Solution versus Fluorous versus Solid-Phase Synthesis of 2,5-Disubstituted 1,3-Azoles. Preliminary Antibacterial Activity Studies
Solution versus Fluorous versus Solid-Phase Synthesis of 2,5-Disubstituted 1,3-Azoles. Preliminary Antibacterial Activity Studies
复制标题
DOI：
10.1021/jo9016265
复制
发表时间：
2009-12-04
影响因子：
3.6
通讯作者：
Fustero, Santos
中科院分区：
文献类型：
--
作者：
Sanz-Cervera, Juan F.;Blasco, Rauel;Fustero, Santos
合成了一个具有氧(硫)唑骨架和2和5位结构多样性的化合物的小型文库。受保护的甘氨酸的双酰化反应得到中间体α-氨基-β-酮酯，这些中间体可以脱水得到1，3-恶唑或与Lawesson试剂反应得到1，3-噻唑。这个程序的设计考虑到了它对氟技术的适应。因此，当使用在酯部分带有氟标记的受保护甘氨酸作为起始原料时，无需柱层析就可以容易地完成中间化合物的合成，并以良好到极好的产率进行纯化，从而为制备这些生物活性化合物的小文库提供了合适的入口。对所制备的氧杂硫唑进行了抗菌活性测定，其中几个化合物对金黄色葡萄球菌具有抗菌活性。
A small library of compounds with an oxa(thia)zole scaffold and structural diversity in both positions 2 and 5 has been synthesized. Double acylation of a protected glycine affords intermediate alpha-amido-beta-ketoesters, which in turn can be dehydrated to afford 1,3-oxazoles or reacted with Lawesson's reagent to furnish 1,3-thiazoles. This procedure was designed with its adaptation to fluorous techniques in mind. Thus, when a protected glycine With a fluorous tag in the ester moiety IS used as a starting material, the synthesis can be easily completed Without column chromatography purification of intermediate compounds with good to excellent yields, thus affording a Suitable entry to the preparation of small libraries of these bioactive compounds. The prepared oxa(thia)zoles were assayed for their antibacterial activity, and several of them were active against Staphylococcus aureus.