Department of Chemistry , Fu Jen Catholic University , 510, Zhongzheng Rd. , Xinzhuang District, New Taipei City 24205 , Taiwan.
J Org Chem. 2018 Dec 21;83(24):14923-14932. doi: 10.1021/acs.joc.8b02002. Epub 2018 Nov 29.
The preparation of 2-deoxy-l-ribose derivatives or mirror image deoxyribonucleosides (l-deoxyribonucleosides) from d-ribose is reported. Starting from inexpensive d-ribose, an acyclic d-form carbohydrate precursor was synthesized to study a unique carbonyl translocation process. In this novel radical reaction, not only was the configuration of the sugar transformed from the d-form to the l-form, but also deoxygenation at the C(2) position of the sugar was successfully achieved. This is one of the most practical methods for converting a d-sugar to a 2-deoxy-l-sugar in a one-step reaction. To further identify the reaction product, radical reactions followed by treatment with 1,3-propanedithiol and then benzoylation were performed to afford a dithioacetal derivative. The stereochemistry and configuration of the 2-deoxy-l-ribose dithioacetal derivative were confirmed by its X-ray crystal structure. To further apply this methodology, a diethyl thioacetal derivative was formed, followed by selective benzoyl protection, and an NIS-initiated cyclization reaction to give the desired ethyl S-l-2-deoxyriboside, which can be used as a 2-deoxy-l-ribosyl synthon in the formal total synthesis of various l-deoxyribonucleosides, such as l-dT.
本文报道了从 D-核糖制备 2-脱氧-L-核糖衍生物或对映体脱氧核糖核苷（L-脱氧核糖核苷）。以廉价的 D-核糖为起始原料，合成了一种无环 D 型碳水化合物前体，以研究一种独特的羰基迁移过程。在这个新的自由基反应中，不仅糖的构型从 D 型转化为 L 型，而且糖的 C(2)位脱氧也成功实现了。这是在一步反应中将 D-糖转化为 2-脱氧-L-糖的最实用方法之一。为了进一步鉴定反应产物，进行了自由基反应，然后用 1,3-丙二硫醇处理，然后进行苯甲酰化，得到二硫缩醛衍生物。通过其 X 射线晶体结构证实了 2-脱氧-L-核糖二硫缩醛衍生物的立体化学和构型。为了进一步应用这种方法，形成了二乙基硫缩醛衍生物，然后进行选择性苯甲酰化保护和 NIS 引发的环化反应，得到所需的乙基 S-L-2-脱氧核糖苷，可作为各种 L-脱氧核糖核苷的 2-脱氧-L-核糖基合成子，例如 L-dT。
