Unravelling the regio- and stereoselective synthesis of bicyclic N,O-nucleoside analogues within the molecular electron density theory perspective.

ABSTRACT: The [3?+?2] cycloaddition (32CA) reactions of 1-pyrroline-1-oxide with N-vinyl nucleobases leading to bicyclic N,O nucleoside analogues have been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These non-polar zwitterionic type 32CA reactions take place through a one-step mechanism with minimal global electron density transfer (GEDT) at the TSs and the exo/ortho approach mode as the energetically favoured reaction path. The 32CA reactions of N-vinyl nucleobases with thymine and cytosine substituents respectively show the activation enthalpies of 15.2 and 12.5 kcal mol^-1 in toluene. The reactions are irreversible due to strong exothermic character of -?35.4--?26.4 kcal mol^-1 in toluene. The bonding evolution theory (BET) study suggests that these 32CA reactions take place through the coupling of pseudoradical centres with earlier C-C bond formation and the formation of new C-C and C-O covalent bonds has not been started in the TSs. Non-covalent interactions (NCI) are predicted at the TSs from the visualization of NCI gradient isosurfaces.

SUBMITTER: Acharjee N 

PROVIDER: S-EPMC7315015 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature