烯丙氧羰基(Alloc)保护氨基

烯丙氧羰基（Alloc）同前面提到的Cbz、Boc和Fmoc不同，它对酸、碱等都很稳定，在它的存在下，Cbz、Boc和Fmoc等可选择性去保护，而它的脱去则通常在Pd(0)的存在下进行。

烯丙氧羰基（Alloc）的引入

Alloc-Cl在有机溶剂/Na2CO3、NaHCO3溶液或吡啶中同氨基化合物反应则可得到Aloc保护的氨基衍生物【 E. J. Corey, J. W. Suggs., J. Org. Chem., 1973,38, 3223】

反应实例

To a stirred solution of compound 1 (3.0 g, 15.86 mmol) in a mixture of aq. NaHCO3andTHF (8/2, 20 mL) was added allylchloro formate (2.54 mL, 23.81 mmol), dropwiseand at 0 °C. Themixture was stirred at room temperature for 12 h and then diluted with ethylacetate and washed 3 N HCl, dried and the solvent removed in vacuo togive compound 2 as a pale yellow oil, which was used without further purification(3.55 g, 82%).

【Micale, Nicola;Vairagounder, Rajendran et al J. Med. Chem., 2004, 47(26),6455-6458】

To a solution of 17 (1.0 g, 1.97 mmol) in EtOAc (10 ml) was added 4 M HCl/EtOAc (20 mL), and the mixture was stirredfor 6 h at room temperature. After evaporation, to the suspension of theresidue in CH2Cl2(40 mL) were added triethylamine (2.75 mL,19.7 mmol) and allyl chloroformate (0.627 mL, 5.91 mmol) at -10°C.The reaction mixture was poured into H2O and the whole was extracted withEtOAc. The organic layer was washed with brine, dried over MgSO4, andevaporated under reduced pressure. The residue was purified by silica gelcolumn chromatography (EtOAc/acetone = 8:1) to give 18 (863 mg, 92.1%)as a foam. [ a]D25=19.6 (c =1.0,CHCl3).

【H. Imamura; A.Shimizu et al., Tetrahedron, 2000, 56(39), 7705】

烯丙氧羰基（Alloc）的脱去

Alloc保护基对酸、碱等较强的稳定性，它们通常只用Pd(0)，如Pd(PPh3)4或Pd(PPh3)2Cl2存在的条件去保护。例如，Alloc衍生物用Pd(PPh3)4/Me2NTMS处理，可以得到易水解的氨基甲酸TMS酯 [TetrahedronLett., 1992, 33,477]。脱去含硫衍生物中的Alloc 时，如蛋氨酸，Pd(PPh3)4/二甲基环己二酮/TH则不会被毒化[Angew.Chem. Int. Ed. Engl., 1984, 23, 436]。如果在酸性条件下脱除Alloc，则最好采用Pd(PPh3)2Cl2/Bu3SnH/p-NO2C6H4OH/CH2Cl2[TetrahedronLett., 1982, 23,1825]。在异戊烯酯或肉桂酸酯存在下，可用Pd(OAc)2/TPPT/CH3CN/Et3N/H2O去保护，但随时间的增加，这些酯也会反应，并且氨基甲酸异戊烯酯和烯丙基碳酸酯同样被断裂[TetrahedronLett., 1997, 38,2955]。当加入Boc2O、AcCl、TsCl、或丁二酸酐时，Pd(PPh3)2Cl2/Bu3SnH可将Alloc基转变为其它的胺衍生物。另外，Alloc也可在Pd(PPh3)4/HCOOH/TEA[J.Med. Chem., 1992, 35, 2781]或AcOH/NMO催化脱去[J.Org. Chem., 1996, 61, 3983]。

反应实例

To a solution of the Allocprotected ester (140.7 mg, 0.2.23mmol)and 1,3-dimethylbarbituric acid (228 mg, 1.46 mmol) in THF (15 mL) was addedtetrakis(triphenylphosphine)palladium (43.9 mg, 0.0379mmol,17 mol%), and the resulting mixture was stirred at rt for 27 h. The mixture wasthen poured into saturated aq. NaHCO3and extracted fourtimes with Et2O. The combined extract was dried (MgSO4)and concentrated in vacuo. The residue was purifiedby chromatography (CHCl3/MeOH, 20 : 1 to 2 : 1) to give the corresponding freeamino ester as a colorless oil (79.5 mg, 65%).

【Y. Matsushima;H. Itoh etal., J. Chem. Soc. Perkin Trans. 1., 2004, 7,949】

To asolution of 112 (0.97 g,1.4 mmol) in CH2Cl2 (19 mL) were added dimethylamino- trimethylsilane(1.32 mL, 8.4 mol) and trimethylsilyl trifluoroacetate (1.45 mL, 8.4 mmol). Thesolution was stirred at 20 °Cfor 10 min, and then Pd(PPh3)4(97 mg, 0.084mmol) was added and stirring was continued for 2.5 h. The mixture wasevaporated and the residual oil was dissolved in EtOAc (50 mL). The solutionwas washed with 10% aq NaHCO3and brine,dried, and evaporated. The residue was chromatographed (SiO2; EtOAc/hexane 1:2)to give 113 (0.67 g, 78%):foam; TLC Rf) 0.27 (EtOAc).

【P. Angehrm; S.Buchmann et al., J. Med. Chem., 1992, 47(6), 1487】

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