Synthesis of pyrimidine 3'-allyl-2',3'-dideoxyribonucleosides by free-radical coupling

Chu, Chung K.; Doboszewski, Bogdan; Schmidt, Walter F.; Ullas, G. V.; Roey, P. Van

doi:10.1021/jo00272a062

Cited by 55 publications

(21 citation statements)

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“…The 5′-terminal fragments ( 8 , 10 , 12 ) were obtained using standard DNA synthesis done in the unconventional 5′→3′ direction ( 13 ) on an Expedite 8900 DNA synthesizer. Figure 2 shows the scheme for their preparation.…”

Section: Methodsmentioning

confidence: 99%

Dynamic assembly of primers on nucleic acid templates

Leal

Sukeda

Benner

2006

Nucleic Acids Research

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A strategy is presented that uses dynamic equlibria to assemble in situ composite DNA polymerase primers, having lengths of 14 or 16 nt, from DNA fragments that are 6 or 8 nt in length. In this implementation, the fragments are transiently joined under conditions of dynamic equilibrium by an imine linker, which has a dissociation constant of ∼1 μM. If a polymerase is able to extend the composite, but not the fragments, it is possible to prime the synthesis of a target DNA molecule under conditions where two useful specificities are combined: (i) single nucleotide discrimination that is characteristic of short oligonucleotide duplexes (four to six nucleobase pairs in length), which effectively excludes single mismatches, and (ii) an overall specificity of priming that is characteristic of long (14 to 16mers) oligonucleotides, potentially unique within a genome. We report here the screening of a series of polymerases that combine an ability not to accept short primer fragments with an ability to accept the long composite primer held together by an unnatural imine linkage. Several polymerases were found that achieve this combination, permitting the implementation of the dynamic combinatorial chemical strategy.

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Section: Methodsmentioning

confidence: 99%

Dynamic assembly of primers on nucleic acid templates

Leal

Sukeda

Benner

2006

Nucleic Acids Research

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“…T w o basic approaches exist for the synthesis of these molecules: the direct two-carbon homologation of nucleosides, or the preparation of the branched-chain sugar followed by the attachment of the nitrogenous base. The recent report (17) that the tributyltin-mediated radical allylation using 3'-thiocarbonate derivatives of thymidine occurs with high stereoselectivity provided us with a rapid entry to the branched-chain system. The oxidative cleavage of the olefinic bond of the 3'-C-ally1 nucleoside 1 to the aldehyde Can A B has also been reported (18) but no experimental details were given.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of the thymidine building blocks for a nonhydrolyzable DNA analogue

Kawai¹,

Wang²,

Just³

1992

Can. J. Chem.

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The 3′-deoxy-3′-C-(2″-hydroxyethyl)thymidine derivatives 4 and 13 were efficiently synthesized from either thymidine via a known 3′-radical allylation, or from the branched-chain furanose 5 involving the removal of the 2′-hydroxyl after stereospecific nucleosidation. The 5′-deoxy-5′-thiothymidine 20 was prepared via a regiospecific Mitsunobu coupling, providing the third unit required for the synthesis of sulfide-linked DNA analogues.

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“…Crystal Structure Determination. The crystal structures of six of the compounds were reported previously (15)(16)(17)(18). The structures of ddT and ddU are reported here.…”

Section: Methodsmentioning

confidence: 93%

Correlation between preferred sugar ring conformation and activity of nucleoside analogues against human immunodeficiency virus.

Roey

Salerno

Chu

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Analysis of the solid-state conformations of six active and two inactive anti-human immunodeficiency virus nucleoside analogues is used to correlate conformational features with the relative activities of the compounds. Ten of the 11 observations of the active compounds (3'-azido-3'-deoxythymidine, 3'-azido-2',3'-dideoxyuridine, 3'-azido-2',3'-dideoxy-5-ethyluridine, 2',3'-dideoxyadenosine, 2',3'-dideoxycytidine, and 3'-deoxythymidine) have C3'-exo sugar ring conformations. The only exception is one of the two molecules of 3'-deoxythymidine. Four have unusual low anti glycosyl link conformations coupled with unusual C3'-exo/C4'-endo sugar ring conformations. The inactive compounds, 2',3'-dideoxyuridine and 3'-(propyl-2-ene)-2',3'-dideoxyuridine, have C3'-endo conformations. The C3'-exo and C3'-endo conformations place C5' in axial and equatorial positions, respectively. This affects the location of the 5'-hydroxyl group in relation to the location of the base. The 5'-hydroxyl group is the site of phosphorylation of the nucleoside and the observation of this conformational preference of the active compounds may be of importance for the development of new nucleosides with activity against human immunodeficiency virus.

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Synthesis of pyrimidine 3'-allyl-2',3'-dideoxyribonucleosides by free-radical coupling

Cited by 55 publications

References 0 publications

Dynamic assembly of primers on nucleic acid templates

Dynamic assembly of primers on nucleic acid templates

Synthesis of the thymidine building blocks for a nonhydrolyzable DNA analogue

Correlation between preferred sugar ring conformation and activity of nucleoside analogues against human immunodeficiency virus.

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