- Selective Prebiotic Synthesis of α-Threofuranosyl Cytidine by Photochemical Anomerization
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The structure of life's first genetic polymer is a question of intense ongoing debate. The “RNA world theory” suggests RNA was life's first nucleic acid. However, ribonucleotides are complex chemical structures, and simpler nucleic acids, such as threose nucleic acid (TNA), can carry genetic information. In principle, nucleic acids like TNA could have played a vital role in the origins of life. The advent of any genetic polymer in life requires synthesis of its monomers. Here we demonstrate a high-yielding, stereo-, regio- and furanosyl-selective prebiotic synthesis of threo-cytidine 3, an essential component of TNA. Our synthesis uses key intermediates and reactions previously exploited in the prebiotic synthesis of the canonical pyrimidine ribonucleoside cytidine 1. Furthermore, we demonstrate that erythro-specific 2′,3′-cyclic phosphate synthesis provides a mechanism to photochemically select TNA cytidine. These results suggest that TNA may have coexisted with RNA during the emergence of life.
- Colville, Ben W. F.,Powner, Matthew W.
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supporting information
p. 10526 - 10530
(2021/03/30)
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- MAGNESIUM COMPOSITIONS AND USES THEREOF FOR NEUROLOGICAL DISORDERS
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A composition for administration to a subject, such as oral administration to a subject, for example, has been provided. Such a composition may comprise at least one magnesium-counter ion compound. A magnesium-counter ion composition described herein may be useful for any of a variety of applications provided herein, such as maintaining, enhancing, and/or improving health, nutrition, and/or another condition of a subject, and/or cognitive, learning, and/or memory function. A magnesium-counter ion composition provided herein may be useful for administration to a subject presenting magnesium deficiency, mild cognitive impairment, Alzheimer's disease, attention deficit hyperactivity disorder, ALS, Parkinson's disease, diabetes, migraine, anxiety disorder, mood disorder, and/or hypertension. A kit, method, and other associated technology are also provided.
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Paragraph 0194
(2017/05/07)
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- A Scalable Synthesis of α-L-Threose Nucleic Acid Monomers
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Recent advances in polymerase engineering have made it possible to copy information back and forth between DNA and artificial genetic polymers composed of TNA (α-l-threofuranosyl-(3′,2′) nucleic acid). This property, coupled with enhanced nuclease stability relative to natural DNA and RNA, warrants further investigation into the structural and functional properties of TNA as an artificial genetic polymer for synthetic biology. Here, we report a highly optimized chemical synthesis protocol for constructing multigram quantities of TNA nucleosides that can be readily converted to nucleoside 2′-phosphoramidites or 3′-triphosphates for solid-phase and polymerase-mediated synthesis, respectively. The synthetic protocol involves 10 chemical transformations with three crystallization steps and a single chromatographic purification, which results in an overall yield of 16-23% depending on the identity of the nucleoside (A, C, G, T).
- Sau, Sujay P.,Fahmi, Nour Eddine,Liao, Jen-Yu.,Bala, Saikat,Chaput, John C.
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p. 2302 - 2307
(2016/04/04)
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- NOVEL ANTIVIRAL COMPOUNDS, A PROCESS FOR THEIR PREPARATION, AND THEIR USE FOR TREATING VIRAL INFECTIONS
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The present invention relates to novel pro-drugs of L-2'-deoxythreose nucleoside phosphonates, such as phosphoramidate, phosphorodiamidate and phospho-diester prodrugs. The invention also relates to a process for preparing these novel prodrugs of nucleoside phosphonates. The invention also relates to the use of these novel phosphonatemodified nucleosides to treat or prevent viral infections and their use to manufacture a medicine to treat or prevent viral infections, particularly infections with viruses belonging to the HBV family.
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Page/Page column 20; 21
(2017/01/05)
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- Nonenzymatic oligomerization of RNA by TNA templates
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(Diagram presented) Cytosine TNA promotes nonenzymatic, template-directed oligomerization of complementary activated rGMP, leading to selective and efficient formation of RNA products. This process models "genetic takeover" of a pre-RNA by RNA.
- Heuberger, Benjamin O.,Switzer, Christopher
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p. 5809 - 5811
(2007/10/03)
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- Method for synthesizing oxazinones
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New methods and intermediates are discussed for the stereospecific synthesis of oxazinone compounds.
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- Cyclic hydroxamates, especially multiply substituted [1,2]oxazinan-3-ones
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Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride - alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one.
- Wolfe, Saul,Wilson, Marie-Claire,Cheng, Ming-Huei,Shustov, Gennady V.,Akuche, Christiana I.
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p. 937 - 960
(2007/10/03)
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- The α-L-Threofuranosyl-(3′ → 2′)-oligonucleotide system ('TNA'): Synthesis and pairing properties
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Our studies of α-L-Threofuranosyl-(3′ → 2′)-oligonucleotides ('TNA') are part of a systematic experimental inquiry into the base-pairing properties of potentially natural nucleic acid alternatives taken from RNA's close structural neighborhood. TNA is an efficient Watson-Crick base-pairing system and has the capability of informational cross-pairing with both RNA and DNA. This property, together with the system's constitutional and (presumed) generational simplicity, warrants special scrutiny of TNA in the context of the search for chemical clues to RNA's origin.
- Schoening, Kai-Uwe,Scholz, Peter,Wu, Xiaolin,Guntha, Sreenivasulu,Delgado, Guillermo,Krishnamurthy, Ramanarayanan,Eschenmoser, Albert
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p. 4111 - 4153
(2007/10/03)
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