Selective Derivatization and Sequestration of Ribose from a Prebiotic Mix

Observations regarding the catalytic potential of RNA and the role of RNA in biology have formed
the basis for the “RNA world” hypothesis, which suggests that a genetic system based on self-replicating
polyribonucleotides preceded modern biology. However, attempts to devise a realistic prebiotic synthesis
of nucleic acids from simple starting materials have been plagued by problems of poor chemical selectivity,
lack of stereo- and regiospecificity, and similar rates of formation and degradation of some of the key
intermediates. For example, ribose would have been only a small component of a highly complex mix of
sugars resulting from the condensation of formaldehyde in a prebiotic world. In addition, ribose is more
reactive and degrades more rapidly compared with most other monosaccharides. This study demonstrates
an approach for the preferential sequestration of ribose relative to other sugars that takes advantage of its
greater reactivity. Cyanamide reacts especially rapidly with ribose to form a stable bicyclic adduct. This
product crystallizes spontaneously in aqueous solution, whereas the corresponding products derived from
threose, galactose, glucose, mannose, and each of the other pentoses do not. Furthermore, when employing
a racemic mixture of d- and l-ribose, enantiomerically twinned crystals are formed that contain discrete
homochiral domains.