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dc.contributor.authorMusiyak, V. V.en
dc.contributor.authorNizova, I. A.en
dc.contributor.authorChulakov, E. N.en
dc.contributor.authorSadretdinova, L. S.en
dc.contributor.authorTumashov, A. A.en
dc.contributor.authorLevit, G. L.en
dc.contributor.authorKrasnov, V. P.en
dc.date.accessioned2021-08-31T15:07:19Z-
dc.date.available2021-08-31T15:07:19Z-
dc.date.issued2021-
dc.identifier.citationStereochemical aspects in the synthesis of novel N-(purin-6-yl)dipeptides as potential antimycobacterial agents / V. V. Musiyak, I. A. Nizova, E. N. Chulakov, et al. — DOI 10.1007/s00726-021-02958-0 // Amino Acids. — 2021. — Vol. 53. — Iss. 3. — P. 407-415.en
dc.identifier.issn9394451-
dc.identifier.otherFinal2
dc.identifier.otherAll Open Access, Bronze3
dc.identifier.otherhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85101238737&doi=10.1007%2fs00726-021-02958-0&partnerID=40&md5=1152b365b22c3f76b2fbab4e8fef0c53
dc.identifier.otherhttps://link.springer.com/content/pdf/10.1007/s00726-021-02958-0.pdfm
dc.identifier.urihttp://elar.urfu.ru/handle/10995/103077-
dc.description.abstractThe synthesis of purine conjugates with natural amino acids is one of the promising directions in search for novel therapeutic agents, including antimycobacterial agents. The purpose of this study was to synthesize N-(purin-6-yl)dipeptides containing the terminal fragment of (S)-glutamic acid. To obtain the target compounds, two synthetic routes were tested. The first of them is based on coupling of N-(purin-6-yl)-(S)-amino acids to dimethyl (S)-glutamate in the presence of carbodiimide coupling agent followed by the removal of ester groups. However, it turned out that this coupling process was accompanied by racemization of the chiral center of N-(purin-6-yl)-α-amino acids and in all cases led to mixtures of (S,S)- and (R,S)-diastereomers (6:4). Individual (S,S)-diastereomers were obtained using an alternative approach based on the nucleophilic substitution of chlorine in 6-chloropurine or 2-amino-6-chloropurine with corresponding dipeptides as nucleophiles. The enantiomeric purity of the target compounds was confirmed by chiral HPLC. To test the assumption that racemization of the chiral center of N-(purin-6-yl)-α-amino acids occurs with the participation of nitrogen atoms of the imidazole ring via the stage of formation of a chirally labile intermediate, we obtained such structural analogs of N-(purin-6-yl)-(S)-alanine as N-(9-benzylpurin-6-yl)-(S)-alanine and N-(7-deazapurin-6-yl)-(S)-alanine. It was found that coupling of these compounds to dimethyl (S)-glutamate was also accompanied by racemization. This indicates that the imidazole fragment does not play a crucial role in this process. When testing the antimycobacterial activity of some of the obtained compounds, conjugates with moderate activity against the laboratory Mycobacterium tuberculosis H37Rv strain (MIC 3.1–6.25 μg/mL) were identified. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, AT part of Springer Nature.en
dc.description.sponsorshipThe work was financially supported by the Russian Science Foundation (Grant 19-13-00231). We are grateful to Dr. Marionella A. Kravchenko [Ural Research Institute of Phthisiopulmonology (National Medical Research Center, Ministry of Healthcare of the Russian Federation, Ekaterinburg, Russia)] for conducting biological trials. Analytical studies were carried out using equipment of the Centre for Joint Use ?Spectroscopy and Analysis of Organic Compounds? at the Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences.en
dc.format.mimetypeapplication/pdfen
dc.language.isoenen
dc.publisherSpringeren
dc.relationinfo:eu-repo/grantAgreement/RSF//19-13-00231en
dc.rightsinfo:eu-repo/semantics/openAccessen
dc.sourceAmino Acids2
dc.sourceAmino Acidsen
dc.subjectANTIMYCOBACTERIAL ACTIVITYen
dc.subjectCOUPLINGen
dc.subjectDIPEPTIDESen
dc.subjectNUCLEOPHILIC SUBSTITUTIONen
dc.subjectPURINEen
dc.subjectRACEMIZATIONen
dc.subjectANTIMYCOBACTERIAL AGENTen
dc.subjectCYANAMIDEen
dc.subjectGLUTAMIC ACIDen
dc.subjectN(PURIN 6 YL)ALANINEen
dc.subjectN(PURIN 6 YL)DIPEPTIDEen
dc.subjectN(PURIN 6 YL)PHENYLALANINEen
dc.subjectN(PURIN 6 YL)VALINEen
dc.subjectUNCLASSIFIED DRUGen
dc.subjectANTIBACTERIAL ACTIVITYen
dc.subjectANTIMYCOBACTERIAL ACTIVITYen
dc.subjectARTICLEen
dc.subjectCHEMICAL REACTIONen
dc.subjectCONJUGATIONen
dc.subjectCOUPLING PROCESSen
dc.subjectDIASTEREOISOMERen
dc.subjectDRUG STRUCTUREen
dc.subjectDRUG SYNTHESISen
dc.subjectENANTIOMERen
dc.subjectHIGH PERFORMANCE LIQUID CHROMATOGRAPHYen
dc.subjectMINIMUM INHIBITORY CONCENTRATIONen
dc.subjectMYCOBACTERIUM TUBERCULOSISen
dc.subjectNONHUMANen
dc.subjectPRIORITY JOURNALen
dc.subjectRACEMIZATIONen
dc.subjectSTEREOCHEMISTRYen
dc.titleStereochemical aspects in the synthesis of novel N-(purin-6-yl)dipeptides as potential antimycobacterial agentsen
dc.typeArticleen
dc.typeinfo:eu-repo/semantics/articleen
dc.typeinfo:eu-repo/semantics/publishedVersionen
dc.identifier.doi10.1007/s00726-021-02958-0-
dc.identifier.scopus85101238737-
local.contributor.employeeMusiyak, V.V., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation
local.contributor.employeeNizova, I.A., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation
local.contributor.employeeChulakov, E.N., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation
local.contributor.employeeSadretdinova, L.S., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation
local.contributor.employeeTumashov, A.A., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation, Ural Federal University, 19, Mira St., Ekaterinburg, 620002, Russian Federation
local.contributor.employeeLevit, G.L., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation
local.contributor.employeeKrasnov, V.P., Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation, Ural Federal University, 19, Mira St., Ekaterinburg, 620002, Russian Federation
local.description.firstpage407-
local.description.lastpage415-
local.issue3-
local.volume53-
local.contributor.departmentPostovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20, S. Kovalevskoy/Akademicheskaya St., Ekaterinburg, 620108, Russian Federation
local.contributor.departmentUral Federal University, 19, Mira St., Ekaterinburg, 620002, Russian Federation
local.identifier.pure21031660-
local.identifier.pure08ce0a5f-8439-4b66-b6f9-91df51d579b6uuid
local.identifier.eid2-s2.0-85101238737-
local.fund.rsf19-13-00231-
local.identifier.pmid33599833-
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