6533b7ddfe1ef96bd1273e7b

RESEARCH PRODUCT

Modular Solid-Phase Synthesis of Antiprotozoal Barnesin Derivatives

Dávid RomanLuka RagužFrancois KeiffFabian BarthelsFlorian MeyerChristine BeemelmannsFlorian KlossTanja Schirmeister

subject

medicine.drug_classAntiprotozoal AgentsChemistry Techniques Synthetic010402 general chemistry01 natural sciencesBiochemistrychemistry.chemical_compoundSolid-phase synthesisPeptide synthesismedicineSolid-Phase Synthesis TechniquesHumansPhysical and Theoretical ChemistrySolid-Phase Synthesis Techniqueschemistry.chemical_classificationNatural productMolecular Structure010405 organic chemistryOrganic ChemistryCombinatorial chemistry0104 chemical sciencesAmino acidCysteine EndopeptidaseschemistryReagentAntiprotozoalCysteine

description

Here, we applied and optimized a solid support (SP)-based Horner-Wadsworth-Emmons reagent to prepare SP-bound vinylogous amino acids. Subsequent SP-based peptide synthesis, global deprotection, and chemical modifications yielded 14 lipodipeptides carrying vinylogous amino acids, including the natural product barnesin A (1). Biological evaluation revealed that several synthesized derivatives show micromolar to nanomolar inhibitory activity against papain-like cysteine proteases, human cathepsin L, and rhodesain.

yearjournalcountryeditionlanguage
2020-03-26Organic Letters
10.1021/acs.orglett.0c00723http://dx.doi.org/10.1021/acs.orglett.0c00723