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Enantioselective total synthesis of parnafungin A1 and 10a-epi-hirtusneanine.

Jiawei SunWei GuHe YangWenjun Tang
Published in: Chemical science (2021)
The first and enantioselective total synthesis of the heterodimeric biaryl antifungal natural product parnafungin A1 as well as complex biaryl tetrahydroxanthone 10a-epi-hirtusneanine is accomplished, by employing cross-coupling through the benzoxaborole strategy to construct their sterically hindered biaryl cores. Besides the powerful Suzuki-Miyaura cross-coupling, the synthesis of parnafungin A1 also features a highly diastereoselective oxa-Michael addition to construct a tetrahydroxanthone skeleton, and an effective Zn-mediated reductive cyclization-Mitsunobu sequence to furnish the isoxazolidinone structure. Key innovations in total synthesis of 10a-epi-hirtusneanine include the employment of DTBS protection for functional group manipulation on the tetrahydroxanthone skeleton, stereoselective methylations, and complete reversal of the stereochemistry of the C5-hydroxy group using oxidation/Evans-Saksena reduction, as well as the strategy of preparing both complex tetrahydroxanthone monomers from the same chiral intermediate 25.
Keyphrases
  • candida albicans
  • heavy metals
  • hydrogen peroxide
  • escherichia coli
  • cystic fibrosis
  • ionic liquid
  • mass spectrometry
  • pseudomonas aeruginosa
  • amino acid
  • risk assessment