Pub Date : 2016-01-29DOI: 10.1080/15257770.2015.1114129
Ran Xia, Li‐Ping Sun
ABSTRACT A convenient method for the regioselective synthesis of unsaturated nucleoside analogs in water under microwave irradiation was developed. All pyrimidine and purine nucleoside derivatives were exclusively alkylated at N1 and N9 respectively in good to excellent yields. In addition, this system could tolerate a broad range of functional groups, such as chloro, bromo, iodo, alkyl, amino, and hydroxyl groups. More importantly, the reaction scale could be enlarged to 50 mmol which made this route attractive for industrial application. GRAPHICAL ABSTRACT
{"title":"The Convenient Synthesis of Unsaturated Nucleoside Analogues in Water under Microwave Irradiation","authors":"Ran Xia, Li‐Ping Sun","doi":"10.1080/15257770.2015.1114129","DOIUrl":"https://doi.org/10.1080/15257770.2015.1114129","url":null,"abstract":"ABSTRACT A convenient method for the regioselective synthesis of unsaturated nucleoside analogs in water under microwave irradiation was developed. All pyrimidine and purine nucleoside derivatives were exclusively alkylated at N1 and N9 respectively in good to excellent yields. In addition, this system could tolerate a broad range of functional groups, such as chloro, bromo, iodo, alkyl, amino, and hydroxyl groups. More importantly, the reaction scale could be enlarged to 50 mmol which made this route attractive for industrial application. GRAPHICAL ABSTRACT","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"43 1","pages":"76 - 82"},"PeriodicalIF":0.0,"publicationDate":"2016-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86305220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-25DOI: 10.1080/15257770.2015.1114127
T. M. Barbosa, R. Rittner, Katie J Alexander, R. Cosstick, R. J. Abraham
ABSTRACT The guanine base in DNA, due to its low oxidation potential, is particularly sensitive to chemical modifications. A large number of guanine lesions have been characterized and studied in some detail due to their relationship with tissue inflammations. Nevertheless, one example of these lesions is the formation of 8-nitro-guanosine, but the NMR data of this compound was only partially interpreted. A comprehensive study of the two possible tautomeric forms, through a detailed characterization of this compound, has implications for its base pairing properties. The target compound was obtained through a synthetic sequence of five steps, where all intermediates were fully characterized using spectral data. The analysis of the two tautomers was then evaluated through NMR spectroscopy and theoretical calculations of the chemical shifts and NH coupling constants, which were also compared with the data from guanosine.
{"title":"Tautomerism in 8-Nitroguanosine Studied by NMR and Theoretical Calculations","authors":"T. M. Barbosa, R. Rittner, Katie J Alexander, R. Cosstick, R. J. Abraham","doi":"10.1080/15257770.2015.1114127","DOIUrl":"https://doi.org/10.1080/15257770.2015.1114127","url":null,"abstract":"ABSTRACT The guanine base in DNA, due to its low oxidation potential, is particularly sensitive to chemical modifications. A large number of guanine lesions have been characterized and studied in some detail due to their relationship with tissue inflammations. Nevertheless, one example of these lesions is the formation of 8-nitro-guanosine, but the NMR data of this compound was only partially interpreted. A comprehensive study of the two possible tautomeric forms, through a detailed characterization of this compound, has implications for its base pairing properties. The target compound was obtained through a synthetic sequence of five steps, where all intermediates were fully characterized using spectral data. The analysis of the two tautomers was then evaluated through NMR spectroscopy and theoretical calculations of the chemical shifts and NH coupling constants, which were also compared with the data from guanosine.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"17 1","pages":"53 - 63"},"PeriodicalIF":0.0,"publicationDate":"2016-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82476103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-02DOI: 10.1080/15257770.2015.1109098
M. Aouad
ABSTRACT The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9–11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et3N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K2CO3 in DMF yielded the corresponding acyclonucleoside analogs 16–18 and 23–25. The isopropylidenes 19 and acetyl derivatives 26–28 of the products were also prepared. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs.
{"title":"Synthesis and Antimicrobial Screening of Novel Thioglycosides and Acyclonucleoside Analogs Carrying 1,2,3-Triazole and 1,3,4-Oxadiazole Moieties","authors":"M. Aouad","doi":"10.1080/15257770.2015.1109098","DOIUrl":"https://doi.org/10.1080/15257770.2015.1109098","url":null,"abstract":"ABSTRACT The solvent-free 1,3-dipolar cycloaddition reaction of dimethylacetylene dicarboxylate (1) with 2-chlorophenyl azide (2) afforded 1,2,3-triazole diester 3 that upon hydrazinolysis, furnished the corresponding bis-acid hydrazide 4. The treatment of compound 4 with carbon disulfide in a refluxing potassium hydroxide solution furnished the desired bis-1,3,4-oxadiazole-2-thione 5 tethered to a 1,2,3-triazole moiety. The respective SOx-glycosides 9–11 were obtained by glycosylation of bis-oxadiazole 5 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide (6), 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7), and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride (8) in dry acetone in the presence of Et3N, which acted as a base. However, alkylation of 5 with halogeno-alkanol 12 or 13, chloroglycerol 14, bromoethers 20 or 21, and epichlohydrin 22 in the presence of K2CO3 in DMF yielded the corresponding acyclonucleoside analogs 16–18 and 23–25. The isopropylidenes 19 and acetyl derivatives 26–28 of the products were also prepared. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, 2D NMR, and mass spectra. The compounds were screened for their antibacterial and antifungal activities. A number of the tested compounds exhibited significant antimicrobial activity compared to the reference drugs.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"32 1","pages":"1 - 15"},"PeriodicalIF":0.0,"publicationDate":"2016-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81859736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-02DOI: 10.1080/15257770.2015.1114124
H. El‐Sayed, S. A. Said, A. Moustafa, M. Baraka, Rimaa T Abdel-Kader
ABSTRACT Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, 1H, 13C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.
摘要以3-甲基-2-氧(硫氧)-1,2-二氢喹啉1a,b为原料，在K2CO3存在下，分别与α- d -葡萄糖吡喃基、α- d -半乳糖吡喃基和α- d -乳糖溴基糖苷化，然后用Et3N/H2O脱乙酰化，制备了几种O-和s -喹啉苷。此外，1a、b与4-溴乙酸丁酯、2-乙酰氧乙氧基甲基溴和3-氯丙醇的烷基化反应可得到相应的O-和s -环喹啉核苷。1b与氯乙酸反应，然后在Et3N/THF和氯甲酸乙酯存在下与磺胺和磺胺嘧啶缩合，分别得到相应的磺胺衍生物14和15。新化合物的结构通过IR、1H、13C NMR和微量分析得到了证实。体外筛选了部分化合物的抗肿瘤和抗真菌活性。
{"title":"Synthesis and Biological Evaluation of 2-Oxo/Thioxoquinoxaline and 2-Oxo/Thioxoquinoxaline-Based Nucleoside Analogues","authors":"H. El‐Sayed, S. A. Said, A. Moustafa, M. Baraka, Rimaa T Abdel-Kader","doi":"10.1080/15257770.2015.1114124","DOIUrl":"https://doi.org/10.1080/15257770.2015.1114124","url":null,"abstract":"ABSTRACT Several O- and S-quinoxaline glycosides have been prepared by glycosidation of 3-methyl-2-oxo(thioxo)-1,2-dihydroquinoxalines 1a,b with α-D-glucopyranosyl, α-D-galactopyranosyl, and α-D-lactosyl bromide in the presence of K2CO3 followed by deacetylation with Et3N/H2O. Furthermore, alkylation of 1a,b with 4-bromobutyl acetate, 2-acetoxyethoxymethyl bromide, and 3-chloropropanol afforded the corresponding O- and S-acycloquinoxaline nucleosides. Reaction of 1b with chloroacetic acid followed by condensation with sulfacetamide and sulfadiazine in the presence of Et3N/THF and ethyl chloroformate gave the corresponding sulfonamide derivatives 14 and 15, respectively. The structures of new compounds were confirmed by using IR, 1H, 13C NMR spectra and microanalysis. Some of these compounds were screened in vitro for antitumor and antifungal activities.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"1 1","pages":"16 - 31"},"PeriodicalIF":0.0,"publicationDate":"2016-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90856502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-02DOI: 10.1080/15257770.2015.1114126
Mohan Kasula, Ramakrishnamraju Samunuri, Harapriya Chakravarty, Chandralata Bal, M. Baba, A. Jha, Ashoke Sharon
ABSTRACT Carbocyclic nucleosides are considered as nucleoside mimetic having high therapeutic potentials, however diverse exploration is still limited due to their synthetic difficulties. The major challenges are associated with the preparation of new base and carbocyclic sugar key intermediates. The modified base may provide conformational advantage to achieve better nucleoside mimetics and may also help in increasing the drug-like properties. In this manuscript, we report the use of acetamidine hydrochloride to synthesize 6-methyl-4-amino-pyrazolo[3,4-d]pyrimidine base and regioselective synthesis of six new carbocyclic nucleosides (6a-f) for antiviral evaluation. Theoretical investigations were carried out on the basis of thermodynamic and kinetic stability using MM based energy optimizations and QM based transition state search for the significant regioselectivity, which was further experimentally analyzed by NOE and UV spectroscopy.
{"title":"Regioselective Synthesis of Pyrazolo[3,4-D]Pyrimidine Based Carbocyclic Nucleosides as Possible Antiviral Agent","authors":"Mohan Kasula, Ramakrishnamraju Samunuri, Harapriya Chakravarty, Chandralata Bal, M. Baba, A. Jha, Ashoke Sharon","doi":"10.1080/15257770.2015.1114126","DOIUrl":"https://doi.org/10.1080/15257770.2015.1114126","url":null,"abstract":"ABSTRACT Carbocyclic nucleosides are considered as nucleoside mimetic having high therapeutic potentials, however diverse exploration is still limited due to their synthetic difficulties. The major challenges are associated with the preparation of new base and carbocyclic sugar key intermediates. The modified base may provide conformational advantage to achieve better nucleoside mimetics and may also help in increasing the drug-like properties. In this manuscript, we report the use of acetamidine hydrochloride to synthesize 6-methyl-4-amino-pyrazolo[3,4-d]pyrimidine base and regioselective synthesis of six new carbocyclic nucleosides (6a-f) for antiviral evaluation. Theoretical investigations were carried out on the basis of thermodynamic and kinetic stability using MM based energy optimizations and QM based transition state search for the significant regioselectivity, which was further experimentally analyzed by NOE and UV spectroscopy.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"38 1","pages":"43 - 52"},"PeriodicalIF":0.0,"publicationDate":"2016-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74130254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-01-02DOI: 10.1080/15257770.2015.1114125
Y. Tarasenko, T. Abramova, Viktor I Mamatuk, V. Silnikov
ABSTRACT Morpholino nucleoside triphosphates (A, U, G, C, T) bearing the active functional amino group tethered to morpholine residue and their fluorescently labeled derivatives were synthesized. All compounds were characterized by 1H, 13C, and 31P NMR, and mass spectrometry. A possibility of using fluorescently labeled morpholino nucleoside triphosphates as chain terminators in DNA sequencing is discussed.
合成了具有活性官能团基团的三磷酸Morpholino核苷(A, U, G, C, T)及其荧光标记衍生物。所有化合物均通过1H, 13C, 31P NMR和质谱进行了表征。讨论了在DNA测序中使用荧光标记的morpholino核苷三磷酸作为链终止物的可能性。
{"title":"Effective Synthesis of Fluorescently Labeled Morpholino Nucleoside Triphosphate Derivatives","authors":"Y. Tarasenko, T. Abramova, Viktor I Mamatuk, V. Silnikov","doi":"10.1080/15257770.2015.1114125","DOIUrl":"https://doi.org/10.1080/15257770.2015.1114125","url":null,"abstract":"ABSTRACT Morpholino nucleoside triphosphates (A, U, G, C, T) bearing the active functional amino group tethered to morpholine residue and their fluorescently labeled derivatives were synthesized. All compounds were characterized by 1H, 13C, and 31P NMR, and mass spectrometry. A possibility of using fluorescently labeled morpholino nucleoside triphosphates as chain terminators in DNA sequencing is discussed.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"2001 1","pages":"32 - 42"},"PeriodicalIF":0.0,"publicationDate":"2016-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86592798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-11-17DOI: 10.1080/15257770.2015.1088160
Takenori Dairaku, Kyoko Furuita, Hajime Sato, Y. Kondo, C. Kojima, A. Ono, Yoshiyuki Tanaka
Recently, we discovered novel silver(I)-mediated cytosine–cytosine base pair (C–AgI–C) in DNA duplexes. To understand the properties of these base pairs, we searched for a DNA sequence that can be used in NMR structure determination. After extensive sequence optimizations, a non-symmetric 15-base-paired DNA duplex with a single C–AgI–C base pair flanked by 14 A–T base pairs was selected. In spite of its challenging length for NMR measurements (30 independent residues) with small sequence variation, we could assign most non-exchangeable protons (254 out of 270) and imino protons for structure determination.
{"title":"Exploring a DNA Sequence for the Three-Dimensional Structure Determination of a Silver(I)-Mediated C-C Base Pair in a DNA Duplex By 1H NMR Spectroscopy","authors":"Takenori Dairaku, Kyoko Furuita, Hajime Sato, Y. Kondo, C. Kojima, A. Ono, Yoshiyuki Tanaka","doi":"10.1080/15257770.2015.1088160","DOIUrl":"https://doi.org/10.1080/15257770.2015.1088160","url":null,"abstract":"Recently, we discovered novel silver(I)-mediated cytosine–cytosine base pair (C–AgI–C) in DNA duplexes. To understand the properties of these base pairs, we searched for a DNA sequence that can be used in NMR structure determination. After extensive sequence optimizations, a non-symmetric 15-base-paired DNA duplex with a single C–AgI–C base pair flanked by 14 A–T base pairs was selected. In spite of its challenging length for NMR measurements (30 independent residues) with small sequence variation, we could assign most non-exchangeable protons (254 out of 270) and imino protons for structure determination.","PeriodicalId":19306,"journal":{"name":"Nucleosides, Nucleotides and Nucleic Acids","volume":"27 1","pages":"877 - 900"},"PeriodicalIF":0.0,"publicationDate":"2015-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84652794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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