DIVERSITY-ORIENTED SYNTHESIS FROM CARBOHYDRATES AND NUCLEOSIDES

The aim of Diversity-Oriented Synthesis (DOS) is the design of a series of efficient chemical transformations (limited number of synthetic steps, reliable, high yielding) that eventually would lead to a large set of structurally complex and diverse molecules from a common synthetic precursor..

In our group, starting from simple carbohydrates, we have been able to obtain a cyclic enamine which has been used as a versatile common synthetic precursor in the synthesis of a series of sugar and nucleoside derivatives of high structural complexity characterized by the presence of unusual fused-polycycles on their structures.

Our library of compounds is now under evaluation against a broad panel of biologically relevant targets. Up to now, we have identified a first series of tricyclic nucleosides that are significant and selective inhibitors of HIV-1 replication and a second series of bicyclic nucleosides with a remarkable inhibitory activity against Plasmodium Falciparum at the sub-micromolar range.

Relevant publications:

• 2011 - Bonache, M. C.; Cordeiro, A.; Quesada, E.; Vanstreels, E.; Daelemans, D.; Camarasa, M. J.; Balzarini, J.; San Félix, A.

  Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides. Antivir. Res., 2011, 92, 37-44.

• 2009 - Bonache, M. C.; Cordeiro, A.; Quesada, E.; Camarasa, M. J.; Jimeno, M. L.; San-Félix, A.

  One-pot synthesis of polycyclic nucleosides with unusual molecular skeletons J. Org. Chem. 2009, 74, 9071-9081.

• 2006 - Cordeiro, A; Quesada, E; Bonache, M. C; Velázquez, S; Camarasa, M. J; San-Félix, A.

  A cyclic enamine derived from 1,2-O-isopropylidene-α-D-xylofuranose as a novel carbohydrate intermediate to achieve skeletal diversity. J. Org. Chem. 2006, 71, 7224-7235.