渝偲医药关于：三苯甲基保护的胺基的脱保护介绍

Trt容易用酸脱去，如用HOAc或50%（或75%）HOAc的水溶液在30℃或回流数分钟顺利除去。这时N-Boc和O-But可以稳定不动。其他如HCl/MeOH、HCl/CHCl3、HBr/HOAc和TFA都能很方便的脱去Trt，用HCl/MeOH处理Trt-Lys(Trt)OCH3可以得到Lys(Trt)OCH3，说明侧链上的Trt比α-Trt 对酸更稳定一些。Cys(Trt)、His(Trt)和Try(Trt)等的侧链上的N-Trt比Nα-Trt 对酸稳定，因此可以采用适当的酸解条件选择性脱去Nα-Trt而保留侧链上的N-Trt。

Trt对酸的敏感程度还随所用的酸的不同而异，例如Trt对醋酸比较敏感，在80%的醋酸中，Trt的脱除速度大约比Bpoc快7倍，比Boc快21，000倍，因而可以在Boc或Moz存在下选择性地脱去Trt。但如用0.1MHBr/HOAc为试剂，Trt脱去速度反而慢于Boc和Moz。

Trt也能被催化氢解脱去，但脱去速度比O-苄基和N-Cbz要慢得多。根据所用试剂和脱去方法得不同，Trt被分解所形成的产物也不同（见下式）。

一、TFA脱去三苯甲基示例

M. Firouz Mohd Mustapa,RichardHarris,Nives Bulic-Subanovic et al., J. Org. Chem., 2003,21, 8185; S. Vinay, M. Mizio etal., Tetrahedron, 2002, 44, 9101

Compound 1(3.5 g, 4.6 mmol) was treated with a 5%solution of trifluoroacetic acid (1.4 mL, 18 mmol, 4 equiv) in CHCl3(27 mL) under inert conditions for 4 h. The resultingsolution was diluted with CHCl3(200 mL) andwashed with sodium hydrogen carbonate (5% aq w/v, 2 × 75 mL) and water (2 × 50mL). The solvent was removed in vacuo. The material was then redissolved in CHCl3(20 mL) and MeOH (20 mL), and the solvents were againremoved in vacuo to yield compound 2(2.1 g, 87%) as a pale yellowliquid.

二、 TFA-TIS脱去三苯甲基示例

Swall, Vinay; Matteuccl et al., Tetrahedron, 2002, 58(44), 9101-9110

Compound 1(2.0 g, 2.71 mmol) was stirred with TFA(4.9mL), CH2Cl2 (4.9mL) and TIS (0.2 mL) for 1 h. Solventwas removed in vacuo and the residue purified by column chromatography (SiO2, MeOH/CHCl3, 1:9 v:v) toafford compound 2(1.16 g,91%) as a white solid.

三、TFA-Et3SiH脱去三苯甲基示例

Pickersgill, I.Fraser; Rapoport, Henry; J. Org. Chem., 2000,65(13),4048-4057

To a stirred solution of compound 1(3.34 g, 3.82 mmol) and triethylsilane (0.64 mL, 4.01mmol) in CH2Cl2(16 mL) cooled to 0 °C was added dropwise TFA (16 mL). Theresultant colorless solution was allowed to warm to rt, with stirring continuedfor 1 h. The solvents were evaporated, the residue was triturated with hexanes(5 x 50 mL), the hexane extracts were discarded, and the oily residue waspartitioned between CHCl3/IPA (250 mL, 3/1) and 1 M NaOH (precooled to 0 °C,100 mL). The aqueous phase was extracted with further portions of CHCl3/IPA (2 x 200mL, 3/1), and the combined organic phase was dried, filtered, and evaporated togive compound 2(2.04 g, 100% crude yield) as a pale yellowoil.

4.1.2.4 HOAc脱去三苯甲基示例

Vago, Istvan; Kalaus, Groergy et al., Heterocycles,2001, 55(5), 873-880

0.85 g(2 mmol) of compound 1 wasdissolved in the mixture of 20 mL of acetic acid and 0.5 mL of water. The solutionwas heated under argon at 60 ºC for 1 h, and then allowed to cool to rt. Theresulted dark solution was diluted with 200 mL of water; the triphenylmethanolwas removed by extraction with ether. The pH of the watery phase was adjustedto a value of 8 with sodium carbonate solution, extracted with dichloromethane;the extract was dried with magnesium sulfate, evaporated to dryness in vacuumtogive, compound 2(0.24 g,64 %) as unstable brown oil.

4.1.2.5 TBS和Boc官能团存在下用BF3-HOAc脱去三苯甲基示例

Pickersgill, I, Fraser; Rapoport, Henry; J. Org. Chem., 2000, 65(14),4048-4057

To a solution of 32 (2.67 g, 3.98 mmol) in CH2Cl2(27 mL) cooled to 0 °C were added glacial acetic acid (6.7 mL)and BF3.Et2O (0.529 mL, 4.17 mmol) dropwise, and the mixture wasstirred at 0 °C for 2 h.Cold (0 °C) 1 M NaOH (160 mL) was added and the mixturepartioned between CHCl3/IPA (320 mL, 3/1) and cold (0 °C) 1 M NaOH (66 mL), followed by extraction with further portions ofCHCl3/IPA (2 x 160 mL, 3/1). The combined organic phase wasdried, filtered, and evaporated to a residue which was chromatographed (CH2Cl2/MeOH,19/1 to 9/1) to give 33 (1.50 g,88%) as a colorless oil: [α]22D= +3.1 (c = 1.0,CHCl3).

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