Conformationally restricted Nucleocyclitols: a study into their conformational preferences and supramolecular architecture in the solid state

Abstract

With the intent of probing the feasibility of employing annulation as a tactic to engender axial rich conformations in nucleoside analogues, two adenine-derived, "conformationally restricted" nucleocylitols, 9 and 10, have been conceptualized as representatives of a hitherto unexplored class of nucleic acid base-cyclitol hybrids. A general synthetic strategy, with an inherent scope for diversification, allowed rapid functionalization of indane and tetralin to furnish 9 and 10 respectively in fair yield. Single-crystal X-ray diffraction analysis revealed that the two nucleocyclitols under study, though homologous, present completely dissimilar modes of molecular packing, marked, in particular, by the nature of involvement of the adenynyl NH₂ group in the supramolecular assembly. In addition, the crystal structures of 9 and 10 also exhibit two different conformations of the functionalized cyclohexane ring. Thus, while the six-membered carbocycle in cyclopenta-annulated 9 exists in the expected chair (C) conformation that in cyclohexaannulated 10, which crystallizes as a dihydrate, shows an unusual twist-boat (TB) conformation. From a close analysis of the ¹HNMR spectroscopic data recorded for 9 and 10 in CD₃OD, it was possible to put forth a putative explanation for the uncanny conformational preferences of crystalline 9 and 10.