Epimerization of peptide nucleic acids analogs during solid-phase synthesis: optimization of the coupling conditions for increasing the optical purity
作者:Roberto Corradini、Stefano Sforza、Arnaldo Dossena、Gerardo Palla、Raniero Rocchi、Ferdinando Filira、Flavia Nastri、Rosangela Marchelli
DOI:10.1039/b104146k
日期:2001.10.11
2 and 3 was carried out either in solution, or by solid-phase peptide synthesis (SPPS) on an MBHA-Rink amide resin. The oligomers turned out to contain large amounts of epimerization products, especially those obtained by SPPS. Therefore, we examined carefully the parameters which may be involved in epimerization: the nature of the coupling reagent, of the base, and the addition mode. Coupling of the
肽核酸 (PNA)类似物基于 Ñ α - (胸腺嘧啶-1-基乙酰)鸟氨酸以前显示与互补RNA形成三链体。为了获得用于杂交实验的光学纯化合物,请使用基于D-或左旋鸟氨酸,Ñ δ -Fmoc- ñ α - (胸腺嘧啶-1-基乙酰)鸟氨酸2和Ñ δ -Fmoc- ñ α - (尿嘧啶-1-基乙酰)鸟氨酸3是由一个单步或通过简单的三中合成从开始步骤过程ñ δ -保护鸟氨酸; 后一种方法得到对映体纯产物。2和3的低聚反应可以在溶液中进行,也可以通过固相进行肽 MBHA-Rink上的合成(SPPS) 酰胺树脂。证明低聚物包含大量差向异构产物,尤其是通过SPPS获得的差向异构产物。因此,我们仔细检查了差向异构化可能涉及的参数:偶联剂的性质,碱基的性质和添加方式。单体L - 3的偶联在各种条件下进行。当使用(7-氮杂苯并三唑-1-基)-1,1,3,3-四甲基铀六氟磷酸盐(HATU)作为偶联剂和2,4,6-三甲基吡啶