Regiodivergent
Glycosylations of 6‑Deoxy-erythronolide
B and Oleandomycin-Derived Macrolactones Enabled by Chiral Acid Catalysis
Jia-Hui Tay
Alonso J. Argüelles
Matthew D. DeMars
Paul M. Zimmerman
David H. Sherman
Pavel Nagorny
10.1021/jacs.7b03198.s002
https://acs.figshare.com/articles/journal_contribution/Regiodivergent_Glycosylations_of_6_Deoxy-erythronolide_B_and_Oleandomycin-Derived_Macrolactones_Enabled_by_Chiral_Acid_Catalysis/5116363
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.
2017-06-16 20:33:59
chiral acids
C 11 positions
macrolactone
Regiodivergent Glycosylations
Oleandomycin-Derived Macrolactones Enabled
rr
SPINOL-based CPAs
glycosyl
reaction mechanism
C 5 positions
anomeric phosphates
introduction
C 3 alcohol
boronic acids
chiral catalysts
traceless protection
C 11 position
control site-selectivity
BINOL-based chiral phosphoric acids
reactive intermediates
selectivity switch