Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag
Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag
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DOI：
10.1016/j.tet.2011.05.073
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发表时间：
2011-09-02
期刊：
影响因子：
2.1
通讯作者：
Sunazuka, Toshiaki
中科院分区：
文献类型：
--
作者：
Hirose, Tomoyasu;Kasai, Takako;Sunazuka, Toshiaki
以3，4，5-三（十八烷氧基）苄基为羧基疏水保护基，液相全合成精氨酸，经16步线性反应，总收率44%。Argifin是一类新型的天然产物几丁质酶抑制剂，是一种水溶性很强的环状五肽，迄今为止，只有固相合成技术才能方便地制备该化合物及其衍生物。3，4，5-三（十八烷氧基）苄醇（HO-TAGa）及其酯是高度结晶的材料，并且高度能够溶解在极性较小的溶剂如二氯甲烷、苯、THF等中，但不溶于极性溶剂如甲醇和DMSO。HO-TAGa和基于Fmoc的肽合成的组合，以及通过从MeOH溶液中重结晶的简单纯化，提供了在液相中生产argifin的有效且实用的路线。(C)2011爱思唯尔有限公司保留所有权利。
A solution-phase total synthesis of argifin using 3,4,5-tris(octadecyloxy)benzyl tag as a hydrophobic protective group of carboxylic acid was developed to produce 44% overall yield for 16 linear steps. Argifin, a novel class of natural product chitinase inhibitor, is a highly water-soluble cyclic pentapeptide, so hitherto, only solid-phase synthesis techniques have been used to conveniently prepare the compound and its derivatives. 3,4,5-Tris(octadecyloxy)benzyl alcohol (HO-TAGa) and its esters are highly crystalline materials and highly capable of dissolving in less-polar solvents such as dichloromethane, benzene, THF, etc., but insoluble in polar solvents such as methanol and DMSO. The combination of HO-TAGa and Fmoc-based peptide synthesis, together with simple purification by recrystallization from MeOH solution, furnished an efficient and practical route of argifin production in the liquid-phase. (C) 2011 Elsevier Ltd. All rights reserved.