Unified Total Synthesis of Polyoxins J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions
Haruka Fujino
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
Search for more papers by this authorDr. Masanori Nagatomo
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
Search for more papers by this authorDr. Atmika Paudel
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorDr. Suresh Panthee
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorDr. Hiroshi Hamamoto
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorProf. Dr. Kazuhisa Sekimizu
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorCorresponding Author
Prof. Dr. Masayuki Inoue
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
Search for more papers by this authorHaruka Fujino
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
Search for more papers by this authorDr. Masanori Nagatomo
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
Search for more papers by this authorDr. Atmika Paudel
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorDr. Suresh Panthee
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorDr. Hiroshi Hamamoto
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorProf. Dr. Kazuhisa Sekimizu
Teikyo University, Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, 192-0395 Japan
Search for more papers by this authorCorresponding Author
Prof. Dr. Masayuki Inoue
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
Search for more papers by this authorAbstract
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.
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