Non-canonical nucleosides and proto-urea-RNA at the chemical origins of life

The work presented in this dissertation was aimed towards furthering our understanding of the chemical processes that gave rise to the emergence of life on Earth. Specifically, we provide new evidence to support the RNA World Hypothesis, which suggests that the first organisms were preceded by an era in which RNA molecules catalysed their own autonomous replication. To this end, the syntheses of certain prebiotically plausible pseudo-RNA nucleosides derived from Biuret and Triuret are reported. Remarkably, in addition to being hydrolytically stable, these planar H-bonded pseudobases exhibit unique base-pairing properties that mirror that of a UG wobble-base pair when coupled with guanine or inosine within an RNA duplex. Possible mechanisms for an evolutionary transition from such pseudobases to the canonical pyrimidines are discussed. In pursuit of further proto-RNA structures, prebiotically plausible routes to a number of extant methylated nucleobases, as well as the carbamoylated adenosine nucleosides N6-threonylcarbamoyl adenosine (t6A) and N6-glycinylcarbamoyl adenosine (g6A) are described. These nucleosides are universally conserved and present within the genome of the last universal common ancestor (LUCA), which together with their ease of synthesis, suggests that they might endure today as molecular fossils from our RNA-based progenitors. Preparation of the first nucleoside phosphoramidites for g6A and related structures were also established, thus allowing their incorporation into RNA strands and investigation of their theorised role in the origin of translation. Finally, a novel prebiotically plausible route to pyrimidine nucleosides is reported, as well as encouraging preliminary results towards the synthesis of a phosphoramidite building block of the 1-(isoxazol-3-yl)-3-ribosylurea precursor from that pathway