Diastereoselective Flexible Synthesis of Carbocyclic C‑Nucleosides
journal contributionposted on 2017-03-07, 00:00 authored by Lukáš Maier, Prashant Khirsariya, Ondřej Hylse, Santosh Kumar Adla, Lenka Černová, Michal Poljak, Soňa Krajčovičová, Erik Weis, Stanislav Drápela, Karel Souček, Kamil Paruch
Carbocyclic C-nucleosides are quite rare. Our route enables flexible preparation of three classes of these nucleoside analogs from common precursors–properly substituted cyclopentanones, which can be prepared racemic (in six steps) or optically pure (in ten steps) from inexpensive norbornadiene. The methodology allows flexible manipulation of individual positions around the cyclopentane ring, namely highly diastereoselective installation of carbo- and heterocyclic substituents at position 1′, orthogonal functionalization of position 5′, and efficient inversion of stereochemistry at position 2′. Newly prepared carbocyclic C-analog of tubercidine, profiled in MCF7 (breast cancer) and HFF1 (human foreskin fibroblasts) cell cultures, is less potent than tubercidine itself, but more selectively toxic toward the tumorigenic cells.