Novel 3′-deoxy analogs of the anti-HBV agent entecavir: synthesis of enantiomers from a single chiral epoxide

Regioselective ring-opening of epoxides with amines using Zn(ClO4)2–Al2O3 as a heterogeneous and recyclable catalyst

“…1 The versatility of this transformation is recognized well as it constitutes the key step for the synthesis of b 2 -adrenoceptor agonists, 2 anti HIV agents, 3 glycosidase inhibitor, 4 4-demethoxydaunomycine, 5 antimalarial agents, 6 liposidomycin B class of antibiotics, 7 taxoid side chain, 8 protein kinase C inhibitor balanol 9 and naturally occurring brassinosteroids, 10 a vast range of biologically active natural and synthetic products, 11 unnatural amino acids 12 and chiral auxiliaries for asymmetric synthesis. 13 The classical synthesis of b-amino alcohols involves the heating of epoxide with an excess of amines at elevated temperature.…”

Nucleoside Analogs as Anti-HBV Agents

“…While entecavir is an extremely potent anti-HBV agent, its enantiomer (31) was totally inactive [81,84]. The base modification with purine substitution is tolerable; the adenine analogue (32) retains significant activity, however the potency is about 30-40 folds lower [81].…”

Developments in Antiviral Drug Design, Discovery and Development in 2004

“…In a patient who had failed famciclovir, ganciclovir, foscarnet and lamivudine harboring the substitutions S78S/T, V173L, L180M, T184S and M204V in the HBV RT gene, T184G, I169T and S202I emerged after 76 weeks of entecavir therapy and resistance in vitro was highest with T184G and S202I added to the lamivudineresistant background [576]. A model of the HBV polymerase has been developed that is claimed to provide insight into the mechanistic basis for resistance to several nucleoside analogues, including entecavir [577] and the synthesis of 3'-deoxy analogues of entecavir has been published [578].…”