Convenient Synthesis of Fluorinated Nucleosides With Perfluoroalkanesulfonyl Fluorides

Takamatsu, Satoshi; Katayama, Satoshi; Hirose, Naoko; Cock, E. De; Schelkens, Geert; Demillequand, Marc; Brepoels, Jozef; Izawa, Kunisuke

doi:10.1081/ncn-120016572

Cited by 27 publications

(21 citation statements)

References 44 publications

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“…This simple and highly efficient method was successfully used for the preparation of fluorinated nucleosides 11,12. The synthesis of lodenosine demonstrates the applicability on the industrial scale 12c. A closely related method for the fluorination of primary, secondary and even tertiary alcohols was disclosed by Yin and co‐workers 13.…”

Section: Alkyl Nonaflatesmentioning

confidence: 89%

Nine Times Fluoride can be Good for your Syntheses. Not just Cheaper: Nonafluorobutanesulfonates as Intermediates for Transition Metal‐Catalyzed Reactions

2009

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How much fluoride is good for a strong electron-withdrawing effect? In this review we summarize recent results on the use of perfluoroalkanesulfonates, in particular of the cost effective nonafluorobutanesulfonates (nonaflates), in transition metal-catalyzed reactions and a few other typical transformations. During the last decade many advantages over the commonly used triflates have been discovered. The generation of alkenyl and (het)aryl nonaflates and their applications in metal-catalyzed processes such as Heck, Suzuki, Sonogashira, Stille, and Negishi couplings or amination reactions are described. Although far from a systematic investigation, all the presented results clearly demonstrate the many advantages of nonaflates and of similar higher fluorinated sulfonates in laboratory and industrial scale organic synthesis.

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Section: Alkyl Nonaflatesmentioning

confidence: 89%

Nine Times Fluoride can be Good for your Syntheses. Not just Cheaper: Nonafluorobutanesulfonates as Intermediates for Transition Metal‐Catalyzed Reactions

2009

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“…Use of nonafluorobutanesulfonyl fluoride 12 provided the nonaflate intermediate 14 which was recalcitrant to further displacement with fluoride. Triflation of the secondary alcohol in 13 followed by reaction with cesium fluoride in tert -butanol 13 at elevated temperatures did not yield the desired fluorinated nucleoside and only decomposition prevailed.…”

mentioning

confidence: 99%

Synthesis, Duplex Stabilization and Structural Properties of a Fluorinated Carbocyclic LNA Analogue

et al. 2012

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DNA oligonucleotides modified with nucleoside monomers which have an electron withdrawing group (EWG) at the 2′‐position of the furanose ring form more stable duplexes with complementary RNA as compared to unmodified DNA. Here we show that an anti‐periplanar orientation of the nucleobase and the 2′‐EWG is important for optimal duplex stabilization even for nucleic acid analogues with conformationally locked furanose rings.

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“…Gratifyingly, fluorination of the secondary equatorial 4′-hydroxyl group to the axial fluoride 26 proceeded smoothly using DBU and nonafluorobutanesulfonyl fluoride as the fluorinating agent. (41) Attempts to eliminate the 6′-iodide in 26 using DBU as reported previously resulted in variable results. The major byproduct of this reaction, as indicated by LC–MS analysis of the crude reaction mixtures, appeared to be adducts arising from nucleophilic displacement of the iodide with DBU.…”

Section: Resultsmentioning

confidence: 94%

Synthesis and Antisense Properties of Fluoro Cyclohexenyl Nucleic Acid (F-CeNA), a Nuclease Stable Mimic of 2′-Fluoro RNA

Seth

Jazayeri

et al. 2012

J. Org. Chem.

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We report the design and synthesis of 2′-fluoro cyclohexenyl nucleic acid (F-CeNA) pyrimidine phosphoramidites and the synthesis and biophysical, structural, and biological evaluation of modified oligonucleotides. The synthesis of the nucleoside phosphoramidites was accomplished in multigram quantities starting from commercially available methyl-D-mannose pyranoside. Installation of the fluorine atom was accomplished using nonafluorobutanesulfonyl fluoride, and the cyclohexenyl ring system was assembled by means of a palladium-catalyzed Ferrier rearrangement. Installation of the nucleobase was carried out under Mitsunobu conditions followed by standard protecting group manipulations to provide the desired pyrimidine phosphoramidites. Biophysical evaluation indicated that F-CeNA shows behavior similar to that of a 2′-modified nucleotide, and duplexes with RNA showed slightly lower duplex thermostability as compared to that of the more rigid 3′-fluoro hexitol nucleic acid (FHNA). However, F-CeNA modified oligonucleotides were significantly more stable against digestion by snake venom phosphodiesterases (SVPD) as compared to unmodified DNA, 2′-fluoro RNA (FRNA), 2′-methoxyethyl RNA (MOE), and FHNA modified oligonucleotides. Examination of crystal structures of a modified DNA heptamer duplex d(GCG)-T*-d(GCG):d(CGCACGC) by X-ray crystallography indicated that the cyclohexenyl ring system exhibits both the 3H2 and 2H3 conformations, similar to the C3′-endo/C2′-endo conformation equilibrium seen in natural furanose nucleosides. In the 2H3 conformation, the equatorial fluorine engages in a relatively close contact with C8 (2.94 Å) of the 3′-adjacent dG nucleotide that may represent a pseudo hydrogen bond. In contrast, the cyclohexenyl ring of F-CeNA was found to exist exclusively in the 3H2 (C3′-endo like) conformation in the crystal structure of the modified A-form DNA decamer duplex [d(GCGTA)-T*-d(ACGC)]2. In an animal experiment, a 16-mer F-CeNA gapmer ASO showed similar RNA affinity but significantly improved activity compared to that of a sequence matched MOE ASO, thus establishing F-CeNA as a useful modification for antisense applications.

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Convenient Synthesis of Fluorinated Nucleosides With Perfluoroalkanesulfonyl Fluorides

Abstract: Perfluoroalkanesulfonyl fluorides are effective dehydroxy-fluorination agents for the hydroxyl group at the sugar moiety of nucleoside derivatives and give the corresponding fluorinated nucleosides in good yield with an inversion of configuration in a single step.

Cited by 27 publications

References 44 publications

Nine Times Fluoride can be Good for your Syntheses. Not just Cheaper: Nonafluorobutanesulfonates as Intermediates for Transition Metal‐Catalyzed Reactions

Nine Times Fluoride can be Good for your Syntheses. Not just Cheaper: Nonafluorobutanesulfonates as Intermediates for Transition Metal‐Catalyzed Reactions

Synthesis, Duplex Stabilization and Structural Properties of a Fluorinated Carbocyclic LNA Analogue

Synthesis and Antisense Properties of Fluoro Cyclohexenyl Nucleic Acid (F-CeNA), a Nuclease Stable Mimic of 2′-Fluoro RNA

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