Enantioselective syntheses of carbocyclic nuleosides 5'-homocarbovir, epi-4'-homocarbovir and their cyclopropylamine analogs using facially selective Pd-mediated allylations

Tardibono, Lawrence P; Miller, Marvin J; Balzarini, Jan

doi:10.1016/j.tet.2010.11.097

Enantioselective syntheses of carbocyclic nuleosides 5'-homocarbovir, epi-4'-homocarbovir and their cyclopropylamine analogs using facially selective Pd-mediated allylations

Author:

Tardibono, Lawrence P

Miller, Marvin J ; Balzarini, Jan

Keywords:

Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, ANTIVIRAL ACTIVITY, POLYOXIN-C, ABACAVIR, AMINOCYCLOPENTENOLS, SUBSTRATE, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, Organic Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

Carbocyclic nucleosides (-)-5'-homocarbovir and (+)-epi-4'-homocarbovir were prepared from an acylnitroso-derived hetero Diels-Alder cycloadduct. A kinetic enzymatic resolution generated an enantiopure aminocyclopentenol and Pd(0)-mediated decarboxylative allylations of allyl 2,2,2-trifluoroethyl malonates were used to install the 4'-hydroxyethyl groups. Late stage derivatization gave access to the cyclopropylamine congenors, (-)-5'-homoabacavir and (+)-epi-4'-homoabacavir. All carbonucleoside target molecules were evaluated for antiviral activity.