Scalable synthesis of Fmoc-protected GalNAc-threonine amino acid and T(N) antigen via nickel catalysis.
Scalable synthesis of Fmoc-protected GalNAc-threonine amino acid and T(N) antigen via nickel catalysis.
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DOI：
10.1021/acs.orglett.5b00780
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发表时间：
2015-04-17
期刊：
影响因子：
5.2
通讯作者：
Nguyen HM
中科院分区：
文献类型：
--
作者：
Yu F;McConnell MS;Nguyen HM
描述了Fmoc保护的GalNAc-苏氨酸氨基酸和TN抗原的高α-选择性和可放大的合成，以克规模（0.5 - 1克）。具有挑战性的1，2-顺式-2-氨基糖苷键通过由Ni（4-F-PhCN）4（OTf）2介导的苏氨酸单元与C（2）-N-邻-（三氟甲基）亚苄基氨基三卤代乙酰亚胺酯供体的偶联来解决。以66%（3.77 g）的仅α-选择性获得所需的1，2-顺式-2-氨基糖苷，随后转化成Fmoc保护的GalNAc-苏氨酸和TN抗原。这种操作简单的方法不再需要使用常用的C（2）-叠氮基供体，并且克服了与1，2-顺式键合的合成相关的许多限制。
The highly α-selective and scalable synthesis of the Fmoc-protected GalNAc-threonine amino acid and TN antigen in gram scale (0.5 – 1 gram), is described. The challenging 1,2-cis-2-amino glycosidic bond is addressed through a coupling of threonine units with C(2)-N-ortho-(trifluoromethyl)benzylidenamino trihaloacetimidate donors mediated by Ni(4-F-PhCN)4(OTf)2. The desired 1,2-cis-2-amino glycoside was obtained in 66% (3.77 g) with α-only selectivity and subsequently transformed into the Fmoc-protected GalNAc-threonine and TN antigen. This operationally simple procedure no longer requires utilization of the commonly used C(2)-azido donors and overcomes many of the limitations associated with the synthesis of 1,2-cis linkage.