Unexpected formation of 2′-deoxy-N3-(3,3,3-trifluoro-1-propenyl)uridine via a Michael-type addition to 3,3,3-trifluoropropyne

Chirakul, Panadda; Sigurdsson, Snorri Th.

doi:10.1016/s0040-4039(03)01702-7

Cited by 9 publications

(9 citation statements)

References 13 publications

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“… Stille coupling reactions were carried out on 5′-benzoyl-5-iodo-2′-deoxyuridine ( 18 ) or NMe- 18 . The latter was prepared by benzoylating 5-iodo-3-methyl-2′-doxyuridine . The vinyl substituted nucleosides were converted to the aldehyde products using a one-pot osmylation, periodate oxidation procedure .…”

Section: Resultssupporting

confidence: 85%

“…The latter was prepared by benzoylating 5-iodo-3-methyl-2′-doxyuridine. 30 The vinyl substituted nucleosides were converted to the aldehyde products using a one-pot osmylation, periodate oxidation procedure. 31 During the course of the UPLC product analyses discussed below, we determined that 16 was inseparable from the internal standard (5′-benzoyl-2′-deoxyuridine, BzU ).…”

Section: Resultsmentioning

confidence: 99%

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Independent Generation and Reactivity of Thymidine Radical Cations

2017

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Thymidine radical cation (1) is produced by ionizing radiation and has been invoked as an intermediate in electron transfer in DNA. Previous studies on its structure and reactivity have utilized thymidine as a precursor, which limits quantitative product analysis because thymidine is readily reformed from 1. In this investigation, radical cation 1 is independently generated via β-heterolysis of a pyrimidine radical generated photochemically from an aryl sulfide. Thymidine is the major product (33%) from 1 at pH 7.2. Diastereomeric mixtures of thymidine glycol and the corresponding 5-hydroxperoxides resulting from water trapping of 1 are formed. Significantly lower yields of products such as 5-formyl-2′-deoxyuridine that are ascribable to deprotonation from the C5-methyl group of 1 are observed. Independent generation of the N3-methyl analogue of 1 (NMe-1) produces considerably higher yields of products derived from water trapping, and these products are formed in much higher yields than those attributable to the C5-methyl group deprotonation in NMe-1. N3-Methyl-thymidine is, however, the major product and is produced in as high as 70% yield when the radical cation is produced in the presence of excess thiol. The effects of exogenous reagents on product distributions are consistent with the formation of diffusively free radical cations (1, NMe-1). This method should be compatible with producing radical cations at defined positions within DNA.

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Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Independent Generation and Reactivity of Thymidine Radical Cations

2017

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“…[15] On treatment of 2Ј-deoxy-5-iodouridine with 3,3,3-trifluoropropyne in the presence of a palladium catalyst, Sigurdsson obtained 2Ј-deoxy-N 3 -(3,3,3-trifluoropropenyl)-uridine instead of the expected coupling product. [16] We have not found any literature report involving the production of a purine or pyrimidine α-fluoroenamine or a stable (not undergoing hydrolysis) α-fluoroenamine. The only reported α-haloenamines of nucleic acid bases were the mono-, di-and trichloroenamines of purine and pyrimidine bases obtained by Zemlicka.…”

Section: Introductionmentioning

confidence: 87%

A Convenient Method for the Synthesis of Stable α‐Fluoro Enamines of Nucleobases

2007

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Treatment of a whole set of nucleic acid bases and related derivatives 4, 9 and 10 with electron‐deficient hexafluoropropene or 1,1,3,3,3‐pentafluoropropene in the presence of sodium hydride gave the corresponding N1 and N9 stable fluorinated enamines with high regioselectivity. This alkylation is a result of a Michael type addition–elimination process and gave the desired products 2a–10a and 2b–10b as E/Z mixtures. Unexpectedly, treatment of 2b with tert‐butyllithium and subsequently with [D4]methanol gave different results for E and Z stereoisomers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

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“…The N ‐trifluoropropenylation of enamides such as pyrrolidin‐2‐one can be achieved through the palladium‐ [11a] or copper‐catalyzed [11b] trifluoromethylation of N ‐vinylpyrrolidin‐2‐one with CF 3 I or under photocatalytic conditions (Figure 1a), [11c–e] while the same product can be obtained with trifluoropropionaldehyde (Figure 1b) [11f] . The use of 3,3,3‐trifluoropropyne gas as a C 2 ‐CF 3 surrogate requires the handling of gaseous reagent, but it was successfully applied as Michael acceptor in its reaction with 2’‐deoxyiodouridine used for iodinated DNA bases (Figure 1c) [11g] . The NH functionalities in uracil and thymine can be trifluoropropenylated with 2‐bromo‐3,3,3‐trifluoropropene with moderate stereoselectivity (Figure 1c) [11h] …”

Section: Figurementioning

confidence: 99%

Stereoselective Direct N‐Trifluoropropenylation of Heterocycles with a Hypervalent Iodonium Reagent

Csenki

Mészáros

Gonda

et al. 2021

Chemistry A European J

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The availability and synthesis of fluorinated enamine derivatives such as N‐(3,3,3‐trifluoropropenyl)heterocycles are challenging, especially through direct functionalization of the heterocyclic scaffold. Herein, a stereoselective N‐trifluoropropenylation method based on the use of a bench‐stable trifluoropropenyl iodonium salt is described. This reagent enables the straightforward trifluoropropenylation of various N‐heterocycles under mild reaction conditions, providing trifluoromethyl enamine type moieties with high stereoselectivity and efficiency.

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Unexpected formation of 2′-deoxy-N3-(3,3,3-trifluoro-1-propenyl)uridine via a Michael-type addition to 3,3,3-trifluoropropyne

Cited by 9 publications

References 13 publications

Independent Generation and Reactivity of Thymidine Radical Cations

Independent Generation and Reactivity of Thymidine Radical Cations

A Convenient Method for the Synthesis of Stable α‐Fluoro Enamines of Nucleobases

Stereoselective Direct N‐Trifluoropropenylation of Heterocycles with a Hypervalent Iodonium Reagent

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