- Total Synthesis of Nucleoside Antibiotics Amicetin, Plicacetin, and Cytosaminomycin A—D
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Amicetin and congeners constitute a small family of complex pyrimidine nucleosides, which exhibit strong antibiotic activities against Gram-positive bacteria and notably against strains of Mycobacterium tuberculosis. Herein, we report chemical synthesis of a series of disaccharide congeners of the amicetin family, including amicetin, plicacetin, and cytosaminomycin A—D. It is the first time for successful synthesis of amicetin, the prototypical member, and cytosaminomycins. The synthetic approach employs glycosyl N-phenyltrifluoroacetimidate and thioglycoside donors to construct the characteristic aminodeoxydisaccharides consisting of α-(1→4)-glycosidic linkage, uses gold(I)-catalyzed N-glycosylation to furnish 2-deoxy-β-nucleosides, and finally exploits amidation and global deprotection to complete the syntheses. It is noteworthy that the 3-O-protecting group in the 2-deoxydisaccharide donors is found to be crucial for a successful N-glycosylation to assemble the cytosaminomycin disaccharide nucleosides.
- Fu, Jiqiang,Xu, Peng,Yu, Biao
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p. 2679 - 2684
(2021/08/03)
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- Characterizing amosamine biosynthesis in amicetin reveals amig as a reversible retaining glycosyltransferase
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The antibacterial and antiviral agent amicetin is a disaccharide nucleoside antibiotic featuring a unique α-(1→4)-glycoside bond between amosamine and amicetose, characteristic of a retaining glycosylation. In this study, two key steps for amosamine biosynthesis were investigated: the N-methyltransferase AmiH was demonstrated to be requisite for the dimethylation in amosamine, and the glycosyltransferase AmiG was shown to be necessary for amosaminylation. Biochemical and kinetic characterization of AmiG revealed for the first time the catalytic reversibility of a retaining glycosyltransferase involved in secondary metabolite biosynthesis. AmiG displayed substrate flexibility by utilizing five additional sugar nucleotides as surrogate donors. AmiG was also amenable to sugar and aglycon exchange reactions. This study indicates that AmiG is a potential catalyst for diversifying nucleoside antibiotics and paves the way for mechanistic studies of a natural-product retaining glycosyltransferase.
- Chen, Ruidong,Zhang, Haibo,Zhang, Gaiyun,Li, Sumei,Zhang, Guangtao,Zhu, Yiguang,Liu, Jinsong,Zhang, Changsheng
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p. 12152 - 12155
(2013/09/23)
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