Synthesis and Biological Activity of a Series of Methylene-Expanded Oxetanocin Nucleoside Analogues

Jung, Michael E.; Toyota, Azumao; Clercq, Erik De; Balzarini, Jan

doi:10.1007/s007060200024

Cited by 8 publications

(18 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The α- and β-anomers of 12 were obtained in a 1:1 ratio. 7 Introduction of the one-carbon fragment at C 1 was accomplished by a C -glycosylation reaction using (CH 3 ) 3 SiCN (TMSCN) as the nucleophile. 11 Due to the neighboring effect of the C 2 acetate in 12 , only the β-anomer 13 was obtained in 93 % yield.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of Conformationally North-Locked Pyrimidine Nucleosides Built on an Oxabicyclo[3.1.0]hexane Scaffold

Ludek

Márquez

2011

J. Org. Chem.

View full text Add to dashboard Cite

Beginning with a known 3-oxabicyclo[3.1.0]hexane scaffold (I), the relocation of the fused cyclopropane ring bond and the shifting of the oxygen atom to an alternative location engendered a new 2-oxabicyclo[3.1.0]hexane template (II) that mimics more closely the tetrahydrofuran ring of conventional nucleosides. The synthesis of this new class of locked nucleosides involved a novel approach that required the isocyanate II (B = NCO) with a hydroxyl-protected scaffold as a pivotal intermediate that was obtained in eleven steps from a known dihydrofuran precursor. The completion of the nucleobases was successfully achieved by quenching the isocyanate with the lithium salts of the corresponding acrylic amides that led to the uracil and thymidine precursors in a single step. Ring closure of these intermediates led to the target, locked nucleosides. The anti-HIV activity of 29 (uridine analogue), 31 (thymidine analogue), and 34 (cytidine analogue) was explored in human osteosarcoma (HOS) cells or modified HOS cells (HOS-313) expressing the herpes simplex virus 1 thymidine kinase (HSV-1 TK). Only the cytidine analogue showed moderate activity in HOS-313 cells, which means that the compounds are not good substrates for the cellular kinases.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The diacetate 12 7 (1.10 g, 2.41 mmol) was dissolved in dry MeCN (20 mL) and TMSCN (1.08 g, 10.8 mmol) was added under argon at 0 °C. After adding a catalytic amount of BF 3 •Et 2 O (60 μL, 0.48 mmol) the mixture was allowed to reach room temperature and was stirred for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Conformationally North-Locked Pyrimidine Nucleosides Built on an Oxabicyclo[3.1.0]hexane Scaffold

Ludek

Márquez

2011

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Synthesis of 2,3-dihydrofuran derivatives from 2-chlorovinyl sulfones was described in some articles [18,24,30,43,44]. Thus, interaction of epoxy alcohol 47 with chlorovinyl sulfone 5 afforded intermediate ether 48.…”

Section: Synthesis Of Heterocycles From 2-chlorovinylsulfonesmentioning

confidence: 99%

Synthesis and Reactions of 2-Chlorovinyl Sulfones

Višņevska¹,

Абеле²

2011

Latvian Journal of Chemistry

View full text Add to dashboard Cite

Synthesis and Reactions of 2-Chlorovinyl Sulfones Methods for the preparation of unsubstituted (E)-2-chlorovinyl sulfo-nes are reviewed. Literature data on substitution of chlorine atom in 2-chlorovinyl sulfones leading to formation of different types of disub-stituted ethenes are presented also. Synthesis of novel heterocyclic compounds directly from 2-chlorovinyl sulfones is also included in the present review.

show abstract

“…We envisioned a synthetic approach that would also give access to the known apionucleosides 3 [6,7], their 3'-deoxy counterparts 2 [8,9,10,11], and inadvertently also the D-apio-L-furanose epimers 4-6. Furthermore, we planned to expand the potential of the 2',3'dideoxyapio nucleosides 1 and 4 as antiviral agents by synthesizing their phosphoramidate prodrugs 9, 10 and 11.…”

Section: Introductionmentioning

confidence: 99%

“…Since these phosphonates act as bioisosteres of the phosphorylated species 8 , we decided to reinvestigate the biological activity of these ddANs. We envisioned a synthetic approach that would also give access to the known apionucleosides 3 , , their 3′-deoxy counterparts 2 , − and inadvertently also the d -apio- l -furanose epimers 4 – 6 . Furthermore, we planned to expand the potential of the 2′,3′-dideoxyapio nucleosides 1 and 4 as antiviral agents by synthesizing their phosphoramidate prodrugs 9 , 10 and 11 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of an Apionucleoside Family and Discovery of a Prodrug with Anti-HIV Activity

et al. 2014

Self Cite

View full text Add to dashboard Cite

We report the synthesis of a family of D- and L-furano-D-apionucleosides, their 3'-deoxy, as well as their 2',3'-dideoxy analogues with thymine and adenine nucleobases. Single carbon homologation of 1,2-O-isopropylidene-D-glycero-tetrafuranos-3-ulose (15) and optimized glycosylation conditions involving microwave irradiation were key to the successful synthesis of the target compounds. While all target nucleosides failed to show significant antiviral activity, we demonstrated that the triphosphate of 2',3'-deoxy-D-apio-D-furanoadenosine (1), in contrast to that of its D-apio-L-furanose epimer 2, was readily incorporated into a DNA template by HIV reverse transcriptase to act as a DNA chain terminator. This led us to convert adenine derivative 1 into two phosphoramidate prodrugs. ProTide 9b was found active against HIV-1 and HIV-2 (EC50 = 0.5-1.5 μM), indicating that the lack of activity of the parent nucleoside, and possibly also other members of the D-apio-D-furanose nucleoside family must be sought in the inefficient cellular conversion to the monophosphate.

show abstract

Synthesis and Biological Activity of a Series of Methylene-Expanded Oxetanocin Nucleoside Analogues

Cited by 8 publications

References 0 publications

Synthesis of Conformationally North-Locked Pyrimidine Nucleosides Built on an Oxabicyclo[3.1.0]hexane Scaffold

Synthesis of Conformationally North-Locked Pyrimidine Nucleosides Built on an Oxabicyclo[3.1.0]hexane Scaffold

Synthesis and Reactions of 2-Chlorovinyl Sulfones

Synthesis of an Apionucleoside Family and Discovery of a Prodrug with Anti-HIV Activity

Contact Info

Product

Resources

About