Solid-Phase Total Synthesis of Bogorol A: Stereocontrolled Construction of Thermodynamically Unfavored (E)-2-Amino-2-butenamide

Tomoya Yamashita, Takefumi Kuranaga, and Masayuki Inoue, Org. Lett., Article ASAP  Publication Date (Web): April 13, 2015  Copyright © 2015 American Chemical Society

Bogorol A [(E)-1], a potent antibiotic against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp., possesses a thermodynamically unfavored (E)-2-amino-2-butenamide within its linear dodecapeptide sequence. The highly efficient totalsynthesis of natural (E)-isomer (E)-1 and its artificial (Z)-isomer (Z)-1 by employing a full solid-phase strategy is reported. The (E)- and (Z)-2-amino-2-butenamide moieties were stereoselectively constructed by applying traceless Staudinger ligation on the resin. Interestingly, (E)- and (Z)-1 showed comparable antimicrobial activity (MIC = 4 μg/mL).