2．烷氧羰基类保护基
烷氧羰基类保护基可用于氨基酸，以在肽合成中减少外消旋化的程度。外消旋化发生在碱催化的N-保护的羧基活化的氨基酸的偶联反应中，也发生在易由N-酰基保护的氨基酸形成的中间体恶唑酮中。
要使外消旋化程度减到最小，需使用非极性溶剂、最弱的碱、低的反应温度，并使用烷氧羰基类保护的氨基酸是有效的。其中常用的有，易通过酸性水解去保护的Boc基、由催化氢解去保护的Cbz基、用碱经β-消除去保护的Fmoc基和易由钯催化异构化去保护的Alloc基。
2.1苄氧羰基（Cbz）
苄氧羰基（Cbz）是1932年Bergmann发现的一个很老的氨基保护基，但一直到今天还在应用。其优点在于：试剂的制备和保护基的导入都比较容易；N-苄氧羰基氨基酸和肽易于结晶而且比较稳定；苄氧羰基氨基酸在活化时不易消旋；能用多种温和的方法选择性地脱去。 2.1.1苄氧羰基的导入
苄氧羰基的导入，一般都是用Cbz-Cl。游离氨基在用NaOH 或NaHCO3 控制的碱性条件下可以很容易同Cbz-Cl反应得到N-苄氧羰基氨基化合物。α,β-二胺可用该试剂在pH= 3.5-4.5稍有选择性地被保护，其选择性随碳链地增长而减弱，如H2N(CH2)nNH2, n=2时71%被单保护; n=7时29%被单保护[1]。 氨基酸酯同Cbz-Cl的反应则是在有机溶剂中进行，并用碳酸氢盐或三乙胺来中和反应所产生的HCl。此外，Cbz-ONB（4-O2NC6H4OCOOBn）等苄氧羰基活化酯也可用来作为苄氧羰基的导入试剂，该试剂使伯胺比仲胺易被保护，但苯胺由于亲核性不足，与该试剂不反应[2]。
R1HNCbz-ClR2BaseR1R2NCbzNH2R2OOCR1Cbz-ClBaseR2OOCNHCbzR1
1．G. J. Atwell, W. A. Denny., Synthesis, 1984, 1032
2．D. R. Kelly, M. Gingell, Chem. Ind.(London), 1991, 888
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Cbz-Cl很容易用苯甲醇同光气的反应来制备（见下式），在低温下可以保存半年以上而不发生显著的分解。
CH2OHCOCl2CH2OCOCl+HCl
除Cbz-Leu为油状物外，绝大多数氨基酸的苄氧羰基衍生物都可以得到结晶。有的N-苄氧羰基氨基酸能同它的钠盐按一定比例形成共晶，共晶产物的熔点较高，并难溶于有机溶剂。例如，苯丙氨酸经苄氧羰基化后再加酸析出Cbz-Phe时往往得到共晶产物（熔点144℃），此共晶产物用乙酸乙酯和1M HCl一道震摇时可完全转化为Cbz-Phe而溶于乙酸乙酯中。因此。除Cbz-Gly以外，一般都是采用酸化后用有机溶剂提取的方法来得到纯的N-苄氧羰基氨基酸。
2.1.1.1 游离氨基酸的Cbz保护示例
Konda-Yamada, Yaeko; Okada, Chiharu et al., Tetrahedrom; 2002, 58(39), 7851-7865
Cbz-Cl (18.5 μl, 0.155 mmol) in diethyl ether (0.2 ml) was dropped to a solution of (R)-1 (36.4 mg, 0.129 mmol) in 10% aqueous Na2CO3 (1.8 ml) at 0°C, and stirred for 5 h. The reaction mixture was acidified with 10% citric acid, extracted with CHCl3 (10 mlX3). The organic layer was washed with water, dried over Na2SO4, evaporated to give light yellow gels, which were purified by preparative TLC (CHCl3/MeOH=5:1) to afford (R)-6 (25.7 mg, 47.1%) as yellow amorphous solid. Rf = 0.87 (n-BuOH/AcOH/H2O=4:1:5); [a]D23 = -27.270 (c = 0.99, CHCl3);
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2.1.1.2 氨基酸酯的Cbz保护示例
OSONH2.HCl1Cbz-ClK2CO3SOONHCbz2
M. Carrasco, R. J. Jones, S. Kamel et a1., Org. Syn., 70, 29
A 3-L, three-necked, Morton flask equipped with an efficient mechanical stirrer, thermometer, and a dropping funnel is charged with L-methionine methyl ester hydrochloride 1 (117.6 g, 0.56 mol), potassium bicarbonate (282.3 g, 2.82 mol, 5 eq.), water (750 mL), and ether(750 mL), and the solution is cooled to 0°C. Benzyl chloroformate (105 g, 88.6 mL, 0.62 mol, 1.1 eq.) is added dropwise over 1 hr, the cooling bath is removed, and the solution is stirred for 5 hr. Glycine (8.5 g, 0.11 mol, 0.2 eq.) is added (to scavenge excess chloroformate) and the solution is stirred for an additional 18 hr. The organic layer is separated, and the aqueous layer is extracted with ether (2 × 200 mL). The combined organic layers are washed with 0.01 M hydrochloric acid (2 × 500 mL), water (2 × 500 mL), and saturated brine (500 mL), and then dried (Na2SO4), filtered, and evaporated on a rotary evaporator. The resulting oil is further dried in a Kugelrohr oven (50°C, 0.1 mm, 12 hr) to leave product 2 as a clear oil that solidifies upon cooling: 165–166 g (98–99%), mp 42–43°C.
2.1.1.3 氨基醇的Cbz保护示例(1)
H2NOHCbz-ClNa2CO3THF, H2OCbzHNOH
Clariana, Jaume; Santiago, G. G. et al Tetrahedron: Asymmetry, 2000, 11(22), 4549-4558
Benzyl chloroformate (0.95 ml, 6.7 mmol) was added via syringe into a stirred mixture of aminoalcohol 7 (0.989 g, 5.1 mmol) and sodium carbonate (0.683 g, 6.4 mmol) in the solvent system water (10 ml)–THF (3 ml) maintained at 0°C. The mixture was stirred at room temperature for 18 h (TLC monitoring) and then partitioned between dichloromethane and
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water. The organic phase was dried and evaporated to afford a white solid which was passed through a column of silica gel with hexanes–ethyl acetate (v:v 2:1) to afford the desired product (1.198 g, 72%), mp 125–127°C.
2.1.1.4氨基醇的Cbz保护示例(2)
OHCbz-ClH2NOOK2CO3Tol, H2OCbzHNOOOH
Inaba, Takashi; Yamada, Yasuki et al J. Org. Chem., 2000, 65(6), 1623-1628
To a mixture of toluene (3.85 L), water (3.85 L), and K2CO3 (470 g, 3.40 mol) were successively added 1a (770 g, 2.72 mol) and CbzCl (488 g, 2.72 mol) with vigorous stirring at a temperature below 25 °C. After stirring at room temperature for 3 h, triethylamine (27.5 g, 270 mmol) and NaCl (578 g) were successively added, and the mixture was stirred for a further 30 min. The organic layer was separated and concentrated to give the desired product as oil, which was used for the next reaction without purification. The analytical sample was prepared by column chromatography;
2.1.2苄氧羰基的脱去
苄氧羰基的脱除主要有以下几种方法：1). 催化氢解；2). 酸解裂解；3). Na/NH3（液）还原。 一般而言目前实验室常用简洁的方法就是催化氢解， 但当分子中存在对催化氢解敏感或钝化的基团时，我们就必须采用化学方法如酸解裂解或Na/NH3（液）还原等。
催化氢解如下式所示。催化氢解的供氢体可以是H2、环己二烯[1, 2]、1，4-环己二烯
[2]
、甲酸铵[3]和甲酸[4-6]等，以后四个为供氢体的反应又叫催化转氢反应，通常这比催化
氢化反应更迅速。
R2R1NCbzH2CH3R2+R1NCOOHCH3+CO2+R1HNR2
催化剂主要用5-10%的钯-碳、10-20%的氢氧化钯-碳或钯-聚乙烯亚胺，钯-聚乙烯亚
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