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Schuster"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>2\u2010Chloro\u20102\u2032\u2010deoxyadenosine (cladribine, <jats:bold>1<\/jats:bold>) was acylated with valproic acid (<jats:bold>2<\/jats:bold>) under various reaction conditions yielding 2\u2010chloro\u20102\u2032\u2010deoxy\u20103\u2032,5\u2032\u2010<jats:italic>O<\/jats:italic>\u2010divalproyladenosine (<jats:bold>3<\/jats:bold>) as well as the 3\u2032\u2010<jats:italic>O<\/jats:italic>\u2010 and 5\u2032\u2010<jats:italic>O<\/jats:italic>\u2010monovalproylated derivatives, 2\u2010chloro\u20102\u2032\u2010deoxy\u20103\u2032\u2010<jats:italic>O<\/jats:italic>\u2010valproyladenosine (<jats:bold>4<\/jats:bold>) and 2\u2010chloro\u20102\u2032\u2010deoxy\u20105\u2032\u2010<jats:italic>O<\/jats:italic>\u2010valproyladenosine (<jats:bold>5<\/jats:bold>), as new co\u2010drugs. In addition, 6\u2010azauridine\u20102\u2032,3\u2032\u2010<jats:italic>O<\/jats:italic>\u2010(ethyl levulinate) (<jats:bold>8<\/jats:bold>) was valproylated at the 5\u2032\u2010OH group (\u2192<jats:bold>9<\/jats:bold>). All products were characterized by <jats:sup>1<\/jats:sup>H\u2010 and <jats:sup>13<\/jats:sup>C\u2010NMR spectroscopy and ESI mass spectrometry. The structure of the by\u2010product <jats:bold>6<\/jats:bold> (<jats:italic>N<\/jats:italic>\u2010cyclohexyl\u2010<jats:italic>N<\/jats:italic>\u2010(cyclohexylcarbamoyl)\u20102\u2010propylpentanamide), formed upon valproylation of cladribine in the presence of <jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2010dimethylaminopyridine and dicyclohexylcarbodiimide, was analyzed by X\u2010ray crystallography. Cladribine as well as its valproylated co\u2010drugs were tested upon their cancerostatic\/cancerotoxic activity in human astrocytoma\/oligodendroglioma GOS\u20103 cells, in rat malignant neuro ectodermal BT4Ca cells, as well as in phorbol\u201012\u2010myristate 13\u2010acetate (PMA)\u2010differentiated human THP\u20101 macrophages. The most important result of these experiments is the finding that only the 3\u2032\u2010<jats:italic>O<\/jats:italic>\u2010valproylated derivative <jats:bold>4<\/jats:bold> exhibits a significant antitumor activity while the 5\u2032\u2010<jats:italic>O<\/jats:italic>\u2010 as well as the 3\u2032,5\u2032\u2010<jats:italic>O<\/jats:italic>\u2010divalproylated cladribine derivatives <jats:bold>3<\/jats:bold> and <jats:bold>5<\/jats:bold> proved to be inactive.<\/jats:p>","DOI":"10.1002\/cbdv.201800497","type":"journal-article","created":{"date-parts":[[2019,1,8]],"date-time":"2019-01-08T19:54:35Z","timestamp":1546977275000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis of New Potential Lipophilic Co\u2010Drugs of 2\u2010Chloro\u20102\u2032\u2010deoxyadenosine (Cladribine, 2\u2010CdA, Mavenclad\u00ae, Leustatin\u00ae) and 6\u2010Azauridine (z<sup>6<\/sup>U) with Valproic Acid"],"prefix":"10.1002","volume":"16","author":[{"given":"Christine","family":"Knies","sequence":"first","affiliation":[{"name":"Organic Chemistry I - Bioorganic Chemistry, Institute of Chemistry of New Materials University of Osnabr\u00fcck, Barbarastr. 7  D-49069 Osnabr\u00fcck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Reuter","sequence":"additional","affiliation":[{"name":"Anorganische Chemie II, Strukturchemie, Institute of Chemistry of New Materials University of Osnabr\u00fcck  Barbarastr. 7, D-49069 Osnabr\u00fcck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Hammerbacher","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Department of Medical Cell Biology Philipps-University of Marburg  Robert-Koch-Str. 8 D-35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Bender","sequence":"additional","affiliation":[{"name":"Organic Chemistry I - Bioorganic Chemistry, Institute of Chemistry of New Materials University of Osnabr\u00fcck, Barbarastr. 7  D-49069 Osnabr\u00fcck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel A.","family":"Bonaterra","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Department of Medical Cell Biology Philipps-University of Marburg  Robert-Koch-Str. 8 D-35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Kinscherf","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Department of Medical Cell Biology Philipps-University of Marburg  Robert-Koch-Str. 8 D-35032 Marburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3968-496X","authenticated-orcid":false,"given":"Helmut","family":"Rosemeyer","sequence":"additional","affiliation":[{"name":"Organic Chemistry I - Bioorganic Chemistry, Institute of Chemistry of New Materials University of Osnabr\u00fcck, Barbarastr. 7  D-49069 Osnabr\u00fcck Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,25]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"crossref","unstructured":"M.-C. 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