Unified Total Synthesis of Polyoxin J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions
Unified Total Synthesis of Polyoxin J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions
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基于脱羰自由基偶联反应的多氧菌素J、L和氟化类似物的统一全合成
DOI：
10.1002/ange.201706671
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
and M. Inoue
中科院分区：
文献类型：
--
作者：
H. Fujino;M. Nagatomo;A. Paudel;S. Panthee;H. Hamamoto;K. Sekimizu;and M. Inoue
多抗素 J (1 a) 和L (1 b) 是重要的核苷类抗生素。 1 a和1 b的复杂且密集功能化的二肽结构分别含有胸腺嘧啶和尿嘧啶核碱基。在此，我们报道了具有三氟胸腺嘧啶和氟尿嘧啶结构的1 a、1 b及其人工类似物1 can和1 d的统一全合成。 α-烷氧基酰基碲化物和手性乙醛肟醚之间的脱羰自由基偶联导致1 a-d的核糖核苷α-氨基酸结构的化学和立体选择性构建，而不破坏预先安装的核碱基。通过制备 1 a-d 的三羟基正缬氨酸部分，进一步证明了基于自由基的方法的高适用性。将两个氨基酸片段连接并精细化为1 a–d（最长线性序列：11 步）。以这种方式组装的化合物 1 a 和 1 b 对真正的真菌表现出有效的活性，而只有 1 d 对革兰氏阳性细菌具有活性。
Polyoxins J (1 a) and L (1 b) are important nucleoside antibiotics. The complex and densely functionalized dipeptide structures of1 aand1 bcontain thymine and uracil nucleobases, respectively. Herein we report the unified total synthesis of1 a,1 b, and their artificial analogues1 cand1 dwith 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 of1 a–dwithout damaging the preinstalled nucleobases. The high applicability of the radical‐based methodology was further demonstrated by preparation of the trihydroxynorvaline moiety of1 a–d. The two amino acid fragments were connected and elaborated into1 a–d(longest linear sequence: 11 steps). Compounds1 aand1 bassembled in this way exhibited potent activity against true fungi, while only1 dwas active against Gram‐positive bacteria.