Chemoselective Multicomponent One-Pot Assembly of Purine Precursors in Water
Open accessAbstract
The recent development of a sequential, high-yielding route to activated pyrimidine nucleotides, under conditions thought to be prebiotic, is an encouraging step toward the greater goal of a plausible prebiotic pathway to RNA and the potential for an RNA world. However, this synthesis has led to a disparity in the methodology available for stepwise construction of the canonical pyrimidine and purine nucleotides. To address this problem, and further explore prebiotically accessible chemical systems, we have developed a high-yielding, aqueous, one-pot, multicomponent reaction that tethers masked-sugar moieties to prebiotically plausible purine precursors. A pH-dependent three-component reaction system has been discovered that utilizes key nucleotide synthons 2-aminooxazole and 5-aminoimidazoles, which allows the first divergent purine/pyrimidine synthesis to be proposed. Due to regiospecific aminoimidazole tethering, the pathway allows N9 purination only, thus suggesting the first prebiotically plausible mechanism for regiospecific N9 purination.
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TAPs is obtained in 'one pot' from three main components: glyceraldehyde, aminooxazole (AO, obtained from cyanamide and glycoaldehyde) and 5-aminoimidazole-4-carboxamide (AICA).
“This molecule is obtained in 'one pot' from three main components: glyceraldehyde, aminooxazole (AO, obtained from cyanamide and glycoaldehyde, cf. Figures 10 and 11) and 5-aminoimidazole-4carboxamide (AICA, c.f. Figure 11).”
From The Origin and Early Evolution of Life: Homochirality Emergence in Prebiotic Environments (2023) · cites this paper as Powner et al., 2010
The Results and Discussion (Glyceraldehyde; page unavailable) and Experimental Section (compound 24; page unavailable) show a one-pot reaction of glyceraldehyde, 2-aminooxazole, and AICA that produces a purine precursor. The cited passages do not establish the parenthetical claim that the 2-aminooxazole used here was obtained from cyanamide and glycolaldehyde; the cyanamide preparation described in the Experimental Section uses glyceraldehyde and yields a different aminooxazole. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA similar approach has been applied to the chemoselective assembly of purine nucleotide precursors.
“A similar approach has been applied to the chemoselective assembly of purine nucleotide precursors (Powner et al. 2010).”
From Protocells and RNA Self-Replication (2018) · cites this paper as Powner et al. 2010
Purine precursors or PNA nucleotides precursors were also obtained in racemic mixtures.
“Purine precursors or PNA nucleotides (Engelhart and Hud, 2010) precursors were also obtained in racemic mixtures.”
From The Origin and Early Evolution of Life: Homochirality Emergence in Prebiotic Environments (2023) · cites this paper as Powner et al., 2010
AICA was obtained by chemical rearrangement and hydrolysis of hydrogen cyanide tetramers (HCT).
“For instance, AICA was obtained by chemical rearrangement and hydrolysis of hydrogen cyanide tetramers (HCT).(Powner et al., 2010)”
From The Origin and Early Evolution of Life: Homochirality Emergence in Prebiotic Environments (2023) · cites this paper as Powner et al., 2010
Different combinations of aminooxazole, AICAs and glyceraldehyde or different aldehydes including glycoaldehyde or formaldehyde yielded different potential purine precursors.
“Different combinations of aminooxazole, AICAs and glyceraldehyde or different aldehydes including glycoaldehyde of formaldehyde yielded different potential purine precursors.(Powner et al., 2010)”
From The Origin and Early Evolution of Life: Homochirality Emergence in Prebiotic Environments (2023) · cites this paper as Powner et al., 2010
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- Authors
- Powner, M. W., Sutherland, J. D., & Szostak, J. W.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Powner, Matthew W.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-11-02
- Volume
- 132
- Issue
- 46
- Pages
- 16677-16688
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC2984373
- OpenAlex
- W1992304492
- Cited by
- 150
- References
- 6
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 10 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 15 · 2016: 8 · 2015: 7 · 2014: 19 · 2013: 17 · 2012: 15
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American Chemical Society (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Physical Sciences › Chemistry › Organic Chemistry › Multicomponent Synthesis of Heterocycles
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- purine nucleotide synthesis, prebiotic chemistry, multicomponent reactions, one-pot synthesis, aqueous synthesis, 2-aminooxazole, pyrimidine nucleotides, RNA world
- MeSH terms
- Hydrogen-Ion Concentration, Purines, Pyrimidines, Water, Molecular Structure
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