Highly stereoselective N-terminal functionalization of small peptides by chiral phase-transfer catalysis
Highly stereoselective N-terminal functionalization of small peptides by chiral phase-transfer catalysis
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DOI：
10.1002/anie.200390167
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Maruoka, K
中科院分区：
文献类型：
--
作者：
Ooi, T;Tayama, E;Maruoka, K
肽修饰是一种重要而灵活的合成概念，可在天然肽作为药物的应用中有效筛选靶标并优化先导结构。[1, 2] 将侧链直接引入肽主链是制备非天然肽的有效方法。非手性甘氨酸亚基通常用于此目的 [3]，甘氨酸烯醇化物、[4±8] 自由基、[9±11] 和甘氨酸阳离子当量 [12, 13] 已在膜中被吸收。据报道，活性 Pyc 位点是 ORR 的有效催化剂，[3b, 7]，因此，净化 O2 对于反应过程中 H2O2 的形成至关重要。纯 H2O2 的对照实验仅获得约 47% 的转化率，且选择性较差（表 1）。然而，Pyc 和 [Ru (bpy) 3] 2þ 在 SOR 中的协助得到了前面提到的间接电化学研究的支持。然后通过将 4.5 î 2 cm j NPycxÀRu (bpy) j 放入 CH3CN (30 mL)、H2O (40 mL) 和 17 mm RSCH3(R 1/4 Ph、PhCOCH3 和 PhOCH3) 的混合物中（pH 1）进行评估，并在照明（500 W 卤素灯）下持续吹扫 O2 3 小时，从而评估 SOR 的效率。通过使用旋转真空系统蒸发分离的反应产物在CHCl 3 中的溶液来简单地分析产物。所有反应均以> 90%的产率产生单一亚砜产物（即，在TLC板上未观察到任何砜，并通过NMR和质谱研究进一步证实）。清楚地证明了当前方法的高选择性。最后，用 PhSCH3 进行了三个重复实验来测试 j NPycxÀRu (bpy) j 系统的可回收性，并观察到几乎相同的产率。总之，我们证明了在含有 Pyc 催化剂和 [Ru (bpy) 3] 的新型异质多组分 nafion 膜上将硫化物清洁且高选择性地光化学氧化为亚砜。 2+光敏剂。与传统方法相比，多组分膜具有高亚砜选择性、无污染、易于产物分离和可回收性质等明显优势。目前正在进行进一步的研究，以将该反应的范围扩大到含有更复杂有机结构的硫化物以及宏观合成。
Peptide modification is an essential yet flexible synthetic concept for screening targets efficiently and optimizing lead structures in the application of naturally occurring peptides as pharmaceuticals.[1, 2] The introduction of side chains directly to a peptide backbone is a powerful method for preparing nonnatural peptides. The achiral glycine subunit has generally been used for this purpose [3] and glycine enolates,[4±8] radicals,[9±11] and glycine cation equivalents [12, 13] have been exabsorption in the membrane. The active Pyc site was reported to be an efficient catalyst for the ORR,[3b, 7] and hence, the purging O2 is essential for the formation of H2O2 during the reaction. The control experiment in pure H2O2 gave only about 47% conversion with poor selectivity (Table 1). However, the assistance of Pyc and [Ru (bpy) 3] 2þ in the SOR was supported by the indirect electrochemical studies mentioned earlier. The efficiency of the SOR was then evaluated by putting a 4.5 î 2 cm j NPycxÀRu (bpy) j in a mixture of CH3CN (30 mL), H2O (40 mL), and 17 mm RSCH3(R ¼ Ph, PhCOCH3, and PhOCH3) at pH 1, with constant purging of O2 under illumination (500 W halogen lamp) for 3 h. The products were analyzed simply by evaporation of the solution of the separated reaction product in CHCl3 with a rotaryvacuum system. All reactions gave a single product of sulfoxide (that is, no sulfone was observed on the TLC plate and was further confirmed by NMR and mass spectroscopic studies) in> 90% yield. The high selectivity of the current approach was clearly demonstrated. Finally, three repeated experiments were performed with PhSCH3 to test the recyclability of the j NPycxÀRu (bpy) j system, and almost the same yield was observed.In conclusion, we have demonstrated a clean and highly selective photochemical oxidation of sulfide to sulfoxide on a novel heterogeonous multicomponent nafion membrane containing a Pyc catalyst and a [Ru (bpy) 3] 2þ photosensitizer. The high sulfoxide selectivity, lack of pollution, ease of product separation, and recyclable nature of the muticomponent membrane has a clear advantage over classical approaches. Further investigations are currently underway to expand the scope of this reaction to sulfide compounds containing more complicated organic structures and to a macroscale synthesis.