Salinas Juan C, Migawa Michael T, Merner Bradley L, Hanessian Stephen
Department of Chemistry, Université de Montréal , Montréal, Québec H3C 3J7, Canada.
J Org Chem. 2014 Dec 5;79(23):11651-60. doi: 10.1021/jo502320y. Epub 2014 Nov 17.
Approaches to the synthesis of the constrained 5-methyluracil nucleoside (S)-cEt-BNA, a key "gapmer" unit in a number of biologically relevant antisense oligonucleotides, are described using 5-methyluridine as starting material. In the shorter synthesis, a nine-step linear sequence afforded a O-protected (S)-cEt-BNA consisting of a [2.2.1]dioxabicycloheptane core in 7% overall yield. A competing reaction in an intramolecular cyclization of a tosylate led to a bicyclic oxetane.
描述了以5-甲基尿苷为起始原料合成受限5-甲基尿嘧啶核苷(S)-cEt-BNA的方法，(S)-cEt-BNA是许多具有生物学相关性的反义寡核苷酸中的关键“gapmer”单元。在较短的合成路线中，一个九步线性序列得到了一个O-保护的(S)-cEt-BNA，其具有[2.2.1]二氧杂双环庚烷核心，总产率为7%。在一个甲苯磺酸酯的分子内环化反应中，一个竞争反应导致了双环氧杂环丁烷的形成。
