Synthesis of macrocyclic precursors of the vioprolides.
Synthesis of macrocyclic precursors of the vioprolides.
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DOI：
10.1039/c8ob01756e
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发表时间：
2018-10
影响因子：
3.2
通讯作者：
E. Butler;Lucía Florentino;Damien Cornut;Gonzalo Gómez-Campillos;Hao Liu;A. Regan;E. Thomas
中科院分区：
文献类型：
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作者：
E. Butler;Lucía Florentino;Damien Cornut;Gonzalo Gómez-Campillos;Hao Liu;A. Regan;E. Thomas
维普利德是尚未合成的新型缩酚肽。然而，由于其新颖的生物活性和具有挑战性的化学结构，它们已被确定为重要的合成靶标。在合成含有 vioprolide D 的 (E)-脱氢丁酸和噻唑啉成分的修饰四肽的早期工作之后，在进一步合成含有 (E)-脱氢丁酸的中间体时遇到了问题。因此研究了制备vioprolides和类似物的第二种方法，其中在合成的最后阶段通过氧化硒消除引入(E)-和(Z)-脱氢丁酸。然后使用修饰的六肽和甘油二肽完成了对vioprolides的高级大环前体的收敛方法。在这项工作中，有必要将甘油酸酯的 2-羟基保护为其乙酸酯，而不是其 2,2,2-三氯乙氧基碳酸酯。对将所需的脱氢丁酸和噻唑啉成分引入高级中间体进行了初步研究。
The vioprolides are novel depsipeptides that have not been synthesized. However, they have been identified as important targets for synthesis because of their novel biological activities and challenging chemical structures. Following early work on the synthesis of a modified tetrapeptide that contained both the (E)-dehydrobutyrine and thiazoline components of vioprolide D, problems were encountered in taking an (E)-dehydrobutyrine containing intermediate further into the synthesis. A second approach to vioprolides and analogues was therefore investigated in which (E)- and (Z)-dehydrobutyrines were to be introduced by selenoxide elimination very late in the synthesis. A convergent approach to advanced macrocyclic precursors of the vioprolides was then completed using a modified hexapeptide and a dipeptidyl glycerate. In this work, it was necessary to protect the 2-hydroxyl group of the glycerate as its acetate and not as its 2,2,2-trichloroethoxycarbonate. Preliminary studies were carried out on the introduction of the required dehydrobutyrine and thiazoline components into advanced intermediates.