Synthesis of 4′/5′-Spirocyclopropanated Uridine and <scp>d</scp>-Xylouridine Derivatives and Their Activity against the Human Respiratory Syncytial Virus

Köllmann, Christoph; Wiechert, Svenja M; Jones, Peter G.; Pietschmann, Thomas; Werz, Daniel B.

doi:10.1021/acs.orglett.9b02555

Cited by 22 publications

(19 citation statements)

References 43 publications

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“…[1][2][3][4] Particularly common are 1,1-disubstituted cyclopropanes. [5][6][7][8][9][10] The two substituents are placed in a dened spacial arrangement to each other and the synthesis of such compounds is straightforward, as there is no additional chirality associated with the cyclopropane ring. In recent years more elaborate chiral cyclopropanes have been incorporated into therapeutic scaffolds, such as the trisubstituted cyclopropanes in beclabuvir (1), 11 paritaprevir (2) 12,13 and glecaprevir (3) [14][15][16] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

et al. 2021

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“…In the case of spirocyclopropanes bound to heterocycles there are few reports of biological activity. Those that can be found are limited to documenting the antiviral activity [ 27 , 28 ], and their activity as inhibitors of spliceosome [ 29 ], alpha- l -fucosidase [ 30 ], β-lactamase [ 31 ] and non-nucleoside inhibitors of HIV-1 reverse transcriptase [ 32 ]. Of note, ledipasvir is used to treat hepatitis C and has this structural element [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

et al. 2021

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This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models—S. cerevisiae, five cancer cell lines, and the parasite L. mexicana—were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

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“…As described in the Introduction section, exo -glycals have been used as versatile precursors for the synthesis of various compounds through modifications of the exocyclic CC bonds. To elucidate the effect of the chiral ribose moiety on the stereochemistry of exo -CC modifications, ( E )- 5a and ( Z )- 5a were subjected to the Simmons–Smith–Furukawa reaction . The cyclopropanation occurred exclusively from the α-face to afford 11 and its epimer ( epi - 11 ) from ( E )- 5a and ( Z )- 5a , respectively (Schemes and ).…”

Section: Results and Discussionmentioning

confidence: 99%

Stereoselective Synthesis of Ribofuranoid exo-Glycals by One-Pot Julia Olefination Using Ribofuranosyl Sulfones

Oka

Mori²,

Suzuki³

et al. 2020

J. Org. Chem.

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One-pot Julia olefination using ribofuranosyl sulfones is described. The α-anomers of the ribofuranosyl sulfones were synthesized with complete α-selectivity via the glycosylation of heteroarylthiols using ribofuranosyl iodides as glycosyl donors and the subsequent oxidation of the resulting heteroaryl 1-thioribofuranosides with magnesium monoperphthalate (MMPP). The Julia olefination of the α-ribofuranosyl sulfones with aldehydes proceeded smoothly in one pot to afford the thermodynamically less stable (E)-exo-glycals with modest-to-excellent stereoselectivity (up to E/Z = 94:6) under the optimized conditions. The E selectivity was especially high for aromatic aldehydes. In contrast, the (Z)-exo-glycal was obtained as the main product with low stereoselectivity when the corresponding β-ribofuranosyl sulfone was used (E/Z = 41:59). The remarkable impact of the anomeric configuration of the ribofuranosyl sulfones on the stereoselectivity of the Julia olefination has been rationalized using density functional theory (DFT) calculations. The protected ribose moiety of the resulting exo-glycals induced completely α-selective cyclopropanation on the exocyclic carbon–carbon double bond via the Simmons–Smith–Furukawa reaction. The 2-cyanoethyl group was found to be useful for the protection of the exo-glycals, as it could be removed without affecting the exocyclic CC bond.

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Synthesis of 4′/5′-Spirocyclopropanated Uridine and d-Xylouridine Derivatives and Their Activity against the Human Respiratory Syncytial Virus

Cited by 22 publications

References 43 publications

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis

Stereoselective Synthesis of Ribofuranoid exo-Glycals by One-Pot Julia Olefination Using Ribofuranosyl Sulfones

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