2009
DOI: 10.1021/jm900852b
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Discovery of a New Template for Anticancer Agents: 2′-deoxy-2′-fluoro-4′-selenoarabinofuranosyl-cytosine (2′-F-4′-Seleno-ara-C)

Abstract: The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was mo… Show more

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Cited by 46 publications
(29 citation statements)
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“…2′‐F‐4′‐Thio‐ara‐C having successfully been developed as an anticancer agent,12 it was of interest to synthesize the corresponding 4′‐selenonucleosides in the hope of developing a potential therapeutic nucleoside. To achieve this goal, Jeong and co‐workers successfully synthesized the selenoarabinofuranosyl‐cytosine, 2′‐F‐4′‐seleno‐ara‐C ( 51 ) from 4′‐selenouridine ( 7 ), using selenium‐assisted DAST fluorination (short term used in the sequel: fluorination) as the key step, as shown in Scheme 13…”
Section: Development Of 4′‐selenonucleosidesmentioning
confidence: 99%
See 1 more Smart Citation
“…2′‐F‐4′‐Thio‐ara‐C having successfully been developed as an anticancer agent,12 it was of interest to synthesize the corresponding 4′‐selenonucleosides in the hope of developing a potential therapeutic nucleoside. To achieve this goal, Jeong and co‐workers successfully synthesized the selenoarabinofuranosyl‐cytosine, 2′‐F‐4′‐seleno‐ara‐C ( 51 ) from 4′‐selenouridine ( 7 ), using selenium‐assisted DAST fluorination (short term used in the sequel: fluorination) as the key step, as shown in Scheme 13…”
Section: Development Of 4′‐selenonucleosidesmentioning
confidence: 99%
“…Motivated by the potent anticancer activity of 2′‐F‐4′‐seleno‐ara‐C13 ( 51 ), with the 2′‐ arabino configuration, Jeong and co‐workers further investigated the structure–activity relationships of 2′‐modified 2′‐deoxy‐4′‐selenoarabinofuranosyl pyrimidines with azido, fluoro, and hydroxy substituents (Scheme ) 17. The synthesis of the 2′‐azido‐4′‐selenonucleosides 82 proceeded from selenoxide 4 , which was condensed with various silylated pyrimidine bases such as uracil, thymine, and 5‐halouracils by Pummerer‐type condensation, followed by removal of protecting groups to yield 4′‐selenoribofuranosyl pyrimidines 79 .…”
Section: Development Of 4′‐selenonucleosidesmentioning
confidence: 99%
“…In this reaction, sulfur took an active part during fluorination and assisted to produce the desired 2′-arabino fluoro-compound. 32 The synthesis of a 4′-seleno-2′-fluoro-arabinofuranosyluracil has also been reported, 33 in which selenium played a role similar to that of the sulfur in 4′-thio-pyrimidine. Most recently, we reported a synthesis of 2′-arabino-fluoro-derivative ([ 18 F]FMAU) for the 4′-oxo-nucleoside by stereospecific fluorination.…”
Section: Introductionmentioning
confidence: 99%
“…[7] Oxygen, sulfur,a nd methylene have ac hemical isosteric or bioisosteric relationship with selenium.B ased on this concept, we have recently reported various 4'-selenonucleosides with diverseb iological activities. [8] Interestingly,2 '-F-4'-Se-AraC [9] exhibited potent anticancer activity,b ut it was not converted into the corresponding triphosphate, unlike AraC, inhibiting cellular DNA polymerase after being transformed into the triphosphate form. These resultsi ndicatedt hat it did not serve as the substrate for cellular nucleoside/nucleotide kinases, which was attributed to steric repulsion between bulky selenium atom and cellular kinases.T os tudy this hypothesis, we have synthesized 5'-homo-4'-selenonucleosides, in which steric repulsion might be neutralized by one-carbon homologation, and analyzed their intracellular metabolites.…”
Section: Introductionmentioning
confidence: 99%