发布时间 : 星期六 文章氨基的保护及脱保护更新完毕开始阅读f72c97b71611cc7931b765ce0508763230127459
dried with MgSO4, and evaporated to afford compound 2 (0.23 g, 84%) as an oily residue. 3.5.1.3
Teoc-OBt引入三甲基硅乙氧羰基(Teoc)示例
Boger, Dale L; Kim, Seng Heon et al., J. Am. Chem. Soc., 2001, 123(9), 1862-1871; Boger, Dale L; Kim, Seng Heon et al., J. Am. Chem. Soc., 2000, 122(30), 7416-7417
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%).
2.5.1.4一般氨基的三甲基硅乙氧羰基（Teoc）的引入示例
Mueller, Paul; Imogai, Hassan; Tetrahedron: Asymmetry, 1998, 9(24), 4419-4428 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. 2.5.2三甲基硅乙氧羰基（Teoc）的脱去
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。
2.5.2.1三甲基硅乙氧羰基（Teoc）的脱去示例
Gugiu, Bogdan G; Salomon, Robert G; Org. Lett., 2003, 5(16), 2797-2800 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).
2.6 甲（或乙）氧羰基
甲（或乙）氧羰基同前面提到的各种烷氧羰基不同，它对一般的酸、碱和氢解等都很稳定，在它的存在下，Cbz、Boc和苄基等可选择性去保护。 2.6.1 甲（或乙）氧羰基的引入
同Cbz、Fmoc 和Alloc的引入方法类似，用甲（或乙）氧羰酰氯在有机溶剂/Na2CO3、NaHCO3或有机碱同氨基化合物反应则可得到甲（或乙）氧羰基保护的氨基衍生物[1]。 1. E. J. Corey, M. G. Bock et al., Tetrahedron Lett. 1978, 1051 2.6.1.1 甲（或乙）氧羰基的引入示例
E. F. B. Mara; S. B. Hugo et al., Synthesis, 1999, 6, 943
To a suspension of 2b (5 mmol, 1.05 g) in acetone (10 mL) cooled to 0 °C (ice-salt bath) was added TEA (9.56 mmol, 1.74 mL). The mixture was stirred at r.t. for 15 min. To this mixture at 0 °C was added dropwise ethyl chloroformate (12.9 mmol, 1.16 mL). The solution was stirred at r.t. for 2 h and the solvent was removed in vacuo. The residue was treated with H2O (25mL) and then with HCl 10% until pH 3 and extracted with EtOAc. The organic layer was washed with H2O, dried (Na2SO4) and the solvent was removed in vacuo yielded 4b (76%) as thick oil. 2.6.1.2
甲（或乙）氧羰基的引入示例
M. Dawei; D. Ke et al., Tetrahedron: Asymmetry, 2002, 13, 961
A suspension of compound 1 (20 g, 77.8 mmol), NaHCO3 (13.0 g, 155.6 mmol) in water (120 mL) and chloroform (20 mL) was treated with methyl chloroformate (12.0 mL, 155.6 mmol) in a dropwise manner. The solution was stirred for 24
h and 1N aq. HCl was added to adjust the pH to 4. The mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried over MgSO4, and concentrated to yield compound 2 (23.3 g, 94%) as a crude solid. 2.5.2 甲（或乙）氧羰基的脱去
因为甲（或乙）氧羰基较强的稳定性，它们通常只用较剧烈的条件去保护，如HBr/HOAc处理[1]、KOH/MeOH、6 N HCl 和TMSI等。
1. M. C. Wani, H. F. Campbell et al., J. Am. Chem. Soc., 1972, 94, 3631; P. Magnus, J. Rodrigues-Lopez et al., J. Am. Chem. Soc., 1992, 114, 382; J. Patjens; G. T. Ramin et al., Helv. Chim. Acta. 1986, 69(4), 905-607 2.6.2.1 HBr-AcOH脱除甲（或乙）氧羰基示例
J. Patjens; G. T. Ramin et al., Helv. Chim. Acta. 1986, 69(4), 905-607 Compound 1 (18.1 g, 0.1 mol) was added to 33 % HBr (in AcOH, 100 mL, 0.52 mol) at room temperature. The mixture was stirred and heated to 70℃for 12 h. The excess HBr and AcOH were removed in vacuo. The residue was washed with dry ether (3 x 50 ml) to give compound 2 (23 g, 85 %) as a orange solid 2.6.2.2 KOH-MeOH脱除甲（或乙）氧羰基示例
A. R. Hergueta; C. Lopez et al., Tetrahedron: Asymmetry, 2003, 23, 3773 A mixture of compound 1(3.60 g, 14.0 mmol) and 5N KOH (25 mL) in MeOH (50 mL) was refluxed for 18 h and brought to pH 3 with 2N H2SO4. Removal of the solvents at low pressure afforded a white solid (10 g) that was extracted with MeOH, the extract was passed through basic ion exchange resin (Amberlite IRA-400(OH), 100 mL), and the eluate was concentrated under reduced pressure to a brown oil (2.81 g) that upon flash chromatography (1:1 EtOAc/MeOH) afforded a colourless oil that 1H NMR spectroscopy showed to be virtually pure compound 2 (1.87 g, 85%). [α]D25 = +22.6 (c=0.52, MeOH). 2.6.2.3 6NHCl脱除甲（或乙）氧羰基示例
F. Liu; Z. Huiyan et al., J. Org. Chem., 2003, 17, 6679
Compound 1 (44 mg, 0.14 mmol) was refluxed with HCl (6 N, 10 mL) for 4 days. The mixture was concentrated in vacuo to give compound 2 as a white solid (38
mg, 100%). [α] D = +33.2 (c =1.20, H2O). 2.6.2.3 TMSI脱除甲（或乙）氧羰基示例
G. M. Ksander; J. Reynalda de et al., J. Med. Chem., 2001, 26, 4677 A mixture of 8aR (1.53 g, 3.27 mmol), 75 mL of acetonitrile, and trimethylsilyliodide (1.86 mL, 13 mmol) was stirred overnight at room temperature. Methanol was added, and the mixture was concentrated, cold 1 N NaOH added, and the mixture was extracted with EtOAc. The organic layer was washed with aqueous Na2S2O3 and brine, dried, filtered, concentrated and recrystallized from ether to give 1.19 g (89%) of 9aR as a white solid melting at 109-112 °C.
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