A practical synthesis of Nα-Fmoc protected L-threo-β-hydroxyaspartic acid derivatives for coupling via α- or β-carboxylic group
A practical synthesis of Nα-Fmoc protected L-threo-β-hydroxyaspartic acid derivatives for coupling via α- or β-carboxylic group
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DOI：
10.1007/s00726-010-0806-x
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发表时间：
2012-01-01
期刊：
影响因子：
3.5
通讯作者：
Cudic, Predrag
中科院分区：
文献类型：
--
作者：
Bionda, Nina;Cudic, Mare;Cudic, Predrag
本文报道了一种简单实用的与Fmoc固相肽合成方法完全兼容的正交保护tHyAsp衍生物的通用合成方案。我们的方法包括通过与l-Lys共结晶对市售的d，l-tHyAsp外消旋混合物进行对映分辨，然后通过离子交换色谱得到对映纯的l-tHyAsp和d- thyasp，并对它们进行选择性正交保护。通过这种方法，N (α) - fmoc保护的tHyAsp衍生物可以通过α -或β -羧基偶联到树脂或生长的肽链上。此外，通过β -羧基将tHyAsp偶联到氨基树脂上，可以制备含有tHyAsn序列的肽，进一步提高了所制备的tHyAsp衍生物的合成效用。
A simple and practical general synthetic protocol towards orthogonally protected tHyAsp derivatives fully compatible with Fmoc solid-phase peptide synthetic methodology is reported. Our approach includes enantioresolution of commercially available d,l-tHyAsp racemic mixture by co-crystallization with l-Lys, followed by ion exchange chromatography yielding enantiomerically pure l-tHyAsp and d-tHyAsp, and their selective orthogonal protection. In this way N (alpha) -Fmoc protected tHyAsp derivatives were prepared ready for couplings via either alpha- or beta-carboxylic group onto the resins or the growing peptide chain. In addition, coupling of tHyAsp via beta-carboxylic group onto amino resins allows preparation of peptides containing tHyAsn sequences, further increasing the synthetic utility of prepared tHyAsp derivatives.