An efficient synthesis tetrazole and oxadiazole analogues of novel 2′-deoxy-C-nucleosides and their antitumor activity (original) (raw)
Related papers
A short and efficient synthesis of 2′-deoxybenzo- and pyridoimidazole C-nucleosides
Tetrahedron Letters, 2003
A short route to a series of 2%-deoxy-C-nucleosides featuring substituted nucleobases has been developed. The key step is the formation of the cyclized products following Mukaiyama's type amide coupling and a simple dehydration, starting from readily accessible synthons. The epimerization of the C1%-stereogenic center was avoided under mild and controlled conditions.
The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. a b s t r a c t Drug resistance and emergence of new pathogens highlight the need for developing new therapeutic agents. We focused on 2-oxonicotinonitrile (2-ONN) as derivative of the natural product 2-pyridinone. 1 Herein, we describe the synthesis of 2-ONNs bearing two aryl groups, which we coupled with organo-halides, including three glycosyl bromides, to prepare the nucleoside analogues. Coupling occurred mostly at the 2-ONN ring nitrogen to give the aimed targets, and in a few cases, it happened at the 2-oxo position giving O-alkylation products. Free 2-ONNs and their acetylated nucleosides were tested against a number of viruses. The nucleoside analogue 2a Ac showed good anti SARS-CoV and anti influenza A (H 5 N 1) activities. Additionally, 7b had good activity against Gram positive bacterium, Bacillis subtilis.
Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues
Molecules, 2020
Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including gemcitabine and cytarabine, are the go-to option in first-line treatments. However, these materials do have limitations and the development of next generation compounds remains a topic of significant interest and necessity. Herein, we discuss recent advances in the chemical synthesis and biological evaluation of nucleoside analogues as potential anticancer agents. Focus is paid to 4′-heteroatom substitution of the furanose oxygen, 2′-, 3′-, 4′-and 5′-position ring modifications and the development of new prodrug strategies for these materials.
2023
The synthesis and antiproliferative evaluation of novel D-glucopyranuronamidecontaining nucleosides is described. Based on our previously reported anticancer Dglucuronamide-based nucleosides, new analogues comprising N/O-dodecyl or Npropargyl substituents at the glucuronamide unit and anomerically N-linked 2-acetamido-6-chloropurine, 6-chloropurine or 4-(6-chloropurinyl)methyl triazole motifs were synthesized in 4-6 steps starting from acetonide-protected glucofuranurono-6,3-lactone. The methodologies were based on the access to N-substituted glycopyranuronamide precursors, namely 1,2-O-acetyl derivatives or glucuronoamidyl azides for further Nglycosidation with a nucleobase or 1,3-dipolar cycloaddition with N 9 and N 7-propargyl-6-chloropurines, respectively. N-Propargyl glucuronamide-based N 9-linked purine nucleosides were converted into (triazolyl)methyl amide-6,6-linked pseudodisaccharide nucleosides via cycloaddition with methyl 6-azido glucopyranoside. A CuI/Amberlyst A-21 catalytic system employed in the cycloaddition reactions also effected conversion into 6-dimethylamino purine nucleosides. Antiproliferative evaluation in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells revealed significant effects exhibited by the synthesized monododecylated purine-containing nucleosides. A N-propargyl 3-Ododecyl glucuronamide derivative comprising a N 9-β-linked 6-chloropurine moiety was the most active compound against MCF-7 cells (GI50 = 11.9 μM) while a related α-(purinyl)methyltriazole nucleoside comprising a N 7-linked 6-chloropurine moiety exhibited the highest activity against K562 cells was (GI50 = 8.0 μM). Flow cytometry analysis and immunoblotting analysis of apoptosis-related proteins in K562 cells treated with the N-propargyl 3-O-dodecyl glucuronamide-based N 9-linked 6chloropurine nucleoside indicated that it acts via apoptosis induction.
Organic Letters, 2010
N-aryltriazole nucleosides are new chemical entities with potential biological activity. The two phosphor ligands, Synphos and Xantphos, had a selective and effective impact on Pd-catalyzed C-N coupling with the 5-and 3-bromotriazole acyclonucleoside isomers, affording the corresponding and otherwise difficult to achieve N-aryltriazole nucleosides with good to excellent yields. In addition, two of the synthesized nucleosides showed superior anticancer activity against drug-resistant pancreatic cancer, compared to the reference drug gemcitabine.
Carbohydrate Research, 2012
A new series of 4 0 -C-cyano and 4 0 -C-cyano-4 0 -deoxy pyrimidine pyranonucleosides has been designed and synthesized. Commercially available 1,2,3,4,6-penta-O-acetyl-D-mannopyranose (1) was condensed with silylated 5-fluorouracil, uracil, and thymine, respectively to afford after deacetylation 1-(a-D-mannopyranosyl)nucleosides (2a-c). Subjecting 2a-c to the sequence of specific acetalation, selective protection of the primary hydroxyl group and oxidation, the 4 0 -ketonucleosides 6a-c and 7c were obtained. Reaction of compounds 6a,b, and 7c with sodium cyanide and subsequent deprotection gave the target 1-(4 0 -Ccyano-a-D-mannopyranosyl)nucleosides 12a-c. Deoxygenation at the 4 0 -position of cyanohydrins 8a,b, and 11c followed by deprotection led to the desired 1-(4 0 -C-cyano-4 0 -deoxy-a-D-talopyranosyl)nucleosides (15a-c). The newly synthesized compounds were evaluated for their potential antiviral and cytostatic activities in cell culture.
New GLYCOSYL-(CARBOXAMIDE)-1,2,3-TRIAZOLE- N -Nucleosides: Synthesis and Antitumor Activity
Nucleosides, Nucleotides and Nucleic Acids, 2002
A series of potential bioactive compounds, 1-glucopyranosyl- 1,2,3-triazole-4,5-dimethylcarboxylate, 1-glucopyranosyl-1,2,3-triazole-4,5-N-dicarboxamide,-dialkyl-dicarboxamide-N-nucleosides and 6-amino-4H-1-(beta-D-glucopyranosyl)-8-hydroxy-1,2.3-triazolo[4,5-e][1,3]-diazepin-4-one, were synthesized. Primary activity screening of the novel nucleosides showed poor or no anticancer activity against breast, lung and CNS tumors.
Synthesis of benzimidazole nucleosides and their anticancer activity
Carbohydrate Research, 2020
An efficient route for the synthesis of benzimidazole nucleosides 1-8 from readily available D-glucose via 3,5dihydroxy-1,2-O-isopropylidene-α-D-ribofuranose and 3-azido-3-deoxy-1,2-O-isopropylidene-α-D-xylofuranose intermediates has been adopted. Ribofuranosyl nucleosides 1-4 with different benzimidazole bases, and 3ʹdeoxy-3ʹ-azido-ribofuranosyl nucleosides 5-8, as another series, were obtained. All these newly synthesized analogs were evaluated for anticancer activity using MDA-MB-231 cell line. Among the differently substituted derivatives, 3ʹ-azide substituted nucleosides (5-8) are more potent compared to ribofuranosyl analogs 1-4. The C-3ʹ-azido analog 8 having anthryl group at 2-position of nucleobase show almost similar potency as that of standard etoposide.