hexanes) gave compound 2 (289 mg, 54%).
2.1.2.6 PdCl2催化氢解脱除带卤原子分子上的Cbz示例
To a solution o compound 1 (900 mg) in methylene chloride (16.5 ml) was addede PdCl2 (30 mg) and triethylamine (0.229 ml). Triethyl silane was added (2 x 0.395 ml) over 2 h. The reaction mixture stirred 1 h and 2 ml of trifluoroacetic acid was added. After 30 min the reaction was basified with 2 N NaOH, extracted with methylene chloride, dried over MgSO4, filtered and concentrated. Chromatography was run on a biotage 40S column with 3-5% MeOH/CH2Cl2 with 0.5% NH4OH to provide compound 2 as a oil (501 mg, 74%). 2.1.2.7 Pd黑催化氢解，用氨为溶剂,半胱氨酸的Cbz脱除示例
Arthur M. Felix, Manuel H. Jimenz et a1., Org. Syn., 59, 159
A dry 1-L three-necked, round-bottomed flask is equipped with a dry ice reflux condenser, a gas-inlet tube, and a magnetic stirring bar as illustrated in the figure. The reaction vessel is immersed in an acetone–dry ice bath, and a total of 300 mL of ammonia is passed through a drying tower containing potassium hydroxide pellets and collected in the flask. The bath is removed to permit the reaction to proceed at the boiling point of ammonia (33℃), and a gentle stream of dry nitrogen is bubbled into the flask. A solution of 0.708 g (0.80250 mole) of N-benzyloxycarbonyl-L-methionine in 10 ml. of N,N-dimethylacetamide 1.02 g (1.40 ml., 0.0101 mole) of triethylamine and 1.25 g of freshly prepared palladium black are added. The nitrogen stream is discontinued and replaced by a stream of hydrogen that has been passed through a concentrated sulfuric acid scrubber. The mixture is stirred under reflux for 5.5 hours to effect hydrogenolysis. The hydrogen stream is discontinued, a flow of nitrogen is resumed, and the dry ice is removed from the reflux condenser, permitting rapid evaporation of ammonia. The flask is attached to a rotary evaporator, and the mixture is evaporated to dryness under reduced pressure. The residue is dissolved in water and filtered through a sintered funnel of medium porosity to remove the catalyst. The filtrate is evaporated to dryness, and the residue
(354 mg, 95%) is crystallized from water–ethanol. The white crystalline product, after drying under reduced pressure at 25°, weighs 272–305 mg. (73–82%), m.p. 280–282° (dec.), [α]25D +23.1° (c = 1, aqueous 5 N hydrochloric acid).
酸解脱除 氨基甲酸苄酯在强酸性条件下容易去保护。HBr/HOAc 是酸解脱除苄氧羰基的最常用的试剂[1]。脱除反应主要按下式进行[2]。反应需要消耗2分子的HBr，Cbz的脱除速度随HBr浓度的增大而增大，因此实际上都是采用高浓度的过量HBr/HOAc溶液（1.2M-3.3M）以保证反应的完全。
1. D. Ben-Ishai, A. Berger., J. Org. Chem., 1952, 17, 1564; R. A. Boissonnas, J. Blodinger, A. D. Welcher., J. Am. Chem. Soc., 1952, 74, 5309
2. R. A. Boissonnas, J. Blodinger, A. D. Welcher., J. Am. Chem. Soc., 1952,
74, 5309; J. Meienhofer, E. Schnabel., Z. Naturforsch., 1965, 20b, 661 含有丝氨酸[1]和苏氨酸[2]的肽或其它含羟基的氨基衍生物用HBr/HOAc脱除Cbz时会发生羟基的O-乙酰化反应。虽然O-乙酰基能用碱皂化或氨解脱去，但为了避免这个副反应，可以改用HBr/二氧六环或HBr/三氟乙酸来代替HBr/HOAc[3]。由于HBr在三氟乙酸中的溶解度较小，因此不能预先制成HBr/三氟乙酸溶液，而只能将保护的肽或氨基衍生物溶于无水三氟乙酸中，先于0℃下通入干燥的HBr，待Cbz大部分脱除后，再室温通短时间以求完全脱除变化基。Cbz被HBr分解产生的溴化苄能同肽中的某种氨基酸反应，也是需要加以注意的。如，甲硫氨酸的硫原子能同溴化苄反应生成S-苄基甲硫氨酸[4]，防止的办法是加入硫醚（CH3SC2H5）为捕捉剂[5]。色氨酸被HBr/HOAc分解产生有色物质，防止的办法是加入亚磷酸二乙酯。硝基精氨酸会发生硝基的部分脱落，改用液体HBr于-67℃处理可以避免。
1. G. D. Fasman, E. R. Blout., J. Am. Chem. Soc., 1960, 82, 2262
2. S. Fujiwara, S. Moerinaga, K. Narita., Bull. Chem. Soc. Japan., 1962, 35, 438
3. J. Meienhofer, E. Schnabel., Z. Naturforsch., 1965, 20b, 661; 黄惟德等，
生物化学与生物物理学报, 1961, 98
4. N. F. Albertson, F. C. Mckay., J. Am. Chem. Soc., 1953, 73, 5323 5. S. Guttmann, R. A. Boissonnas, Helv. Chim. Acta., 1959, 42, 1257
用液体HF在0℃处理10-30分钟即可将Cbz完全脱去。FSO3H、CH3SO3H
[1][2][2, 3]
、
CF3SO3H[3, 4]和C6H5SCH3-TFA[5]也是较好的试剂。Me3SiI在氯仿、乙腈中能于几分钟内选择性脱去Cbz和Boc保护基[6]。对于BBr3/CH2Cl2而言，较大分子的肽的Cbz衍生物可在TFA中去除，因为肽在酸中的溶解度比在CH2Cl2中大[7]。从肽中脱去Cbz，可在TFA中添加0.5 M 4-（甲硫基）苯酚[8]或使用HF/Me2S/对甲苯酚[9]（25:65:10,v/v）来抑制Bn+对芳香氨基酸的加成。
1. S. Sakakibara et a1., Bull. Chem. Soc. Japan., 1967, 40, 2164; S. Matsuura, C. H. Niu, J. S. Cohen., J. Chem. Soc. Chem. Commun., 1976, 451
2. H. Yajima, H. Ogawa, H. Sakurai., J. Chem. Soc. Chem. Commun., 1977, 909 3. H. Yajima et a1., J. Chem. Soc. Chem. Commun., 1974, 107 4. H. Yajima et a1., Chem. Pharm. Bull., 1975, 23, 1164
5. Y. Kiso, K. Ukawa, T. Akita., J. Chem. Soc. Chem. Commun., 1980, 101 6. R. S.Lott, V. S. Chauham, C. H. Stammer., J. Chem. Soc. Chem. Commun., 1979, 495
7. J. Pless, W. Bauer., Angew Chem., Int. Ed. Engl., 1973, 12, 147; A. M. Felix.,
J. Org. Chem., 1974, 39, 1427
8. M. Bodanszky, A. Bodanszky., Int. J. Pept. Protein Res., 1984, 23, 287 9. J. P. Tam, W. F. Heath, R. B. Merrifield., J. Am. Chem. Soc., 1983, 105, 6442
此外，已经报道过的还有以下的一些不常用的方法。如HCl/CHCl3[1]、HCl/HOAc[2]、HBr/SO2[3]、液体HBr[4]、TosOH[5]、HI/HOAc[6]、碘化磷[7]、Et3SiH[8]、沸腾的TFA[9]、8M HCl的乙醇液或6 M HCl回流1小时[10]或浓盐酸于25-75℃加热处理1-1.5小时[11]等。 1. G. D. Fasman, M. Idelson, E. R. Blout., J. Am. Chem. Soc., 1961, 83, 709 2. R. B. Merrifield., J. Am. Chem. Soc., 1963, 85, 2149 3. M. Idelson, E. R. Blout., J. Am. Chem. Soc., 1958, 80, 4631 4. M. Brenner, H. C. Curtius., Helv. Chim. Acta., 1963, 46, 2126 5. E. Taschner, B. Liberek, Abstr. Int. Cong. Biochemistry, Vienna 1958 6. E. Waldschmidt-Leitz, K. Kuhn., Chem. Ber., 1951, 84, 381
7. E. Brand, B. F. Erlanger, H. Sachs., J. Am. Chem. Soc., 1952, 74, 1849
8. Birkofer et al., Angew. Chem., Int. Ed., 1965, 4, 417 9. F. Weygand, W. Steglich., Z. Naturforsch., 1959, 14b, 472
10. A.E. Barkdoll, W. F. Ross., J. Am. Chem. Soc., 1944, 66, 567; G. Chelucci, M. Falorni, G. Giacomelli., Synthesis., 1990, 1121 11. J. White., J. Biol. Chem., 1934, 106, 141 2.1.2.8 HBr-AcOH脱除Cbz示例
B. Anna; P. Gerald., Heterocycles, 2002, 58, 521
A solution of the amine Cbz compund (208 mg, 0.44 mmol) in 33 % hydrobromic acid in acetic acid (1 mL) and glacial acetic acid (0.6 mL) was stirred at rt for 3 h under an atmosphere of nitrogen. The volatiles were removed in vacuo to leave the free amine hydrobromide (168 mg, 91 %) as a brown, highly hygroscopic powder; [α]D =-18.0° (c = 0.4, EtOH); 2.1.2.9 TMSI脱除Cbz示例1
Me3SiI (0.73 ml, 0.73 mmol) was added to a soluton of compound 1 (146 mg, 0.33 mmol) in acetonitrile (10 ml) at room temperature, and the resulting mixture was stirred at room temperature for 2 h. Et3N (0.12 ml) was added and the mixture was stirred at room temperature for 15 min. The solvents were removed in vacuo, and the residue was extracted with ethyl acetate. The combined organics were washed with sodium bicarbonate and brine, dried over sodium sulfate and filtered. Solvents were removed and the residue was used directly in the next step. 2.1 g (4.45 mmol) of compound 1 in 30 ml of CH2Cl2 were combined with 1.9 ml (13.4 mmol) Me3SiI and stirred for 16 h at room temperature. Then 20 ml of MeOH were addede, the mixture was stirred for a further 30 min at room temperature and the reaction mixture was evaporated down completely. The residue was purified by chromatography on silica gel (eluding gradient: CH2Cl2/(MeOH/conc. Ammonia 95:5) = 70/30 – 60/40) to yield compound 2 (690 mg, 56%).