Synthesis, Table of Contents Synthesis 2020; 52(03): 417-423DOI: 10.1055/s-0039-1690732 paper © Georg Thieme Verlag Stuttgart · New YorkPractical Synthesis of Fludarabine and Nelarabine Authors Chunyang Shen Jiang Liu Wenliang Ouyang Haixin Ding∗ Jiang Bai Qiang Xiao ∗ Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) 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 Key wordsfludarabine - nelarabine - gold(I) catalysis - total synthesis - ortho-alkyne benzoyl ester - β-d-arabinofuranosyl purine nucleosides - Vorbrüggen glycosylation Full Text References References 1a Seley-Radtke KL, Yates MK. Antiviral Res. 2018; 154: 66 1b Yates MK, Seley-Radtke KL. Antiviral Res. 2019; 162: 5 1c Shelton J, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF. Chem. Rev. 2016; 116: 14379 2a Jordheim LP, Durantel D, Zoulim F, Dumontet C. Nat. Rev. Drug Discovery 2013; 12: 447 2b De Clercq E, Li G. Clin. Microbiol. Rev. 2016; 29: 695 3a Szlenkier M, Boryski J. Curr. Org. Chem. 2019; 23: 409 3b Chen Z, Cox BD, Garnier-Amblard EC, McBrayer TR, Coats SJ, Schinazi RF, Amblard F. Bioorg. Med. Chem. Lett. 2017; 27: 5296 3c Prakash TP, Bhat B. Curr. Top. Med. Chem. 2007; 7: 641 4a Sivets GG, Amblard F, Schinazi RF. Tetrahedron 2019; 75: 2037 4b Stairs S, Powner MW. Synlett 2017; 28: 2650 4c Ranjbarian F, Vodnala M, Alzahrani KJ. H, Ebiloma GU, de Koning HP, Hofer A. Antimicrob. Agents Chemother. 2017; 61: e02719-16 5a Hallek M. Am. J. Hematol. 2017; 92: 946 5b Robak P, Robak T. Cancer Treat. Rev. 2013; 39: 851 5c Reilly KM, Kisor DF. OncoTargets Ther. 2009; 2: 219 6 Montgomery JA, Clayton SD, Shortnacy AT. J. Heterocycl. Chem. 1979; 16: 157 7a Kulikowski T, Zawadzki Z, Shugar D, Descamps J, De Clercq E. J. Med. Chem. 1979; 22: 647 7b Zissis E, Glaudemans CP. J. Carbohydr. Res. 1976; 50: 292 7c Okamoto K, Kondo T, Goto T. Bull. Chem. Soc. Jpn. 1986; 59: 1915 8a Callam C, Lowary T. J. Chem. Educ. 2001; 78: 312 8b Coyle T, Brumer H, Stubbs KA. Can. J. Chem. 2015; 93: 1176 8c Senf D, Ruprecht C, de Kruijff GH. M, Simonetti SO, Schuhmacher F, Seeberger PH, Pfrengle F. Chem. Eur. J. 2017; 23: 3197 9 Kshirsagar SW, Deshpande MS, Sonawane SP, Maikap GC, Gurjar MK. Org. Process Res. Dev. 2012; 16: 840 10a Secrist JA. III, Shortnacy AT, Montgomery JA. J. Med. Chem. 1988; 31: 405 10b Herbal K, Kitteringham J, Voyle M, Whitehead AJ. Tetrahedron Lett. 2005; 46: 2961 11a Xia R, Guo Z, Qin BW, Ji ZY, Xie MS, Qu GR, Guo HM. Chin. J. Org. Chem. 2014; 34: 1154 11b Kumar AB, Manetsch R. Eur. J. Org. Chem. 2014; 3551 11c Ishido Y, Nakazaki N, Sakairi N. J. Chem. Soc., Perkin Trans. 1 1979; 2088 12a Nobile M, Medici R, Terreni M, Lewkowicz ES, Iribarren AM. Process Biochem. 2012; 47: 2182 12b Zuffi G, Ghisotti D, Oliva I, Capra E, Frascotti G, Tonon G, Orsini G. Biocatal. Biotransform. 2004; 22: 25 13 Konstantinova ID, Antonov KV, Fateev IV, Miroshnikov AI, Stepchenko VA, Baranovsky AV, Mikhailopulo IA. Synthesis 2011; 1555 14 Ding H, Li C, Zhou Y, Hong S, Zhang N, Xiao Q. RSC Adv. 2017; 7: 1814 15a Li C, Ding H, Ruan Z, Zhou Y, Xiao Q. Beilstein J. Org. Chem. 2017; 13: 855 15b Ding H, Li C, Dong X, Cao B, Zhang N, Hong S, Xiao Q. Chin. J. Org. Chem. 2018; 38: 3351 16a Howell HG, Brodfuehrer PR, Brundidge SP, Benigni DA, Sapino CJr. J. Org. Chem. 1988; 53: 85 16b Brodfuehrer PR, Sapino CJr, Howell HG. J. Org. Chem. 1985; 50: 2597 17a Vorbruggen H, Ruh-Pohlenz C. Org. React. 2000; 55: 1 17b Ding H, Li W, Ruan Z, Yang R, Mao Z, Xiao Q, Wu J. Beilstein J. Org. Chem. 2014; 10: 1681 17c Dou Y.-H, Ding H.-X, Yang R.-C, Li W, Xiao Q. Chin. Chem. Lett. 2013; 24: 379 18 CCDC 1938040 (12b) and 1938039 (13a) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
