Pyrimidine

Last updated
Pyrimidine
Pyrimidine 2D aromatic full.svg
Pyrimidine 2D numbers.svg
Pyrimidine-3D-balls-2.png
Pyrimidine-3D-spacefill.png
Names
Preferred IUPAC name
Pyrimidine [1]
Systematic IUPAC name
1,3-Diazabenzene
Other names
1,3-Diazine
m-Diazine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.479 OOjs UI icon edit-ltr-progressive.svg
KEGG
MeSH pyrimidine
PubChem CID
UNII
  • InChI=1S/C4H4N2/c1-2-5-4-6-3-1/h1-4H Yes check.svgY
    Key: CZPWVGJYEJSRLH-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C4H4N2/c1-2-5-4-6-3-1/h1-4H
    Key: CZPWVGJYEJSRLH-UHFFFAOYAT
  • n1cnccc1
Properties
C4H4N2
Molar mass 80.088 g mol−1
Density 1.016 g cm−3
Melting point 20 to 22 °C (68 to 72 °F; 293 to 295 K)
Boiling point 123 to 124 °C (253 to 255 °F; 396 to 397 K)
Miscible (25°C)
Acidity (pKa)1.10 [2] (protonated pyrimidine)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Pyrimidine (C4H4N2; /pɪˈrɪ.mɪˌdiːn,paɪˈrɪ.mɪˌdiːn/ ) is an aromatic, heterocyclic, organic compound similar to pyridine (C5H5N). [3] One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. [4] : 250  The other diazines are pyrazine (nitrogen atoms at the 1 and 4 positions) and pyridazine (nitrogen atoms at the 1 and 2 positions).

Contents

In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U).

Occurrence and history

Pinner's 1885 structure for pyrimidine PinnerPyrimidin.png
Pinner's 1885 structure for pyrimidine

The pyrimidine ring system has wide occurrence in nature [5] as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug, zidovudine. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879, [5] when Grimaux reported the preparation of barbituric acid from urea and malonic acid in the presence of phosphorus oxychloride. [6] The systematic study of pyrimidines began [7] in 1884 with Pinner, [8] who synthesized derivatives by condensing ethyl acetoacetate with amidines. Pinner first proposed the name “pyrimidin” in 1885. [9] The parent compound was first prepared by Gabriel and Colman in 1900, [10] [11] by conversion of barbituric acid to 2,4,6-trichloropyrimidine followed by reduction using zinc dust in hot water.

Nomenclature

The nomenclature of pyrimidines is straightforward. However, like other heterocyclics, tautomeric hydroxyl groups yield complications since they exist primarily in the cyclic amide form. For example, 2-hydroxypyrimidine is more properly named 2-pyrimidone. A partial list of trivial names of various pyrimidines exists. [12] : 5–6 

Physical properties

Physical properties are shown in the data box. A more extensive discussion, including spectra, can be found in Brown et al. [12] : 242–244 

Chemical properties

Per the classification by Albert [13] : 56–62  six-membered heterocycles can be described as π-deficient. Substitution by electronegative groups or additional nitrogen atoms in the ring significantly increase the π-deficiency. These effects also decrease the basicity. [13] : 437–439 

Like pyridines, in pyrimidines the π-electron density is decreased to an even greater extent. Therefore, electrophilic aromatic substitution is more difficult while nucleophilic aromatic substitution is facilitated. An example of the last reaction type is the displacement of the amino group in 2-aminopyrimidine by chlorine [14] and its reverse. [15]

Electron lone pair availability (basicity) is decreased compared to pyridine. Compared to pyridine, N-alkylation and N-oxidation are more difficult. The pKa value for protonated pyrimidine is 1.23 compared to 5.30 for pyridine. Protonation and other electrophilic additions will occur at only one nitrogen due to further deactivation by the second nitrogen. [4] : 250  The 2-, 4-, and 6- positions on the pyrimidine ring are electron deficient analogous to those in pyridine and nitro- and dinitrobenzene. The 5-position is less electron deficient and substituents there are quite stable. However, electrophilic substitution is relatively facile at the 5-position, including nitration and halogenation. [12] : 4–8 

Reduction in resonance stabilization of pyrimidines may lead to addition and ring cleavage reactions rather than substitutions. One such manifestation is observed in the Dimroth rearrangement.

Pyrimidine is also found in meteorites, but scientists still do not know its origin. Pyrimidine also photolytically decomposes into uracil under ultraviolet light. [16]

Synthesis

As is often the case with parent heterocyclic ring systems, the synthesis of pyrimidine is not that common and is usually performed by removing functional groups from derivatives. Primary syntheses in quantity involving formamide have been reported. [12] : 241–242 

As a class, pyrimidines are typically synthesized by the principal synthesis involving cyclization of β-dicarbonyl compounds with N–C–N compounds. Reaction of the former with amidines to give 2-substituted pyrimidines, with urea to give 2-pyrimidinones, and guanidines to give 2-aminopyrimidines are typical. [12] : 149–239 

Pyrimidines can be prepared via the Biginelli reaction and other multicomponent reactions. [17] Many other methods rely on condensation of carbonyls with diamines for instance the synthesis of 2-thio-6-methyluracil from thiourea and ethyl acetoacetate [18] or the synthesis of 4-methylpyrimidine with 4,4-dimethoxy-2-butanone and formamide. [19]

A novel method is by reaction of N-vinyl and N-aryl amides with carbonitriles under electrophilic activation of the amide with 2-chloro-pyridine and trifluoromethanesulfonic anhydride: [20]

PyrimidineSynthAmideCarbonitrile.png

Reactions

Because of the decreased basicity compared to pyridine, electrophilic substitution of pyrimidine is less facile. Protonation or alkylation typically takes place at only one of the ring nitrogen atoms. Mono-N-oxidation occurs by reaction with peracids. [4] : 253–254 

Electrophilic C-substitution of pyrimidine occurs at the 5-position, the least electron-deficient. Nitration, nitrosation, azo coupling, halogenation, sulfonation, formylation, hydroxymethylation, and aminomethylation have been observed with substituted pyrimidines. [12] : 9–13 

Nucleophilic C-substitution should be facilitated at the 2-, 4-, and 6-positions but there are only a few examples. Amination and hydroxylation have been observed for substituted pyrimidines. Reactions with Grignard or alkyllithium reagents yield 4-alkyl- or 4-aryl pyrimidine after aromatization. [12] : 14–15 

Free radical attack has been observed for pyrimidine and photochemical reactions have been observed for substituted pyrimidines. [12] : 15–16  Pyrimidine can be hydrogenated to give tetrahydropyrimidine. [12] : 17 

Derivatives

Pyrimidine derivatives
FormulaNameStructureC2C4C5C6
C4H5N3O cytosine Pyrimidin num.svg =O–NH2–H–H
C4H4N2O2 uracil =O=O–H–H
C4H3FN2O2 fluorouracil =O=O–F–H
C5H6N2O2 thymine =O=O–CH3–H
C4H4N2O3 barbituric acid =O=O–H=O
C5H4N2O4 orotic acid =O=O–H-COOH

Nucleotides

The pyrimidine nitrogen bases found in DNA and RNA. Blausen 0324 DNA Pyrimidines.png
The pyrimidine nitrogen bases found in DNA and RNA.

Three nucleobases found in nucleic acids, cytosine (C), thymine (T), and uracil (U), are pyrimidine derivatives:

Chemical structure of cytosine Cytosine chemical structure.png
Chemical structure of cytosine
Chemical structure of thymine Thymine chemical structure.png
Chemical structure of thymine
Chemical structure of uracil Uracil chemical structure.png
Chemical structure of uracil
Cytosine (C)
Thymine (T)
Uracil (U)

In DNA and RNA, these bases form hydrogen bonds with their complementary purines. Thus, in DNA, the purines adenine (A) and guanine (G) pair up with the pyrimidines thymine (T) and cytosine (C), respectively.

In RNA, the complement of adenine (A) is uracil (U) instead of thymine (T), so the pairs that form are adenine:uracil and guanine:cytosine.

Very rarely, thymine can appear in RNA, or uracil in DNA, but when the other three major pyrimidine bases are represented, some minor pyrimidine bases can also occur in nucleic acids. These minor pyrimidines are usually methylated versions of major ones and are postulated to have regulatory functions. [21]

These hydrogen bonding modes are for classical Watson–Crick base pairing. Other hydrogen bonding modes ("wobble pairings") are available in both DNA and RNA, although the additional 2′-hydroxyl group of RNA expands the configurations, through which RNA can form hydrogen bonds. [22]

Theoretical aspects

In March 2015, NASA Ames scientists reported that, for the first time, complex DNA and RNA organic compounds of life, including uracil, cytosine and thymine, have been formed in the laboratory under outer space conditions, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar dust and gas clouds. [23] [24] [25]

Prebiotic synthesis of pyrimidine nucleotides

In order to understand how life arose, knowledge is required of the chemical pathways that permit formation of the key building blocks of life under plausible prebiotic conditions. The RNA world hypothesis holds that in the primordial soup there existed free-floating ribonucleotides, the fundamental molecules that combine in series to form RNA. Complex molecules such as RNA must have emerged from relatively small molecules whose reactivity was governed by physico-chemical processes. RNA is composed of pyrimidine and purine nucleotides, both of which are necessary for reliable information transfer, and thus natural selection and Darwinian evolution. Becker et al. showed how pyrimidine nucleosides can be synthesized from small molecules and ribose, driven solely by wet-dry cycles. [26] Purine nucleosides can be synthesized by a similar pathway. 5’-mono-and diphosphates also form selectively from phosphate-containing minerals, allowing concurrent formation of polyribonucleotides with both the pyrimidine and purine bases. Thus a reaction network towards the pyrimidine and purine RNA building blocks can be established starting from simple atmospheric or volcanic molecules.

See also

Related Research Articles

<span class="mw-page-title-main">Cytosine</span> Chemical compound in nucleic acids

Cytosine is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine. It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached. The nucleoside of cytosine is cytidine. In Watson-Crick base pairing, it forms three hydrogen bonds with guanine.

<span class="mw-page-title-main">Guanine</span> Chemical compound of DNA and RNA

Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine. In DNA, guanine is paired with cytosine. The guanine nucleoside is called guanosine.

<span class="mw-page-title-main">Heterocyclic compound</span> Molecule with one or more rings composed of different elements

A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.

<span class="mw-page-title-main">Nucleotide</span> Biological molecules that form the building blocks of nucleic acids

Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver.

<span class="mw-page-title-main">Purine</span> Heterocyclic aromatic organic compound

Purine is a heterocyclic aromatic organic compound that consists of two rings fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines and their tautomers. They are the most widely occurring nitrogen-containing heterocycles in nature.

<span class="mw-page-title-main">Pyridine</span> Heterocyclic aromatic organic compound

Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a distinctive, unpleasant fish-like smell. Pyridine is colorless, but older or impure samples can appear yellow, due to the formation of extended, unsaturated polymeric chains, which show significant electrical conductivity. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Historically, pyridine was produced from coal tar. As of 2016, it is synthesized on the scale of about 20,000 tons per year worldwide.

<span class="mw-page-title-main">Adenine</span> Chemical compound in DNA and RNA

Adenine is a nucleobase. It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivatives have a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate (ATP) and the cofactors nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD) and Coenzyme A. It also has functions in protein synthesis and as a chemical component of DNA and RNA. The shape of adenine is complementary to either thymine in DNA or uracil in RNA.

<span class="mw-page-title-main">Uracil</span> Chemical compound of RNA

Uracil is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine (T). Uracil is a demethylated form of thymine.

<span class="mw-page-title-main">Thymine</span> Chemical compound of DNA

Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. In RNA, thymine is replaced by the nucleobase uracil. Thymine was first isolated in 1893 by Albrecht Kossel and Albert Neumann from calf thymus glands, hence its name.

<span class="mw-page-title-main">Nucleobase</span> Nitrogen-containing biological compounds that form nucleosides

Nucleobases, also known as nitrogenous bases or often simply bases, are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called primary or canonical. They function as the fundamental units of the genetic code, with the bases A, G, C, and T being found in DNA while A, G, C, and U are found in RNA. Thymine and uracil are distinguished by merely the presence or absence of a methyl group on the fifth carbon (C5) of these heterocyclic six-membered rings. In addition, some viruses have aminoadenine (Z) instead of adenine. It differs in having an extra amine group, creating a more stable bond to thymine.

<span class="mw-page-title-main">Ribonucleotide</span> Nucleotide containing ribose as its pentose component

In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.

<span class="mw-page-title-main">Imidazole</span> Chemical compound

Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non-adjacent nitrogen atoms in meta-substitution.

Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS. The thiazole ring is notable as a component of the vitamin thiamine (B1).

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.

<span class="mw-page-title-main">Heterocyclic amine</span> Any heterocyclic compound having at least one nitrogen heteroatom

Heterocyclic amines, also sometimes referred to as HCAs, are chemical compounds containing at least one heterocyclic ring, which by definition has atoms of at least two different elements, as well as at least one amine (nitrogen-containing) group. Typically it is a nitrogen atom of an amine group that also makes the ring heterocyclic, though compounds exist in which this is not the case. The biological functions of heterocyclic amines vary, including vitamins and carcinogens. Carcinogenic heterocyclic amines are created by high temperature cooking of meat and smoking of plant matter like tobacco. Some well known heterocyclic amines are niacin, nicotine, and the nucleobases that encode genetic information in DNA.

<span class="mw-page-title-main">Nucleic acid analogue</span> Compound analogous to naturally occurring RNA and DNA

Nucleic acid analogues are compounds which are analogous to naturally occurring RNA and DNA, used in medicine and in molecular biology research. Nucleic acids are chains of nucleotides, which are composed of three parts: a phosphate backbone, a pentose sugar, either ribose or deoxyribose, and one of four nucleobases. An analogue may have any of these altered. Typically the analogue nucleobases confer, among other things, different base pairing and base stacking properties. Examples include universal bases, which can pair with all four canonical bases, and phosphate-sugar backbone analogues such as PNA, which affect the properties of the chain . Nucleic acid analogues are also called Xeno Nucleic Acid and represent one of the main pillars of xenobiology, the design of new-to-nature forms of life based on alternative biochemistries.

<span class="mw-page-title-main">Gould–Jacobs reaction</span>

The Gould–Jacobs reaction is an organic synthesis for the preparation of quinolines and 4‐hydroxyquinoline derivatives. The Gould-Jacobs reaction is a series of reactions. The series of reactions begins with the condensation/substitution of an aniline with alkoxy methylenemalonic ester or acyl malonic ester, producing anilidomethylenemalonic ester. Then through a 6 electron cyclization process, 4-hydroxy-3-carboalkoxyquinoline is formed, which exist mostly in the 4-oxo form. Saponification results in the formation of an acid. This step is followed by decarboxylation to give 4-hydroxyquinoline. The Gould-Jacobs reaction is effective for anilines with electron‐donating groups at the meta‐position.

<span class="mw-page-title-main">Indole</span> Organic compound with an intense fecal odor

Indole is an aromatic heterocyclic organic compound with the formula C8H7N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore formation, plasmid stability, resistance to drugs, biofilm formation, and virulence. The amino acid tryptophan is an indole derivative and the precursor of the neurotransmitter serotonin.

<span class="mw-page-title-main">Nucleic acid structure</span> Biomolecular structure of nucleic acids such as DNA and RNA

Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary, and quaternary.

Synthesis of nucleosides involves the coupling of a nucleophilic, heterocyclic base with an electrophilic sugar. The silyl-Hilbert-Johnson reaction, which employs silylated heterocyclic bases and electrophilic sugar derivatives in the presence of a Lewis acid, is the most common method for forming nucleosides in this manner.

References

  1. ↑ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 141. doi:10.1039/9781849733069-FP001. ISBN   978-0-85404-182-4.
  2. ↑ Brown, H. C.; et al. (1955). Baude, E. A.; F. C., Nachod (eds.). Determination of Organic Structures by Physical Methods. New York, NY: Academic Press.
  3. ↑ Gilchrist, Thomas Lonsdale (1997). Heterocyclic chemistry. New York: Longman. ISBN   978-0-582-27843-1.
  4. 1 2 3 Joule, John A.; Mills, Keith, eds. (2010). Heterocyclic Chemistry (5th ed.). Oxford: Wiley. ISBN   978-1-405-13300-5.
  5. 1 2 Lagoja, Irene M. (2005). "Pyrimidine as Constituent of Natural Biologically Active Compounds" (PDF). Chemistry and Biodiversity. 2 (1): 1–50. doi:10.1002/cbdv.200490173. PMID   17191918. S2CID   9942715.
  6. ↑ Grimaux, E. (1879). "Synthèse des dérivés uriques de la série de l'alloxane" [Synthesis of urea derivatives of the alloxan series]. Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences. 88: 85–87. Lock-green.svg
  7. ↑ Kenner, G. W.; Todd, Alexander (1957). Elderfield, R.C. (ed.). Heterocyclic Compounds. Vol. 6. New York: Wiley. p. 235.
  8. ↑ Pinner, A. (1884). "Ueber die Einwirkung von Acetessigäther auf die Amidine" [On the effect of acetylacetonate ester on amidines]. Berichte der Deutschen Chemischen Gesellschaft . A17 (2): 2519–2520. doi:10.1002/cber.188401702173. Lock-green.svg
  9. ↑ Pinner, A. (1885). "Ueber die Einwirkung von Acetessigäther auf die Amidine. Pyrimidin" [On the effect of acetylacetonate ester on amidines. Pyrimidine]. Berichte der Deutschen Chemischen Gesellschaft . A18: 759–760. doi:10.1002/cber.188501801161. Lock-green.svg
  10. ↑ Gabriel, S. (1900). "Pyrimidin aus Barbitursäure" [Pyrimidine from barbituric acid]. Berichte der Deutschen Chemischen Gesellschaft . A33 (3): 3666–3668. doi:10.1002/cber.190003303173. Lock-green.svg
  11. ↑ Lythgoe, B.; Rayner, L. S. (1951). "Substitution Reactions of Pyrimidine and its 2- and 4-Phenyl Derivatives". Journal of the Chemical Society . 1951: 2323–2329. doi:10.1039/JR9510002323.
  12. 1 2 3 4 5 6 7 8 9 Brown, D. J.; Evans, R. F.; Cowden, W. B.; Fenn, M. D. (1994). The Pyrimidines. New York, NY: John Wiley & Sons. ISBN   978-0-471-50656-0.
  13. 1 2 Albert, Adrien (1968). Heterocyclic Chemistry, an Introduction. London: Athlone Press.
  14. ↑ Kogon, Irving C.; Minin, Ronald; Overberger, C. G. "2-Chloropyrimidine". Organic Syntheses . 35: 34. doi: 10.15227/orgsyn.035.0034 .; Collective Volume, vol. 4, p. 182
  15. ↑ Overberger, C. G.; Kogon, Irving C.; Minin, Ronald. "2-(Dimethylamino)pyrimidine". Organic Syntheses . 35: 58. doi: 10.15227/orgsyn.035.0058 .; Collective Volume, vol. 4, p. 336
  16. ↑ Nuevo, M.; Milam, S. N.; Sandford, S. A.; Elsila, J. E.; Dworkin, J. P. (2009). "Formation of uracil from the ultraviolet photo-irradiation of pyrimidine in pure H2O ices". Astrobiology. 9 (7): 683–695. Bibcode:2009AsBio...9..683N. doi:10.1089/ast.2008.0324. PMID   19778279.
  17. ↑ Anjirwala, Sharmil N.; Parmar, Parnas S.; Patel, Saurabh K. (28 October 2022). "Synthetic protocols for non-fused pyrimidines". Synthetic Communications: 1–43. doi:10.1080/00397911.2022.2137682.
  18. ↑ Foster, H. M.; Snyder, H. R. "4-Methyl-6-hydroxypyrimidine". Organic Syntheses . 35: 80. doi: 10.15227/orgsyn.035.0080 .; Collective Volume, vol. 4, p. 638
  19. ↑ Bredereck, H. "4-methylpyrimidine". Organic Syntheses . 43: 77. doi: 10.15227/orgsyn.043.0077 .; Collective Volume, vol. 5, p. 794
  20. ↑ Movassaghi, Mohammad; Hill, Matthew D. (2006). "Single-Step Synthesis of Pyrimidine Derivatives". J. Am. Chem. Soc. 128 (44): 14254–14255. doi:10.1021/ja066405m. PMID   17076488.
  21. ↑ Nelson, David L.; Cox, Michael M. (2008). Principles of Biochemistry (5th ed.). W. H. Freeman. pp. 272–274. ISBN   978-1429208925.
  22. ↑ PATIL, SHARANABASAPPA B.; P., GOURAMMA; JALDE, SHIVAKUMAR S. (2021-07-15). "Medicinal Significance of Novel Coumarins: A Review". International Journal of Current Pharmaceutical Research: 1–5. doi:10.22159/ijcpr.2021v13i4.42733. ISSN   0975-7066. S2CID   238840705.
  23. ↑ Marlaire, Ruth (3 March 2015). "NASA Ames reproduces the building blocks of life in laboratory" (Press release). NASA . Retrieved 5 March 2015.
  24. ↑ Nuevo, M.; Chen, Y. J.; Hu, W. J.; Qiu, J. M.; Wu, S. R.; Fung, H. S.; Yih, T. S.; Ip, W. H.; Wu, C. Y. R. (2014). "Photo-irradiation of pyrimidine in pure H2O ice with high-energy ultraviolet photons" (PDF). Astrobiology. 14 (2): 119–131. Bibcode:2014AsBio..14..119N. doi:10.1089/ast.2013.1093. PMC   3929345 . PMID   24512484.
  25. ↑ Sandford, S. A.; Bera, P. P.; Lee, T. J.; Materese, C. K.; Nuevo, M. (6 February 2014). Photosynthesis and photo-stability of nucleic acids in prebiotic extraterrestrial environments (PDF). Topics of Current Chemistry. Topics in Current Chemistry. Vol. 356. pp. 123–164. Bibcode:2014ppna.book..123S. doi:10.1007/128_2013_499. ISBN   978-3-319-13271-6. PMC   5737941 . PMID   24500331., also published as Barbatti, M.; Borin, A. C.; Ullrich, S. (eds.). "14: Photosynthesis and photo-stability of nucleic acids in prebiotic extraterrestrial environments". Photoinduced phenomena in nucleic acids. Berlin, Heidelberg: Springer-Verlag. p. 499.
  26. ↑ Becker S, Feldmann J, Wiedemann S, Okamura H, Schneider C, Iwan K, Crisp A, Rossa M, Amatov T, Carell T. Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides. Science. 2019 Oct 4;366(6461):76-82. doi: 10.1126/science.aax2747. PMID 31604305
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.