Tomoya Yamashita,Â Takefumi Kuranaga, andÂ Masayuki Inoue, Org. Lett., Article ASAP Â Publication Date (Web): April 13, 2015 Â Copyright Â© 2015 American Chemical Society
Bogorol A [(E)-1], a potent antibiotic against methicillin-resistantÂ Staphylococcus aureusÂ and vancomycin-resistantÂ Enterococcus spp., possesses a thermodynamically unfavored (E)-2-amino-2-butenamide within its linear dodecapeptide sequence. The highly efficient totalsynthesisÂ of natural (E)-isomer (E)-1Â and its artificial (Z)-isomer (Z)-1Â by employing a full solid-phase strategy is reported. The (E)-Â and (Z)-2-amino-2-butenamide moieties were stereoselectively constructed by applying traceless Staudinger ligation on the resin. Interestingly, (E)- and (Z)-1Â showed comparable antimicrobial activity (MIC = 4 Î¼g/mL).