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Unified Total Synthesis of Polyoxins J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions
Author(s) -
Fujino Haruka,
Nagatomo Masanori,
Paudel Atmika,
Panthee Suresh,
Hamamoto Hiroshi,
Sekimizu Kazuhisa,
Inoue Masayuki
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201706671
Subject(s) - moiety , chemistry , nucleobase , stereochemistry , thymine , uracil , stereoselectivity , nucleoside , dipeptide , combinatorial chemistry , amino acid , organic chemistry , catalysis , biochemistry , dna
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.