設計與合成 1,2-取代 4-Benzylidene-5-imidazolinone 衍生物作為 GFP Chromophore 類似物
Abstract
本論文主旨為 GFP chromophore 類似物的合成研究。利用 N-acylglycine 為起始物，在醋酸酐 / 醋酸鈉的條件下與各種具取代基的苯甲醛進行合環反應形成 4-benzylidene-5-oxazolinone的衍生物。我們先利用一級胺類或 C-端具保護基的胺基酸於室溫下對oxazolinone 進行開環，形成含有 2-acylamido-3-arylacrylamide 的直鏈開環結構，再利用本論文的條件，以 pyridine 為溶劑和反應試劑，對其進行合環反應，有效率的形成一系列 4-benzylidene-5-imidazolinone的衍生物，之後並藉由方法學來測試此合環條件的普遍應用性。當使用不同的 N-acylglycines, 一級胺與各種苯環對位具取代基的苯甲醛，可以合成一系列的 1,2-位取代 4-benzylidene-5-imidazolinones 的衍生物作為 GFP chromophore 的類似物，包含了 1 位接有 CH3, Bn, CH2COOMe, CH2COOH, CH3CHCOOH, CH3CHCOOMe, H 的官能基；2 位接有 CH3, 2-phthalimidopropyl 的官能基；benzylidene對位上接有 H, halide, CN, OH 等的官能基。結果顯示，我們發展的方法經由開環再合環的路徑形成 4-benzylidene-5-imidazolinones，相較於之前文獻報導過的方法，更有效率且溫和。
The main focus of this thesis is to study the synthesis of GFP chromophore analogs via a cyclization reaction. N-acylglycines were heated with various benzaldehydes and sodium acetate in acetic anhydride to form a series of 4-benzylidene-5-oxazolinone derivatives. The oxazolinones were treated with primary amines or C-terminal protected amino acids under room temperature to afford the ring-opened adducts, which contained the 2-acylamido-3-arylacrylamide moiety. Our investigation has found that the desired 4-benzylidene-5-imidazolinone derivatives could be obtained in good yields when the ring-opened adducts were heated in pyridine. We have also demonstrated the generality of the methodology. When different N-acylglycines and primary amines were employed, a wide variety of 1- and 2-substituted 4-benzylidene-5-imidazolinones could be obtained. It is also applicable to various para-substituted benzaldehydes that would afford different substituents at the para-position of the benzylidene. We have successfully synthesized a series of 1,2-substituted-4-benzylidene-5-imidazolinone as the analogs of GFP chromophores, comprising CH3, Bn, CH2COOMe, CH2COOH, CH3CHCOOH, CH3CHCOOMe, H at 1-position; CH3, Ph, 2-phthalimidopropyl at 2-position; H, halide, CN, OH at the para-position of benzylidene. Our results have shown that our approach toward the 4-benzylidene-5-imidazolinones from ring-opening / ring-closing route is more facile and efficient than the existing methods.
The main focus of this thesis is to study the synthesis of GFP chromophore analogs via a cyclization reaction. N-acylglycines were heated with various benzaldehydes and sodium acetate in acetic anhydride to form a series of 4-benzylidene-5-oxazolinone derivatives. The oxazolinones were treated with primary amines or C-terminal protected amino acids under room temperature to afford the ring-opened adducts, which contained the 2-acylamido-3-arylacrylamide moiety. Our investigation has found that the desired 4-benzylidene-5-imidazolinone derivatives could be obtained in good yields when the ring-opened adducts were heated in pyridine. We have also demonstrated the generality of the methodology. When different N-acylglycines and primary amines were employed, a wide variety of 1- and 2-substituted 4-benzylidene-5-imidazolinones could be obtained. It is also applicable to various para-substituted benzaldehydes that would afford different substituents at the para-position of the benzylidene. We have successfully synthesized a series of 1,2-substituted-4-benzylidene-5-imidazolinone as the analogs of GFP chromophores, comprising CH3, Bn, CH2COOMe, CH2COOH, CH3CHCOOH, CH3CHCOOMe, H at 1-position; CH3, Ph, 2-phthalimidopropyl at 2-position; H, halide, CN, OH at the para-position of benzylidene. Our results have shown that our approach toward the 4-benzylidene-5-imidazolinones from ring-opening / ring-closing route is more facile and efficient than the existing methods.
Description
Keywords
螢光蛋白質, GFP