Sivanandaiah K M, Babu V V, Shankaramma S C
Department of Studies in Chemistry, Central College, Bangalore University, Karnataka, India.
Int J Pept Protein Res. 1994 Jul;44(1):24-30. doi: 10.1111/j.1399-3011.1994.tb00400.x.
Coupling of Fmoc-amino acid chlorides can be mediated by the potassium salt of 1-hydroxybenzotriazole (KOBt), the reaction being carried out in an organic medium. The use of a base like NaHCO3/Na2CO3 or DIEA/NMM/pyridine is not necessary. Coupling is fast and racemization free; the work-up, isolation of the product and scale-up are easy. The pentapeptide sequence of Fmoc-[Leu]enkephalin was thus synthesized in the solution phase on a 5 mmol scale without isolation of any intermediate. Acylation of C-protected N-methylamino acid esters by Fmoc-N-methylamino acid chlorides by this procedure is also feasible, as demonstrated by the synthesis of cyclosporin A fragments 4-7 and 8-11. The peptides obtained in high yields were crystalline solids, unlike earlier reports in which they were obtained mostly as oily or foamy intermediates. They showed spectral properties identical with those of the authentic compounds.
芴甲氧羰基（Fmoc）-氨基酸氯化物的偶联反应可由1-羟基苯并三唑钾盐（KOBt）介导，反应在有机介质中进行。无需使用如碳酸氢钠/碳酸钠或二异丙基乙胺（DIEA）/N-甲基吗啡啉（NMM）/吡啶等碱。偶联反应快速且无消旋化；后处理、产物分离及放大操作都很容易。因此，芴甲氧羰基-[亮氨酸]脑啡肽的五肽序列在溶液相中以5 mmol规模合成，无需分离任何中间体。通过该方法，芴甲氧羰基-N-甲基氨基酸氯化物对C-保护的N-甲基氨基酸酯的酰化反应也是可行的，环孢素A片段4-7和8-11的合成证明了这一点。得到的肽以高收率获得，为结晶固体，这与早期报道不同，早期报道中它们大多作为油状或泡沫状中间体获得。它们显示出与真实化合物相同的光谱性质。
