4 、 有机磷类缩合剂 

       多种磷酸酯和磷酰胺类缩合剂也被广泛应用于酰胺的缩合。如二苯基磷酰氯（DPP-Cl）、氰代磷酸二乙酯（DECP）、叠氮化磷酸二苯酯（DPPA、硫代二甲基磷酰 基叠氮（MPTA）、 二（2-氧-3-唑烷基）磷酰氯（BOP-Cl）等。 

      在这些磷酸酯和磷酰胺类缩合剂中，DECP 常用于小量的多肽的合成， BOP-Cl特别适合与氨基酸的合成，其收率、消旋等都较好，但其缺点是，当胺的反应活性低时，常常得到酰化的唑烷。 

另外，BOP-Cl 的溶解性较差，导致反应时间较长，有时会长达四五天，常用 DMF 做反应溶剂。 

4.1 应用DPP-Cl为缩合剂合成酰胺示例 

以下反应用 DCC 只有 15%的收率, 但用 DPP-Cl 可以得到 94%收率。 

4.2 应用DPPA为缩合剂合成酰胺示例 

      To some of this free amine 30 (0.270 g, 0.96 mmol) was added DMF (5 mL), (2-phthalimidoethoxy)acetic acid 29 (0.237 g, 0.96 mmol), DPPA (0.25 mL, 1.15 mmol) and Et3N (0.29 mL, 2.11 mmol) at 0℃ while stirring.  The ice bath was removed after two hours and the reaction was stirred at R.T. overnight.  EtOAc (70 mL) was added and the solution was extracted successively with 10% citric acid, H2O, saturated NaHCO3 solution, H2O, and saturated NaCl solution (20 mL each), dried (anhydrous MgSO4) and finnaly evaporated in vacuo.  The oily residue was purified by column chromatography on silica gel, eluting with 7:1 CHCl3-MeOH to give the desired product 31 as a white solid. Yield: 81% (two steps); m.p.: 123-127 °C;  1H-NMR (DMSO-d6)  (ppm) = 1.10 　 -1.25 (m, 3H, CH3), 1.65-1.95 (m, 2H, CH2-　-Glu-NH2), 2.23-2.40 (m,  2H,  CH2-　-iGln), 3.44-3.60 (m, 6H, 2OCH3), 3.68 (t, J=6 Hz, CH2O), 3.80 (t, J=6 Hz, NCH2), 4.08-4.25 (m, 2H, 2CH), 4.64-4.90 (m, 1H, PNH), 7.05 (s, 1H, CONH2), 7.35 (s, 1H, CONH2), 7.40-7.60 (m, 1H, NH), 7.80-7.88 (m, 4H, phthaloyl). 

4.3 应用BOP-Cl为缩合剂合成酰胺示例

     To a solution of the acid 33 in dry CH2Cl2 (5 ml / mmol) was added diisopropyl ethylamine (DIEA, 1 equiv) under nitrogen, and the mixture was stirred for 10 min.  Then, BOP-Cl (1 equiv), amine 32 (1.1 equiv) and again DIPEA (2 equiv) were added.  After it was stirred overnight, most of the DCM was removed under reduced pressure and ethyl acetate (100 ml) was added.  The solution was washed three times with 5% NaHCO3 solution and once consecutively with water, 2M HCl solution, water and saturated brine (50 ml each).  The organic layer was dried over Na2SO4, and the solvent was evaporated to give the desired amide 34.