Regiodivergent Glycosylations of 6‑Deoxy-erythronolide B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis

Published on 2017-06-16T20:34:03Z (GMT) by
This work describes the first example of using chiral catalysts to control site-selectivity for the glycosyl­ations of complex polyols such as 6-deoxy­erythro­nolide B and oleando­mycin-derived macrolactones. The regio­divergent introduction of sugars at the C3, C5, and C11 positions of macrolactones was achieved by selecting appropriate chiral acids as catalysts or through introduction of stoichio­metric boronic acid-based additives. BINOL-based chiral phosphoric acids (CPAs) were used to catalyze highly selective glycosyl­ations at the C5 positions of macrolactones (up to 99:1 rr), whereas the use of SPINOL-based CPAs resulted in selectivity switch and glycosyl­ation of the C3 alcohol (up to 91:9 rr). Additionally, the C11 position of macrolactones was selectively function­alized through traceless protection of the C3/C5 diol with boronic acids prior to glycosyl­ation. Investigation of the reaction mechanism for the CPA-controlled glycosyl­ations revealed the involvement of covalently linked anomeric phosphates rather than oxo­carbenium ion pairs as the reactive intermediates.

Cite this collection

Tay, Jia-Hui; Argüelles, Alonso J.; DeMars, Matthew D.; Zimmerman, Paul M.; Sherman, David H.; Nagorny, Pavel (2017): Regiodivergent

Glycosylations of 6‑Deoxy-erythronolide

B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis. ACS Publications.

https://doi.org/10.1021/jacs.7b03198

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