One‐Pot TiO₂‐Catalyzed Synthesis of Nucleic Bases and Acyclonucleosides from Formamide: Implications for the Origin of Life

Abstract

A novel one-pot TiO2-catalyzed synthesis of nucleobases and acyclonucleosides from formamide is reported. Since formamide can be formed under prebiotic conditions, these reactions have implications for the origin of life. While a number of purine derivatives have been found as products of non-TiO2-catalyzed reactions, important compounds that would not otherwise occur (namely, thymine, 5-hydroxymethyluracil, and acyclonucleosides) are formed in acceptable yields by TiO2-catalyzed reactions. Moreover, TiO2 selectively affects the rates of degradation of nucleobases, as single units and when embedded in polynucleotides.

Very Efficient Template/Primer-Independent DNA Synthesis by Thermophilic DNA Polymerase in the Presence of a Thermophilic Restriction Endonuclease

“…It can be expected that when several restriction enzymes are mixed, the DNA involving more genetic information might be obtained from RE-pol DNA synthesis (under study). Our findings shed a new light on the template/ primer-independent synthesis of nucleic acids as a necessary step of prebiological evolution (29). The findings suggest that the digestion of nucleic acids may play an important role in the evolution of genetic material for procreating the diversification of genetic information on the early earth.…”

Formamide and the origin of life

“…Recent findings suggest a solution [28], for conditions probably different from those that supposedly characterized prebiotic processes (namely: simplicity, robustness and availability of abundant precursors). Formamide chemistry allows the formation of acyclonucleosides in non-demanding conditions [29]. As for the next step toward (pre)genetic complexity, formamide chemistry also carries on phosphorylation of nucleosides [30].…”

“…In 2003 thymine was synthesized from H 2 NCHO in the presence of titanium dioxide (TiO 2 ) [29]. In this case three novel purine acyclonucleosides, in which the heterocyclic base is bonded to a sugar-like side-chain in the N(9)-position, were obtained in addition to 5-hydroxymethyl uracil (5-HMU).…”

“…The use of amino pentose-oxazolines as intermediates in the synthesis of nucleoside derivatives is a well-known practice in medicinal chemistry [98]. These procedures generally require lengthy optimization of experimental conditions and efficient purification techniques of the various intermediates [98]; 2) different purine acyclonucleosides have been synthesized from H 2 NCHO and TiO 2 by a one-pot domino process [29] including the N -formylation of the nucleobase at the N(9)-position followed by a formose condensation. In this process, the sugar side-chain grew adding single carbon units of formaldehyde.…”

“…Formamide condensation affords all the necessary nucleic bases and acyclic nucleosides [26,27,29], allows the efficient phosphorylation of nucleosides in every possible position of ribose [30], also yielding cyclic phosphate forms. In water, purine 3 ,5 cyclic nucleotides polymerize to oligomers [31] which may non-enzymatically ligate affording long RNA molecules [129,130].…”