Sivets Grigorii, Sivets Aleksey, Synthesis of 2-Chloro-2′-Deoxyadenosine (Cladribine) and New Purine Modified Analogues, Journal of New Developments in Chemistry, Volume 3, Issue 4, 2021, Pages 1-10, ISSN 2377-2549, https://doi.org/10.14302/issn.2377-2549.jndc-21-4017.
(https://oap-researcharticles.org/jndc/article/1732)
Abstract: Theefficient two-step synthesis of 2-chloro-2′-deoxyadenosine (cladribine) via the anion glycosylation of purine potassium salt with the glycosyl chloride in binary solvent mixtures is described. A new method for preparation of diprotected 2-chloro-6-fluoropurine 2′-deoxy-β- D-riboside was developed by treatment of the 2,6-dichloropurine precursor with diethylaminosulfur trifluoride (DAST). Novel N6-alkylated cladribine analogue was synthesized by amination of acylated 2,6-dihalogenopurine nucleosides. It was found that a mild hydrolysis reaction of acylated 2-chloro-6-fluoropurine 2′-deoxy-β-D-riboside gave rise to new purine hydroxylated nucleoside.
Keywords: Anticancer purine nucleoside; glycosyl chloride; stereoselective anion glycosylation; fluorination reaction; mechanism