Synthesis of (±)-2′,3′-didehydro-2′,3′-dideoxy nucleosides via a modified Prins reaction and palladium(0) catalysed coupling

Abstract

Cyclopentenyl allylic acetates have been prepared in diastereoisomerically enriched form by modification of the Prins reaction. Palladium(o) catalysed coupling between these allylic acetates and a heteroaromatic base provides a highly convergent and direct route for synthesising car bocycl i c 2',3' -d ide h y d ro -2',3'd ideoxy n ucleosides. The met hod is exem pl if ied by the c o u pl i ng reaction with adenine which yields ( & ) -2',3'-didehydro-2',3'-dideoxyaristeromycin 5'-O-acetate 22 in 50% yield. This has been converted in two steps into ( + ) -aristeromycin triacetate 5.Nucleosides exhibit a wide range of biological properties of both agrochemical and pharmaceutical interest.' Amongst the many structural types, carbocyclic nucleosides are of special interest, since they are not susceptible to degradation in viuo by nucleosidases and phosphorylases.2 For example carbovir 1 and its adenine analogue 2 exhibit antiviral a ~t i v i t y . ~ Current Paper 1 /03089B

Ikaros expression as a marker for lymphoid progenitors during zebrafish development

“…Palladium(0) derivatives are known to catalyze N ‐allylation reactions of free (NH)‐imidazoles with allylic electrophiles 117–120. In 1991, Lindell and co‐workers found that imidazole undergoes Pd(PPh 3 ) 4 ‐catalyzed N‐ allylation by treatment with a diastereoisomerically enriched mixture of 3‐acetoxy‐4‐(acetoxymethyl)cyclopentene in THF in the presence of Et 3 N (Scheme ) 117…”

Facile Synthesis of Fluorinated Benzofuro- and Benzothieno[2,3-b]pyridines, α-Carbolines and Nucleosides Containing the α-Carboline Framework

“…Palladium-catalyzed allylation of a heterobase possessing a free NH position is one of the highly useful strategies for assembling carbocyclic nucleosides. 16 We have successfully used this method for the synthesis of carbocyclic nucleoside 41 from carboline 16a and cis-diacetate 32.…”

“…Carbocyclic nucleosides 37 and 39 were obtained according to the Mitsunobu protocol. 16 A soln of DEAD (8.9 mmol) in anhyd MeCN was added dropwise to a stirred, cooled soln (0°C) of a carbocyclic sugar (3.7 mmol).…”

The Prins Reaction: Advances and Applications

“…The cis-diacetate 146 was readily prepared using a ptoluenesulfonic acid-catalyzed Prins reaction between cyclopentadiene and paraformadehyde in acetic acid: the reaction was not completely stereo-and regioselective, giving also the other three isomers [48]. Compound 146 and the corresponding deprotected diol are synthetically interesting because can be transformed into carbocyclic nucleoside derivatives [49].…”