We present a novel concept for the
in situ control of site-selectivity
of catalytic acetylations of partially protected sugars using light
as external stimulus and oligopeptide catalysts equipped with an azobenzene
moiety. The isomerizable azobenzene-peptide backbone defines the size
and shape of the catalytic pocket, while the π-methyl-l-histidine (Pmh) moiety transfers the electrophile. Photoisomerization
of the E- to the Z-azobenzene catalyst
(monitored via NMR) with an LED (λ = 365 nm) drastically changes
the chemical environment around the catalytically active Pmh moiety,
so that the light-induced change in the catalyst shape alters site-selectivity.
As a proof of principle, we employed (4,6-O-benzylidene)methyl-α-d-pyranosides, which provide a change in regioselectivity from
2:1 (E) to 1:5 (Z) for the monoacetylated
products at room temperature. The validity of this new catalyst-design
concept is further demonstrated with the regioselective acetylation
of the natural product quercetin. In situ irradiation NMR spectroscopy
was used to quantify photostationary states under continuous irradiation
with UV light.
Herein, we report the oligopeptide-catalyzed
site-selective acylation
of partially protected monosaccharides. We identified catalysts that
invert site-selectivity compared to N-methylimidazole,
which was used to determine the intrinsic reactivity, for 4,6-O-protected glucopyranosides (trans-diols)
as well as 4,6-O-protected mannopyranosides (cis-diols). The reaction yields up to 81% of the inherently
unfavored 2-O-acetylated products with selectivities
up to 15:1 using mild reaction conditions. We also determined the
influence of protecting groups on the reaction and demonstrate that
our protocol is suitable for one-pot reactions with multiple consecutive
protection steps.
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