3-Substituted Purines

Abstract

As the central repository of biological information and ultimate mediator of all processes underlying the activities of living organisms, nucleic acids are the sine qua non for life as we know it. Biological research over the past century and more has revealed much of the structure and function of nucleic acids, revealing in turn how life begins, changes, reproduces, and ends. We glimpse how life has become what it is and perhaps what it may become. This work seeks to understand the ramifications of altering a single nitrogen of the purine nucleoside components of nucleic acids. As will be shown, purine analogs lacking the N3 nitrogen have altered interactions with proteins, water, and other molecules. Replacement of this nitrogen with a C-H, C-CH3, or C-CH2OH functionality impacts the structure and biological interactions of a DNA duplex containing these alterations in ways not entirely foreseen when this work began over ten years ago. The synthetic effort needed to obtain purine nucleosides containing each of these modifications is significant. Along the way, new methodologies applicable both to the synthesis of purine analogs and natural purine nucleosides are described.