posted on 2017-03-07, 00:00authored byLukáš 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.