Total synthesis of mannosyl tryptophan and its derivatives
Total synthesis of mannosyl tryptophan and its derivatives
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DOI：
10.1002/chem.200390163
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发表时间：
2003-03-17
影响因子：
4.3
通讯作者：
Ito, Y
中科院分区：
文献类型：
--
作者：
Manabe, S;Marui, Y;Ito, Y
糖基化是蛋白质最重要的翻译后修饰或共翻译修饰之一，它通过影响亲本蛋白的高阶结构来影响其生物活性。最近，在各种蛋白质中发现了一种包含c -糖基化氨基酸的高度新颖的糖蛋白变体。成功地合成了一种这样的c -糖基氨基酸，即c -2- α - d - c -甘露糖酰基- l-色氨酸及其相关肽。甘露糖和简洁立体选择的方式，在色氨酸部分是通过开环苯基保护的1,2-无水甘露糖由锂化吲哚衍生物连接。经过官能团转化和脱保护步骤，以较高的总收率合成了糖氨基酸。立体异构体c -2- α - d - c -糖基吡喃酰基- l-色氨酸以类似的方法合成。此外，发现中间叠氮酸可以作为肽延伸的有用构建块。本文还报道了一种利用三嗪盐衍生物作为偶联剂，在不保护羟基的情况下合成糖肽键的方法。
Glycosylation is one of the most important post- or co-translational modifications of proteins, which affects the biological activities of the parent proteins by influencing the higher-order structure. Recently, a highly novel variant of glycoproteins that incorporate a C-glycosylated amino acid was identified in various proteins. The total synthesis of one such C-glycosyl amino acid, namely, C-2-alpha-D-C-mannosylpyranosyl-L-tryptophan and related peptides were successfully achieved. The mannose and concise and stereoselective manner, in tryptophan moieties were connected via ring opening of benzyl-protected 1,2-anhydro-mannose by a lithiated indole derivative. After the functional group conversion and deprotection steps, the glyco-amino acid was synthesized,in a high overall yields. The stereoisomer, C-2-alpha-D-C-glycosylpyranosyl-L-tryptophan was synthesized in a similar way. Furthermore, it was revealed that the intermediate azido acid can serve as a useful building block for peptide elongation. A synthetic route for the peptide bond formation of a glycopeptide, without protection of the hydroxyl groups, using the triazine salt derivative as a coupling reagent is also reported.