1988
DOI: 10.1021/jm00403a026
|View full text |Cite
|
Sign up to set email alerts
|

Nucleosides. 150. Synthesis and some biological properties of 5-monofluoromethyl, 5-difluoromethyl, and 5-trifluoromethyl derivatives of 2'-deoxyuridine and 2'-deoxy-2'-fluoro-.beta.-D-arabinofuranosyluracil

Abstract: A new synthesis of 5-(monofluoromethyl)- and 5-(difluoromethyl)-2'-deoxy-2'-fluoro-beta-D-arabinofuranosyluracil (F-FMAU and F2-FMAU) is reported. 3',5'-Di-O-(tert-butyldiphenyl)silylated thymidine or FMAU was photochemically brominated with NBS to the corresponding alpha-monobromide, which was hydrolyzed to the 5-hydroxymethyl derivative. Further oxidation of the latter with MnO2 afforded the 5-formyluracil nucleoside. Treatment of these nucleosides with DAST in CH2Cl2 gave the protected alpha-fluorinated nuc… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

1
10
0

Year Published

1988
1988
2022
2022

Publication Types

Select...
7
1

Relationship

0
8

Authors

Journals

citations
Cited by 15 publications
(11 citation statements)
references
References 1 publication
1
10
0
Order By: Relevance
“…Synthesis of 2‘- C -β-Difluoromethylribonucleosides. Diethylaminosulfur trifluoride (DAST) under mild conditions converts aldehydes, including those appended to nucleosides, to a difluoromethyl group. ,, On this basis we prepared 2‘- C -β-formyluridine as a putative precursor to 2‘- C -difluoromethyluridine via DAST-mediated fluorination. We obtained 1,3,5-tri- O -benzoyl-2-oxo-α- d - erythro -pentofuranose 2 as previously described by oxidation of 1,3,5-tri- O -benzoyl-α- d -ribofuranose 1 with Dess−Martin periodinane.…”
Section: Resultsmentioning
confidence: 99%
“…Synthesis of 2‘- C -β-Difluoromethylribonucleosides. Diethylaminosulfur trifluoride (DAST) under mild conditions converts aldehydes, including those appended to nucleosides, to a difluoromethyl group. ,, On this basis we prepared 2‘- C -β-formyluridine as a putative precursor to 2‘- C -difluoromethyluridine via DAST-mediated fluorination. We obtained 1,3,5-tri- O -benzoyl-2-oxo-α- d - erythro -pentofuranose 2 as previously described by oxidation of 1,3,5-tri- O -benzoyl-α- d -ribofuranose 1 with Dess−Martin periodinane.…”
Section: Resultsmentioning
confidence: 99%
“…Watanabe later used similar conditions with arabinofuranosyluracil iodide to yield the desired product in 61% yield. 111 Instead of using CF 3 I, Yamashita and co-workers used CF 3 Br in the presence of Cu powder and catalytic DMAP in pyridine/DMF for the trifluoromethylation of 5-iododeoxyuridine (Scheme 48). 112 Interestingly, the desired product was obtained in comparable yield to that observed for the trifluoromethylation of similar 5-iododeoxyuridines.…”
Section: Trifluoromethylation Of Halo-nucleosidesmentioning
confidence: 99%
“…Alauddin and co workers and more recently Shields and co workers have developed a general procedure for the synthesis of 18 F labeled, 5-substituted-2‘-deoxy-2‘-[ 18 F]fluoroarabinofuranosyluracil derivatives, such as [ 18 F]FMAU, [ 18 F]FBAU, [ 18 F]FAU, etc., and are currently evaluating their potential as PET markers for cellular proliferation. The 5-substituted thymidine derivatives have also been shown to be good substrates for HSV1-TK. , Our aim was to synthesize 5-substituted derivatives of 2‘-fluoro-2‘-deoxythymidine, with a range of different hydrophobicities, and then to evaluate them as potential radiolabeled PET reporter probes for imaging HSV1-tk gene expression. Hydrophobic derivatives are of interest because the currently available probes are hydrophilic and do not readily cross the intact blood−brain barrier.…”
Section: Introductionmentioning
confidence: 99%
“…A variety of 5-substituted thymidine derivatives were previously synthesized and evaluated for their potential as antiherpes agents. The primary mechanism of action was based on the ability of herpes viral thymidine kinase to phosphorylate the thymidine derivatives, which in turn would be incorporated into viral DNA causing multistrand breaks leading to destruction of virus. We hypothesized that antiviral efficacy of a particular molecule is a good indicator of its rate of phosphorylation.…”
Section: Introductionmentioning
confidence: 99%