Unified Total Synthesis of Polyoxins J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions

Polyoxins J ( 1 a ) and L ( 1 b ) are important nucleoside antibiotics. The complex and densely functionalized dipeptide structures of 1 a and 1 b contain thymine and uracil nucleobases, respectively. Herein we report the unified total synthesis of 1 a , 1 b , and their artificial analogues 1 c and 1 d with trifluorothymine and fluorouracil structures. Decarbonylative radical coupling between α‐alkoxyacyl tellurides and a chiral glyoxylic oxime ether led to chemo‐ and stereoselective construction of the ribonucleoside α‐amino acid structures of 1 a – d without damaging the preinstalled nucleobases. The high applicability of the radical‐based methodology was further demonstrated by preparation of the trihydroxynorvaline moiety of 1 a – d . The two amino acid fragments were connected and elaborated into 1 a – d (longest linear sequence: 11 steps). Compounds 1 a and 1 b assembled in this way exhibited potent activity against true fungi, while only 1 d was active against Gram‐positive bacteria.