Ferrier Carbocyclization-Mediated Synthesis of Enantiopure Azido Inositol Analogues
Ferrier Carbocyclization-Mediated Synthesis of Enantiopure Azido Inositol Analogues
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DOI：
10.1021/acs.joc.9b03064
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发表时间：
2020-03-06
影响因子：
3.6
通讯作者：
Swarts, Benjamin M.
中科院分区：
文献类型：
--
作者：
Ausmus, Alex P.;Hogue, Maxwell;Swarts, Benjamin M.
叠氮化物修饰的肌醇（InoAz）类似物作为抑制剂是有价值的，并且已经显示出作为代谢化学报告者（mcr）标记真核细胞和分枝杆菌中含有肌醇的糖缀合物的前景，但是通过传统方法合成对构象纯的InoAz类似物具有挑战性。作为一种补充途径，我们研究了Ferrier碳环化反应在从现成的叠氮糖苷开始合成对映纯InoAz类似物中的应用。该方法结合对甲氧基保护基团，高效合成了3-叠氮-3-脱氧-和4-叠氮-4-脱氧-d -肌醇。由于不寻常的β消除反应，5-叠氮-5-脱氧-d -肌醇是不可接近的，其中叠氮阴离子作为离去基。报道的策略有望促进合成InoAz类似物作为真核和分枝杆菌系统中含肌醇糖缀合物的抑制剂或mcr的继续发展。
Azide-modified inositol (InoAz) analogues are valuable as inhibitors and have shown promise as metabolic chemical reporters (MCRs) for labeling inositol-containing glycoconjugates in eukaryotic cells and potentially in mycobacteria, but the synthesis of enantiomerically pure InoAz analogues via traditional approaches is challenging. As a complementary route, here we investigated the application of the Ferrier carbocyclization reaction to the synthesis of enantiopure InoAz analogues starting from readily available azido glucosides. Using this approach combined with a para-methoxybenzyl protecting group strategy, 3-azido-3-deoxy- and 4-azido-4-deoxy-D-myo-inositol were efficiently synthesized. 5-Azido-5-deoxy-D-myo-inositol was inaccessible due to an unusual beta-elimination reaction, wherein the azide anion acted as the leaving group. The reported strategy is expected to facilitate continued development of synthetic InoAz analogues as inhibitors or MCRs of inositol-containing glycoconjugates in eukaryotic and mycobacterial systems.