Regioselective Synthesis of Multiple Thioether-Bridged Peptides via a One-Pot Reaction
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Summary
This summary is machine-generated.The SeODR strategy enables efficient synthesis of diverse bicyclic and glycopeptides. This one-pot method accommodates various cross-linkers, yielding complex cyclic peptides with glycosylation.
Area Of Science
- Organic Chemistry
- Peptide Synthesis
- Glycochemistry
Background
- Bicyclic peptides (BPs) are crucial in drug discovery due to their enhanced stability and potency.
- Existing methods for BP synthesis often involve multiple steps and limited structural diversity.
- The SeODR strategy offers a promising approach for peptide modification and cyclization.
Purpose Of The Study
- To adapt and apply the SeODR strategy for the synthesis of diverse bicyclic peptides (BPs).
- To develop novel monosaccharide-based cross-linkers for creating bicyclic glycopeptide conjugates (BGPs).
- To synthesize a complex tricycle glycopeptide conjugate (TGP) demonstrating the versatility of the combined strategies.
Main Methods
- Utilized the SeODR (selenium-driven oxidative deprotection and rearrangement) strategy for BP synthesis.
- Prepared novel monosaccharide-based cross-linkers via click chemistry conjugation of m-xylyl with glucose, mannose, and galactose.
- Employed a one-pot reaction approach for the synthesis of BPs, BGPs, and the TGP.
Main Results
- Successfully synthesized 15 bicyclic peptides (BPs) with varying thioether linkages in good yields.
- Demonstrated the compatibility of multiple cross-linkers (xylyl, BBP, BBMP, DCA, DCTZ) with the SeODR approach.
- Achieved the first synthesis of seven bicyclic glycopeptide conjugates (BGPs) and one tricycle glycopeptide conjugate (TGP) using the SeODR strategy and novel cross-linkers.
Conclusions
- The SeODR strategy is highly effective for the one-pot synthesis of structurally diverse bicyclic peptides.
- The developed monosaccharide-based cross-linkers are compatible with the SeODR approach, enabling BGP synthesis.
- The combined strategies provide a convenient and versatile platform for constructing complex, glycosylated cyclic peptides.
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