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Frank Seela - One of the best experts on this subject based on the ideXlab platform.
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glycosylation of pyrrolo 2 3 d pyrimidines with 1 o acetyl 2 3 5 tri o benzoyl β d ribofuranose substituents and protecting groups effecting the synthesis of 7 deazapurine ribonucleosides
Journal of Organic Chemistry, 2018Co-Authors: Sachin A Ingale, Peter Leonard, Frank SeelaAbstract:Glycosylation of nonfunctionalized 6-chloro-7-deazapurine with commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose (45%) followed by amination and deprotection gave Tubercidin in only two steps. Similar conditions applied for the synthesis of 7-deazaguanosine employing pivaloylated 2-amino-6-chloro-7-deazapurine gave 18% glycosylation yield. The less bulky isobutyryl or acetyl protected amino group directed the glycosylation toward the exocyclic amino substituent. 7-Halogenated intermediates were glycosylated followed by dehalogenation to overcome the low glycosylation yield in the synthesis of 7-deazaguanosine.
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Glycosylation of Pyrrolo[2,3‑d]pyrimidines with 1‑O‑Acetyl-2,3,5-tri‑O‑benzoyl-β‑d‑ribofuranose: Substituents and Protecting Groups Effecting the Synthesis of 7‑Deazapurine Ribonucleosides
2018Co-Authors: Sachin A Ingale, Peter Leonard, Frank SeelaAbstract:Glycosylation of nonfunctionalized 6-chloro-7-deazapurine with commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose (45%) followed by amination and deprotection gave Tubercidin in only two steps. Similar conditions applied for the synthesis of 7-deazaguanosine employing pivaloylated 2-amino-6-chloro-7-deazapurine gave 18% glycosylation yield. The less bulky isobutyryl or acetyl protected amino group directed the glycosylation toward the exocyclic amino substituent. 7-Halogenated intermediates were glycosylated followed by dehalogenation to overcome the low glycosylation yield in the synthesis of 7-deazaguanosine
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7 functionalized 7 deazapurine β d and β l ribonucleosides related to Tubercidin and 7 deazainosine glycosylation of pyrrolo 2 3 d pyrimidines with 1 o acetyl 2 3 5 tri o benzoyl β d or β l ribofuranose
Tetrahedron, 2007Co-Authors: Frank Seela, Xin MingAbstract:Abstract Several 7-functionalized 7-deazapurine ribonucleosides were prepared. Glycosylation of 7-halogenated 6-chloro-7-deazapurines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β- d -ribofuranose or 1-O-acetyl-2,3,5-tri-O-benzoyl-β- l -ribofuranose gave the protected β- d -nucleosides 8c–e (53–62%) and the β- l -nucleosides 9b–e (57–72%), which were transformed to 7-halogenated 7-deazapurine ribonucleosides related to Tubercidin and 7-deazainosine. 7-Alkynyl derivatives (1f,g) and (2f,g) were obtained from the 7-iodo nucleosides 1e and 2e employing the palladium-catalyzed Sonogashira cross-coupling reaction. Within the series of 7-deazaadenosine (Tubercidin) analogues and 7-deazainosine derivatives physical data such as pKa values, chromatographic mobilities, 13C NMR chemical shifts were determined and correlated to each other.
Lesly A. Temesvari - One of the best experts on this subject based on the ideXlab platform.
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A Genome-Wide Over-Expression Screen Identifies Genes Involved in Phagocytosis in the Human Protozoan Parasite, Entamoeba histolytica
2016Co-Authors: Ada V. King, Brenda H. Welter, Amrita B. Koushik, Lindsay N. Gordon, Lesly A. TemesvariAbstract:Functional genomics and forward genetics seek to assign function to all known genes in a genome. Entamoeba histolytica is a protozoan parasite for which forward genetics approaches have not been extensively applied. It is the causative agent of amoebic dysentery and liver abscess, and infection is prevalent in developing countries that cannot prevent its fecal-oral spread. It is responsible for considerable global morbidity and mortality. Given that the E. histolytica genome has been sequenced, it should be possible to apply genomic approaches to discover gene function. We used a genome-wide over-expression screen to uncover genes regulating an important virulence function of E. histolytica, namely phagocytosis. We developed an episomal E. histolytica cDNA over-expression library, transfected the collection of plasmids into trophozoites, and applied a high-throughput screen to identify phagocytosis mutants in the population of over-expressing cells. The screen was based on the phagocytic uptake of human red blood cells loaded with the metabolic toxin, Tubercidin. Expression plasmids were isolated from trophozoites that survived exposure to Tubercidin-charged erythrocytes (phagocytosis mutants), and the cDNAs were sequenced. We isolated the gene encoding profilin, a well-characterized cytoskeleton-regulating protein with a known role in phagocytosis. This supports the validity of our approach. Furthermore, we assigned a phagocytic role to several genes not previously known to function in this manner. To our knowledge, this is the first genome-wide forward genetics screen to be applied to this pathogen. The study demonstrates the power o
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Tubercidin-loaded erythrocytes are less toxic to E. histolytic cells over-expressing H644 or EhLimA.
2013Co-Authors: Ada V. King, Brenda H. Welter, Amrita B. Koushik, Lindsay N. Gordon, Lesly A. TemesvariAbstract:Transgenic trophozoites were exposed to Tubercidin-loaded erythrocytes (3 treatments) and viability was assessed 48 hours after treatments. The data are reported as a percent of the starting number of viable amoebae before treatment. The data represent the mean ± S.D of 3 trials. E. histolytica transgenic cells exposed to Tubercidin-charged hRBCs displayed increased survival as compared to untransfected wild-type (WT) cells.
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Isolation of cDNAs from E. histolytica over-expressors without (Control) and with (Selected) selection with Tubercidin-charged erythrocytes.
2013Co-Authors: Ada V. King, Brenda H. Welter, Amrita B. Koushik, Lindsay N. Gordon, Lesly A. TemesvariAbstract:Isolation of cDNAs from E. histolytica over-expressors without (Control) and with (Selected) selection with Tubercidin-charged erythrocytes.
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Tubercidin-loaded erythrocytes are less toxic to an E. histolytica cell line with a phagocytosis defect.
2013Co-Authors: Ada V. King, Brenda H. Welter, Amrita B. Koushik, Lindsay N. Gordon, Lesly A. TemesvariAbstract:Trophozoites over-expressing a GFP-tagged version of a pleckstrin homology (PH) domain from mammalian Bruton’s tyrosine kinase (GFP-PHBtk), which exhibit reduced phagocytosis [22] or a control cell line over-expressing GFP alone (GFP) were exposed to Tubercidin-loaded erythrocytes three times and viability was assessed 48 hours after treatment. The data are reported as a percent of the starting number of viable amoebae before treatment. The data represent the mean ± S.D of 3 trials. The phagocytic mutant was insensitive to treatment with Tubercidin-charged hRBCs as evidenced by >100% survival (growth) in the presence of selection. This indicates that the selection scheme may be used to enrich for phagocytosis mutants from a population of cells.
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Tubercidin-loaded erythrocytes are toxic to E. histolytica.
2013Co-Authors: Ada V. King, Brenda H. Welter, Amrita B. Koushik, Lindsay N. Gordon, Lesly A. TemesvariAbstract:Trophozoites were exposed to Tubercidin-loaded erythrocytes two or three times (# of Treatments) and viability was assessed 24 hours or 48 hours after treatment. The data are reported as a percent of the starting number of viable amoebae before treatment. The data represent the mean ± S.D of ≥3 trials (***P
Sachin A Ingale - One of the best experts on this subject based on the ideXlab platform.
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glycosylation of pyrrolo 2 3 d pyrimidines with 1 o acetyl 2 3 5 tri o benzoyl β d ribofuranose substituents and protecting groups effecting the synthesis of 7 deazapurine ribonucleosides
Journal of Organic Chemistry, 2018Co-Authors: Sachin A Ingale, Peter Leonard, Frank SeelaAbstract:Glycosylation of nonfunctionalized 6-chloro-7-deazapurine with commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose (45%) followed by amination and deprotection gave Tubercidin in only two steps. Similar conditions applied for the synthesis of 7-deazaguanosine employing pivaloylated 2-amino-6-chloro-7-deazapurine gave 18% glycosylation yield. The less bulky isobutyryl or acetyl protected amino group directed the glycosylation toward the exocyclic amino substituent. 7-Halogenated intermediates were glycosylated followed by dehalogenation to overcome the low glycosylation yield in the synthesis of 7-deazaguanosine.
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Glycosylation of Pyrrolo[2,3‑d]pyrimidines with 1‑O‑Acetyl-2,3,5-tri‑O‑benzoyl-β‑d‑ribofuranose: Substituents and Protecting Groups Effecting the Synthesis of 7‑Deazapurine Ribonucleosides
2018Co-Authors: Sachin A Ingale, Peter Leonard, Frank SeelaAbstract:Glycosylation of nonfunctionalized 6-chloro-7-deazapurine with commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose (45%) followed by amination and deprotection gave Tubercidin in only two steps. Similar conditions applied for the synthesis of 7-deazaguanosine employing pivaloylated 2-amino-6-chloro-7-deazapurine gave 18% glycosylation yield. The less bulky isobutyryl or acetyl protected amino group directed the glycosylation toward the exocyclic amino substituent. 7-Halogenated intermediates were glycosylated followed by dehalogenation to overcome the low glycosylation yield in the synthesis of 7-deazaguanosine
Silvia Vertuani - One of the best experts on this subject based on the ideXlab platform.
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7 deazainosine derivatives synthesis and characterization of 7 and 7 8 substituted pyrrolo 2 3 d pyrimidine ribonucleosides
Nucleosides Nucleotides & Nucleic Acids, 2008Co-Authors: Nunzia Ciliberti, Elisa Durini, Stefano Manfredini, Silvia VertuaniAbstract:The synthesis of model 7 deazapurine derivatives related to Tubercidin and toyocamycin has been performed. Tubercidin derivatives were obtained by simple conversion of the amino group of the heterocyclic moiety of the starting 7-deazadenosine compounds, into a hydroxyl group. Preparation of toyocamycin derivatives was accomplished by treatment of the silylated 6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-4-one with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-d-ribofuranose. The glycosylation reaction afforded a mixture of 8-bromo 7-cyano 2′,3′,5′ tri-O-benzoyl 7-deazainosine and 6-bromo-5-cyano-3-(2′,3′,5′-tri-O-benzoyl-β-d-ribofuranosyl)pyrrolo[2,3-d]-pyrimidin-4-one isomers: The structures were assigned on the basis of NMR spectroscopy studies. Next deprotection treatment gave the novel 7-deazainosine ribonucleosides.
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7-Deazainosine derivatives: synthesis and characterization of 7-and 7,8-substituted pyrrolo[2,3-d]pyrimidine nucleosides
'Informa UK Limited', 2008Co-Authors: Nunzia Ciliberti, Elisa Durini, Stefano Manfredini, Silvia VertuaniAbstract:The synthesis of model 7 deazapurine derivatives related to Tubercidin and toyocamycin has been performed. Tubercidin derivatives were obtained by simple conversion of the amino group of the heterocyclic moiety of the starting 7-deazadenosine compounds, into hydroxyl group. Preparation of toyocamycin derivatives was accomplished by treatment of the silylated 6-bromo-5-cyanopyrrolo[2,3-d]pyrimidin-4-one with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose. The glycosylation reaction afforded a mixture of 7-ciano, 8-bromo, 2’,3’,5’ tri-O-benzoyl, 7-deazainosine and 6-bromo-5-cyano-3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)pyrrolo[2,3-d]-pyrimidin-4-one isomers: the structures were assigned on the basis of NMR spectroscopy studies. Next deprotection treatment gave the novel 7-deazainosine ribonucleosides
Chong Sheng Yuan - One of the best experts on this subject based on the ideXlab platform.
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nucleic acid related compounds 74 synthesis and biological activity of 2 and 3 deoxy 2 and 3 methylenenucleoside analogues that function as mechanism based inhibitors of s adenosyl l homocysteine hydrolase and or ribonucleotide reductase
Journal of Medicinal Chemistry, 1992Co-Authors: Morris J. Robins, Vicente Samano, Weijian Zhang, Jan Balzarini, Erik De Clercq, Ronald T Borchardt, Younha Lee, Chong Sheng YuanAbstract:Treatment of 2-amino-6-chloro-9-(beta-D-ribofuranosyl)purine (21) with TBDMS chloride/imidazole/DMF gave a separable mixture of 5'-O, 2',5'-bis-O (22), 3',5'-bis-O (23), and 2',3',5'-tris-O-TBDMS derivatives. Oxidation of 22 and 23 with CrO3/pyridine/Ac2O, treatment of the respective ketonucleosides with methylenetriphenylphosphorane, and deprotection gave 2-amino-6-chloro-9-[3(and 2)-deoxy-3(and 2)-methylene- beta-D-erythro-pentofuranosyl]purines (28 and 37) that were converted into other 2-amino-6-substituted-purine analogues. Tubercidin was converted into 2'-deoxy-2'-methyleneTubercidin (49) by an analogous route. Inactivation of S-adenosyl-L-homocysteine hydrolase by 2'- and 3'-methyleneadenosine analogues was investigated. Mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and anticancer and antiviral activities of 2'(and 3')-deoxy-2'(and 3')-methylenenucleoside analogues are discussed.
