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. 2020 Mar 24;11(25):6521-6526.
doi: 10.1039/d0sc01260b.

Late-stage C(sp2)-H and C(sp3)-H glycosylation of C-aryl/alkyl glycopeptides: mechanistic insights and fluorescence labeling

Jun Wu  1 , Nikolaos Kaplaneris  1 , Shaofei Ni  1 , Felix Kaltenhäuser  1 , Lutz Ackermann  1   2
Affiliations

Late-stage C(sp2)-H and C(sp3)-H glycosylation of C-aryl/alkyl glycopeptides: mechanistic insights and fluorescence labeling

Jun Wu et al. Chem Sci. .

Abstract

C(sp3)-H and C(sp2)-H glycosylations of structurally complex amino acids and peptides were accomplished through the assistance of triazole peptide-isosteres. The palladium-catalyzed peptide-saccharide conjugation provided modular access to structurally complex C-alkyl glycoamino acids, glycopeptides and C-aryl glycosides, while enabling the assembly of fluorescent-labeled glycoamino acids. The C-H activation approach represents an expedient and efficient strategy for peptide late-stage diversification in a programmable as well as chemo-, regio-, and diastereo-selective fashion.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. (a) Selected C-aryl glycosides and glycopeptides. (b) C(sp3)–H glycosylation of labeled amino acids and peptides.
Scheme 1
Scheme 1. Scope of glycosylation with TAM and AQ as auxiliaries. (a) 100 °C.
Scheme 2
Scheme 2. Scope of C(sp2)–H glycosylation to C-aryl glycosides.
Scheme 3
Scheme 3. Scope of glycosylation of terminal peptides and hybrids.
Fig. 2
Fig. 2. H/D exchange and KIE experiments.
Fig. 3
Fig. 3. Calculated Gibbs free energy profiles for the oxidative addition and reductive elimination steps in kcal mol−1 at the ωB97X-D/6-311++G(d,p), SDD(Pd, I, Ag) + SMD(1,4-dioxane)//ωB97X-D/6-31G(d), LANL2DZ(Pd, I, Ag) level of theory.
Fig. 4
Fig. 4. The 3D structures and the non-covalent interactions visualized through NCI-plots of the transition state TS1–2 (strong and weak attractive interactions are given in blue and green, respectively, while red corresponds to strong repulsive interactions).
Scheme 4
Scheme 4. Scope of glycosylation of terminal peptides.
Scheme 5
Scheme 5. Scope of BODIPY labeled glycoamino acids.
See this image and copyright information in PMC

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