Among the many prebiotic phosphorylation chemistries investigated, diamidophosphate (DAP) has shown promising potential for nucleoside phosphorylation. Herein, we show that DAP's phosphorylation capability is enhanced significantly (up to 90%) in wet-dry cycles by a range of prebiotically plausible pHs (6-10) and temperatures (up to 80 °C) in the presence of additives such as formamide, cyanamide, urea, guanidine, 2-aminoimidazole, and hydantoin. For ribonucleosides, the main products are the 2',3'-cyclic phosphates along with the corresponding 2'- and 3'-phosphates, while deoxyribonucleosides form 5'- and 3'-phosphates, the ratios of which are affected by cycles and the presence and nature of the additives.
View Article and Find Full Text PDFOrg Biomol Chem
May 2023
Chiral Phosphoric Acids (CPAs) are a highly versatile class of Brønsted acid organocatalysts that have witnessed a surge in their use in asymmetric synthesis in recent years. Various new protocols, including photoredox, atroposelective, and multicomponent reactions, have been developed to expand the range of applications for these catalysts. This review specifically examines the use of standalone chiral phosphoric acids as organocatalysts in asymmetric syntheses from 2018 to 2022.
View Article and Find Full Text PDFPolymerization of nucleic acids in biology utilizes 5'-nucleoside triphosphates (NTPs) as substrates. The prebiotic availability of NTPs has been unresolved and other derivatives of nucleoside-monophosphates (NMPs) have been studied. However, this latter approach necessitates a change in chemistries when transitioning to biology.
View Article and Find Full Text PDFRecent demonstrations of RNA-DNA chimeras (RDNA) enabling RNA and DNA replication, coupled with prebiotic co-synthesis of deoxyribo- and ribo-nucleotides, have resurrected the hypothesis of co-emergence of RNA and DNA. As further support, we show that diamidophosphate (DAP) with 2-aminoimidazole (amido)phosphorylates and oligomerizes deoxynucleosides to form DNA-under conditions similar to those of ribonucleosides. The pyrimidine deoxynucleoside 5'-O-amidophosphates are formed in good (≈60 %) yields.
View Article and Find Full Text PDFRNA-catalyzed RNA ligation is widely believed to be a key reaction for primordial biology. However, since typical chemical routes towards activating RNA substrates are incompatible with ribozyme catalysis, it remains unclear how prebiotic systems generated and sustained pools of activated building blocks needed to form increasingly larger and complex RNA. Herein, we demonstrate in situ activation of RNA substrates under reaction conditions amenable to catalysis by the hairpin ribozyme.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2019
Phosphorylation of (pre)biotically relevant molecules in aqueous medium has recently been demonstrated using water-soluble diamidophosphate (DAP). Questions arise relating to the prebiotic availability of DAP and other amidophosphosphorus species on the early earth. Herein, we demonstrate that DAP and other amino-derivatives of phosphates/phosphite are generated when Fe P (proxy for mineral schreibersite), condensed phosphates, and reduced oxidation state phosphorus compounds, which could have been available on early earth, are exposed to aqueous ammonia solutions.
View Article and Find Full Text PDFWe used our recently proposed acidity-basicity interplay (ABI) model (Chem. Sci., 2018, 9, 4402) and the Jorgensen secondary interactions hypothesis (JSIH) to rationalise the experimentally observed trends in the formation constants of doubly and triply H-bonded systems with -NHO[double bond, length as m-dash]C- and -NHN- interactions.
View Article and Find Full Text PDFAmides dimerise more strongly than imides despite their lower acidity. Such an unexpected result has been rationalised in terms of the Jorgensen Secondary Interactions Hypothesis (JSIH) that involves the spectator (C[double bond, length as m-dash]O) and H-bonded (C[double bond, length as m-dash]O) carbonyl groups in imides. Notwithstanding the considerable body of experimental and theoretical evidence supporting the JSIH, there are some computational studies which suggest that there might be other relevant intermolecular interactions than those considered in this model.
View Article and Find Full Text PDFThioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis of bifunctional thioureas with a chiral moiety that include either a trifluoromethyl or methyl group.
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