Conformational and NBO analysis of bicyclo[3.1.0] hexanes All roads lead to boats

SERGIO H. SZAJNMAN; JUAN B. RODRIGUEZ; MARGARITA VALLEJOS; SHEILA IRINA DE DIEGO SAADIA

Simposio; Humboldt Kolleg - Expanding the Frontiers of Science: A Transdiciplinary Approach; 2022

Humbold Foundation

Nucleosides and nucleotides are best known as the molecular building blocks of the DNA and RNA. These molecules bind and activate a number of receptors that have diverse and important signalling roles in the body. Nucleosides and nucleotides in which the ribose ring is replaced by a bicyclo[3.1.0]hexane result in versatile drug-like scaffolds to increase molecular recognition. Certainly, this concept was first introduced in nucleosides by Marquez et al. leading to conformationally locked nucleosides bearing superior pharmacological action.1,2 N-methano-carba-thymidine and S-methano-carba-thymidine arise as representative members of this family of conformationally restricted carbanucleosides.In an attempt to rationalize the tendency of bicyclo[3.1.0]hexane systems to adopt a boat-like conformers, we mapped the energy landscapes of the complete conformational space of these moieties. Therefore, we carried out an NBO analysis, which allowed us to rationalize the interactions present in the molecule that force molecule to assume this boat-like preferred conformation. These findings will undoubtedly be an important tool for designing new conformationally restricted nucleosides