School of Natural and Computing Sciences, University of Aberdeen, Meston Building, Aberdeen, AB24 3UE.
J Org Chem. 2010 Feb 5;75(3):564-9. doi: 10.1021/jo902116p.
A rapid repetitive solution-phase synthesis of peptides is described. The procedure involves coupling of amino acids and peptide acids, instead of the usual amino esters and peptide esters, to slight excesses of pentafluorophenyl active esters in a THF/water solvent mixture. Due to their poor solubility, peptide acid intermediates are easily isolated in high purity by acidification under controlled conditions and removal of excess active esters by selective extraction. Contrary to modern repetitive solution-phase peptide synthesis procedures, our approach does not require time-consuming neutralization reactions and reduces significantly the number of operation units that are necessary to obtain peptide intermediates. Efficiency of the method was demonstrated by the rapid synthesis of short hydrophobic and hydrophilic peptides, the antimalarial cycloheptapeptide mahafacyclin B, and a protected form of the hydrophilic pentapeptide GRGDS.
描述了一种快速重复的溶液相肽合成方法。该方法涉及将氨基酸和肽酸与五氟苯基活泼酯在 THF/水溶剂混合物中以略微过量偶联，而不是通常的氨基酯和肽酯。由于其溶解度差，肽酸中间体在受控条件下酸化并通过选择性萃取除去过量的活泼酯，很容易以高纯度分离。与现代重复溶液相肽合成方法相反，我们的方法不需要耗时的中和反应，并大大减少了获得肽中间体所需的操作单元的数量。该方法的效率通过快速合成短疏水性和亲水性肽、抗疟环庚七肽马法西克林 B 以及亲水性五肽 GRGDS 的保护形式得到了证明。
