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Synthesis 2020; 52(03): 417-423
DOI: 10.1055/s-0039-1690732
DOI: 10.1055/s-0039-1690732
paper
Practical Synthesis of Fludarabine and Nelarabine
The project was supported by the National Natural Science Foundation of China (NO. 21676131, 21462019,), the Jiangxi Provincial Department of Science and Technology (No. 20143ACB20012), the Education Department of Jiangxi Province (No. 170673) and the Jiangxi Science & Technology Normal University (Doctor Startup Fund 2018BSQD022).Further Information
Publication History
Received: 09 September 2019
Accepted after revision: 07 October 2019
Publication Date:
30 October 2019 (online)
Abstract
A new practical synthesis strategy has been developed to access the β-d-arabinofuranosyl purine nucleosides fludarabine and nelarabine. In our approach, an ortho-alkyne benzoyl ester is transiently introduced as a neighbouring-participation group in Vorbrüggen glycosylation to afford the corresponding β-nucleoside exclusively. The latter was further removed efficiently by using freshly prepared Ph3PAuOTFA to give the corresponding 2′-OH nucleosides without transesterification. After reversion of the configuration of 2′-OH and deprotection, fludarabine and nelarabine were obtained in high yield and purity.
Key words
fludarabine - nelarabine - gold(I) catalysis - total synthesis - ortho-alkyne benzoyl ester - β-d-arabinofuranosyl purine nucleosides - Vorbrüggen glycosylationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690732. Included are NMR spectra for compounds 1, 2, (11–14)a, (11–14)b, and crystal data and structure refinement for 12b and 13a.
- Supporting Information
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