueous phase is extracted twice with 50 mL of ethyl acetate. The combined organic layers are dried (Na2SO4), filtered, concentrated under reduced pressure, and the resulting residue purified by chromatography to give 22.43 g (61%) of compound 2 (Rf = 0.34, CHCl3/EtOAc, 1:1) as a colorless solid, mp 144–146°C. 

2 、对甲苯磺酰基的脱去 

     Tos 非常稳定，它经得起一般酸解(TFA 和 HCl 等）、皂化、催化氢解等多种条件得 处理比受影响，常用萘钠[1]、Na/NH3(液) [ 2] 和 Li/NH3(液) [ 3]处理脱去。HBr/苯酚[4]和 Mg/MeOH 也是比较好的去保护方法[5]。值得注意的是，Na/NH3(液)的操作比较麻烦， 并且会引起一些肽键的断裂和肽链的破坏。另外，有时 HF/MeCN 回流也能脱去 Tos 基 。

 Na/NH3脱除对甲苯磺酰基示例 

     To a two necked flask equipped with a dry ice condenser was added compound 1 (3.20 g, 10.1 mmol) in THF (15 ml) and ammonia gas to condense about 25 ml of liquid. Small pieces of sodium (552 mg, 24.2 mmol) were added to the stirred solution until a blue color color persisted for 5 min. After stirring for 10 min, the reaction was quenched by adding dropwise glacial acetic acid (2 ml). The NH3 was allowed to evaporate. The crude product was dried in vacuo for 1 h to give compound 2 (1.3 g, 89%) as a colorless oil. 

    Lithium metal was added to a solution of compound 1 (1.5 g, 5.01 mmol) in 5 ml of THF and 200 ml of liquid NH3. The resulting dark blue solution was stirred for 1 h and then quenched with 1 ml of absolute ethanol. The ammonia was evaporated. The residue was diluted with saturated aqueous NaCl (30 ml), and extracted with CH2Cl2 (4 x 20 ml). The combined layers was dried and the solvent evaporated to give compound 2 (0.4 g, 55%) as oil. 

 Na/萘脱除对甲苯磺酰基示例 

    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. 

HBr/苯酚脱除对甲苯磺酰基示例 

     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. 

Mg/MeOH 脱除对甲苯磺酰基示例 

    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.