Facile Stereospecific Synthesis of a-Anomeric 2'-Deoxynucleosides

Shinozuka, Kazuo; Hirota, Yoshiki; Morita, Tsutomu; Sawai, Hiroaki

doi:10.3987/com-92-6125

Cited by 7 publications

(2 citation statements)

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“…In light of the significant anti-HIV activity of the purine nucleoside β- d -2‘,3‘-dideoxyadenosine ( d -ddA) and its recognized susceptibility to degradation by the action of adenosine deaminase 5 and purine nucleoside phosphorylase, the realization of possible resistance of inactive metabolite formation in this manner was initially pursued. The strategy used for the synthesis of spirocyclic congeners 11 and 24 involved S N 2-type displacement of halide ion from chlorides such as 6 with the sodium salt of 6-chloropurine. − This reactive 1-chloro spirofuranose was prepared nonstereoselectively by Dibal-H reduction of the enantiopure lactone 4 followed by exposure to triphenylphosphine and carbon tetrachloride in THF at 50 °C . The generation of an epimeric mixture was not a major concern in that Hildebrand and Wright have demonstrated that epimerization occurs readily in such systems …”

Section: Resultsmentioning

confidence: 99%

Conformationally Constrained Purine Mimics. Incorporation of Adenine and Guanine into Spirocyclic Nucleosides

2004

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Directed syntheses of spirocyclic nucleosides featuring adenine and guanine as the nucleobases have been successfully developed. The key starting materials are the enantiomerically pure spiro lactones 4, 15, and 28, which have proven amenable to conversion to anomeric mixtures of chloro sugars. The latter can enter into glycosidation by SN2 displacement with the sodium salts of 6-chloropurine or 2-amino-6-chloropurine. In the saturated series, the chromatographic separation of 18 from 19 was possible. Where 33 and 34 are concerned, their relatively rapid rate of epimerization precluded this. Mimics 35-37 resisted isolation as pure anomers. The configurational assignments are based on the thermal interconversions and supporting MM3 steric energy calculations. Added corroboration was gained from a crystallographic analysis of 8. Although removal of the TBS protecting groups in all late-stage guanine intermediates proved to be problematical, the pair of hydroxyl groups in 37 could be introduced by proper recourse to the oxidation of 36 with ruthenium tetraoxide.

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Section: Resultsmentioning

confidence: 99%

Conformationally Constrained Purine Mimics. Incorporation of Adenine and Guanine into Spirocyclic Nucleosides

2004

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“…To obtain more knowledge of crystal structures of �-d-2 0deoxyribonucleosides with a canonical nucleobase, we performed a single-crystal X-ray analysis of �-d-2 0 -deoxyadenosine (1). �-d-2 0 -Deoxyadenosine (1) had been synthesized previously by Ness andFletcher in 1960 (Ness &Fletcher, 1960), and improved synthetic methods were reported by Robins (Robins & Robins, 1965) and Shinozuka (Shinozuka et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

α-D-2′-Deoxyadenosine, an irradiation product of canonical DNA and a component of anomeric nucleic acids: crystal structure, packing and Hirshfeld surface analysis

Leonard,

Zhang,

Budow-Busse

et al. 2024

Acta Crystallogr C

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α-D-2′-Deoxyribonucleosides are products of the γ-irradiation of DNA under oxygen-free conditions and are constituents of anomeric DNA. They are not found as natural building blocks of canonical DNA. Reports on their conformational properties are limited. Herein, the single-crystal X-ray structure of α-D-2′-deoxyadenosine (α-dA), C10H13N5O3, and its conformational parameters were determined. In the crystalline state, α-dA forms two conformers in the asymmetric unit which are connected by hydrogen bonds. The sugar moiety of each conformer is arranged in a `clamp'-like fashion with respect to the other conformer, forming hydrogen bonds to its nucleobase and sugar residue. For both conformers, a syn conformation of the nucleobase with respect to the sugar moiety was found. This is contrary to the anti conformation usually preferred by α-nucleosides. The sugar conformation of both conformers is C2′-endo, and the 5′-hydroxyl groups are in a +sc orientation, probably due to the hydrogen bonds formed by the conformers. The formation of the supramolecular assembly of α-dA is controlled by hydrogen bonding and stacking interactions, which was verified by a Hirshfeld and curvedness surface analysis. Chains of hydrogen-bonded nucleobases extend parallel to the b direction and are linked to equivalent chains by hydrogen bonds involving the sugar moieties to form a sheet. A comparison of the solid-state structures of the anomeric 2′-deoxyadenosines revealed significant differences of their conformational parameters.

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Synthesis Of Nucleosides

Vorbrüggen¹,

1999

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This chapter deals with the synthesis of nucleosides (e.g., the formation of N ‐glycosides of sugars such as D ‐ribose or 2‐deoxy‐D‐ribose with heterocyclic nitrogen bases). The methods of nucleoside synthesis have been treated in a number of reviews and monographs. It is now generally accepted that nucleosides were among the first organic compounds formed at the start of evolution in the early history of our planet earth. To support this point, guanine and adenine were heated with D ‐ribose in seawater, which contains the Lewis acid magnesium chloride as catalyst. One thus obtained the nucleosides guanosine and adenosine together with comparable yields of unnatural α‐nucleosides. The latter were gradually photoanomerized to the thermodynamically more stable compounds in overall yields of 5–6%. The furanose form of ribose reacts faster than the pyranose form. Corresponding syntheses of the pyrimidine nucleosides uridine and cytidine from uracil , cytosine and ribose are more problematic and remain an enigma. The recent conversion of glycolaldehyde‐ O ‐phosphate and formaldehyde to ribose‐2,4‐di‐ O ‐phosphate might give new insights into the prebiotic syntheses of uridine and cytidine. The evidence and hypotheses for these prebiotic conversions and the evolution of RNA, as well as the implications of an “RNA World,” have been reviewed. These RNA nucleosides are reduced in vivo as 5′‐ O ‐diphosphates by ribonucleotide reductases to the corresponding 2′‐deoxynucleosides—the building blocks of DNA such as 2′‐deoxyguanosine. The thermodynamically controlled synthesis of these four building blocks of RNA has implications for the design of efficient, high yielding, new methods for the synthesis of the naturally occurring nucleosides, nucleoside antibiotics, and modified nucleosides that may serve as antimetabolites to fight viral and parasitic diseases and cancer. The nucleoside rings in this chapter are depicted arbitrarily in the anti conformation, as occurs predominantly in the crystal and solution (based primarily on NOE‐ 1 H‐ and 13 C‐NMR measurements) forms of pyrimidine nucleosides. Only a few nucleosides, such as 6‐methyluridine, occur with the heterocyclic ring predominantly in the syn conformation. The synthesis of C ‐nucleosides has been reviewed previously and is not covered in this review.

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Facile Stereospecific Synthesis of a-Anomeric 2'-Deoxynucleosides

Cited by 7 publications

References 0 publications

Conformationally Constrained Purine Mimics. Incorporation of Adenine and Guanine into Spirocyclic Nucleosides

Conformationally Constrained Purine Mimics. Incorporation of Adenine and Guanine into Spirocyclic Nucleosides

α-D-2′-Deoxyadenosine, an irradiation product of canonical DNA and a component of anomeric nucleic acids: crystal structure, packing and Hirshfeld surface analysis

Synthesis Of Nucleosides

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