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Solid-Phase Total Synthesis of Bogorol A: Stereocontrolled Construction of Thermodynamically Unfavored
Tomoya Yamashita1, Takefumi Kuranaga1, Masayuki Inoue1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
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 total synthesis 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).
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