烯丙氧羰基(Alloc)保護(hù)氨基

烯丙氧羰基（Alloc）同前面提到的Cbz、Boc和Fmoc不同，它對(duì)酸、堿等都很穩(wěn)定，在它的存在下，Cbz、Boc和Fmoc等可選擇性去保護(hù)，而它的脫去則通常在Pd(0)的存在下進(jìn)行。

烯丙氧羰基（Alloc）的引入

Alloc-Cl在有機(jī)溶劑/Na2CO3、NaHCO3溶液或吡啶中同氨基化合物反應(yīng)則可得到Aloc保護(hù)的氨基衍生物【 E. J. Corey, J. W. Suggs., J. Org. Chem., 1973,38, 3223】

反應(yīng)實(shí)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）的脫去

Alloc保護(hù)基對(duì)酸、堿等較強(qiáng)的穩(wěn)定性，它們通常只用Pd(0)，如Pd(PPh3)4或Pd(PPh3)2Cl2存在的條件去保護(hù)。例如，Alloc衍生物用Pd(PPh3)4/Me2NTMS處理，可以得到易水解的氨基甲酸TMS酯 [TetrahedronLett., 1992, 33,477]。脫去含硫衍生物中的Alloc 時(shí)，如蛋氨酸，Pd(PPh3)4/二甲基環(huán)己二酮/TH則不會(huì)被毒化[Angew.Chem. Int. Ed. Engl., 1984, 23, 436]。如果在酸性條件下脫除Alloc，則最好采用Pd(PPh3)2Cl2/Bu3SnH/p-NO2C6H4OH/CH2Cl2[TetrahedronLett., 1982, 23,1825]。在異戊烯酯或肉桂酸酯存在下，可用Pd(OAc)2/TPPT/CH3CN/Et3N/H2O去保護(hù)，但隨時(shí)間的增加，這些酯也會(huì)反應(yīng)，并且氨基甲酸異戊烯酯和烯丙基碳酸酯同樣被斷裂[TetrahedronLett., 1997, 38,2955]。當(dāng)加入Boc2O、AcCl、TsCl、或丁二酸酐時(shí)，Pd(PPh3)2Cl2/Bu3SnH可將Alloc基轉(zhuǎn)變?yōu)槠渌陌费苌铩Ａ硗猓珹lloc也可在Pd(PPh3)4/HCOOH/TEA[J.Med. Chem., 1992, 35, 2781]或AcOH/NMO催化脫去[J.Org. Chem., 1996, 61, 3983]。

去保護(hù)機(jī)理參考

反應(yīng)實(shí)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 give113 (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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