Ashe, Kathryn; (2018) Studies towards the prebiotic synthesis of nucleotides and amino acids. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Understanding how life on Earth might have started is the major goal of prebiotic chemistry. The universal nature of extant life, with integrated informational, catalytic and compartment-forming systems, suggests a common chemical origin. Comprehensive studies of the feasible routes towards the biomolecules necessary for life will refine our knowledge of the prebiotic chemistry that lead to life. The integration of genetic information and proteins in the central dogma of molecular biology indicates the importance of evaluating the prebiotic synthesis of amino acids and peptides. Following the principles of prebiotic systems chemistry, ideally this should take place under similar conditions established for other prebiotically plausible networks that lead to other key class of metabolite using common reagents. Here we focus on resolving the pH incompatibility of nucleotide (pH <7) and amino acid synthesis (by Strecker reaction of ammonium cyanide and aldehydes, pH >9). Introducing DAP – a reagent previously implicated in various areas of prebiotic chemistry – into the Strecker reaction enables the synthesis of N-phosphoroaminonitriles at pH 7, and is highly selective for proteinogenic over non-proteinogenic amino acid precursors. Derivatisation of the products of this phosphoro-Strecker reaction provides a handle for further reaction and possible oligomerisation. Phosphate is used as a universal energy currency in extant life, notably in amino acid activation in protein synthesis, so the formation of a phosphorylated amino acid derivative in this work is particularly interesting. The ubiquity of RNA in modern biochemistry and RNA’s dual functionality (genotypic and phenotypic) makes RNA a strong contender for the first biopolymer. We also present an account of our results exploring: the replacement of phosphate with borate in the stereochemical rearrangement of 2′,2-anhydropyrimidines and 2′,8-anhydropurines; the formation of a glycosidic bond between acetylated ribose derivatives (from the UV irradiation of unwanted α-pyrimidine by-products) and purine nucleobases; and a stereospecific reduction of 5′,8-cyclopurines.

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