Ferrier Carbocyclization-Mediated Synthesis of Enantiopure Azido Inositol Analogues

Alex P. Ausmus, Maxwell Hogue, Justin L. Snyder, Sarah R. Rundell, Krestina M. Bednarz, Nicholas Banahene, Benjamin M. Swarts

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 β-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.

Original languageEnglish
Pages (from-to)3182-3191
Number of pages10
JournalJournal of Organic Chemistry
Volume85
Issue number5
DOIs
StatePublished - Mar 6 2020

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