3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine
1-Deazatubercidin (5) has been synthesized by glycosylation of the anion of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (9) with 1-chloro-2,3-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-alpha-D-r ibofuranos e (12). The reaction gave a mixture of blocked nucleosides with beta- and alpha-configuration (...
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| Veröffentlicht in: | Journal of medicinal chemistry 1989-07, Vol.32 (7), p.1463-1466 |
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| creator | Cristalli, Gloria Franchetti, Palmarisa Grifantini, M Nocentini, Giuseppe Vittori, Sauro |
| description | 1-Deazatubercidin (5) has been synthesized by glycosylation of the anion of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (9) with 1-chloro-2,3-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-alpha-D-r ibofuranos e (12). The reaction gave a mixture of blocked nucleosides with beta- and alpha-configuration (13a and 13b). Deprotection of 13a provided 4,6-dichloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (14), which on treatment with hydrazine, followed by reduction of the resulting 4-hydrazino compound with Raney nickel, gave 4-amino-6-chloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (15), 1-deazatubercidin, and a small quantity of 4,6-diamino-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (16). Dehalogenation of 15 provided another route to 5. 2-Chloro-2'-deoxy-3,7-dideazaadenosine (6) together with 2'-deoxy-3,7-dideazaadenosine (18) was obtained by hydrazinolysis of 4,6-dichloro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo- [3,2-c]pyridine (17), followed by reduction of the resulting 4-hydrazino compound. Nucleosides 5, 6, 15, and 18 are devoid of any significant antitumor activity in vitro. Compound 16 showed significant activity against P388 leukemia in cell culture. |
| doi_str_mv | 10.1021/jm00127a011 |
| format | Article |
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Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine</title><source>MEDLINE</source><source>ACS Publications</source><creator>Cristalli, Gloria ; Franchetti, Palmarisa ; Grifantini, M ; Nocentini, Giuseppe ; Vittori, Sauro</creator><creatorcontrib>Cristalli, Gloria ; Franchetti, Palmarisa ; Grifantini, M ; Nocentini, Giuseppe ; Vittori, Sauro</creatorcontrib><description>1-Deazatubercidin (5) has been synthesized by glycosylation of the anion of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (9) with 1-chloro-2,3-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-alpha-D-r ibofuranos e (12). The reaction gave a mixture of blocked nucleosides with beta- and alpha-configuration (13a and 13b). Deprotection of 13a provided 4,6-dichloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (14), which on treatment with hydrazine, followed by reduction of the resulting 4-hydrazino compound with Raney nickel, gave 4-amino-6-chloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (15), 1-deazatubercidin, and a small quantity of 4,6-diamino-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (16). Dehalogenation of 15 provided another route to 5. 2-Chloro-2'-deoxy-3,7-dideazaadenosine (6) together with 2'-deoxy-3,7-dideazaadenosine (18) was obtained by hydrazinolysis of 4,6-dichloro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo- [3,2-c]pyridine (17), followed by reduction of the resulting 4-hydrazino compound. Nucleosides 5, 6, 15, and 18 are devoid of any significant antitumor activity in vitro. Compound 16 showed significant activity against P388 leukemia in cell culture.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00127a011</identifier><identifier>PMID: 2641872</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Aminoglycosides ; Animals ; Anti-Bacterial Agents - chemical synthesis ; Antineoplastic Agents - chemical synthesis ; Carbohydrates. Nucleosides and nucleotides ; Carcinoma, Squamous Cell - pathology ; Chemical Phenomena ; Chemistry ; Exact sciences and technology ; Humans ; Leukemia L1210 - pathology ; Leukemia P388 - pathology ; Leukemia, Promyelocytic, Acute - pathology ; Mice ; Nucleosides, nucleotides and oligonucleotides ; Organic chemistry ; Preparations and properties ; Tubercidin - analogs & derivatives ; Tubercidin - chemical synthesis ; Tubercidin - pharmacology ; Tumor Cells, Cultured - drug effects</subject><ispartof>Journal of medicinal chemistry, 1989-07, Vol.32 (7), p.1463-1466</ispartof><rights>1991 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a415t-ee217e9b1a6d0aeb0bb16cb5fe6dd8533f3ceeda1a9a9df1e2187125faba358d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00127a011$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00127a011$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,778,782,2754,27059,27907,27908,56721,56771</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19486863$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2641872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cristalli, Gloria</creatorcontrib><creatorcontrib>Franchetti, Palmarisa</creatorcontrib><creatorcontrib>Grifantini, M</creatorcontrib><creatorcontrib>Nocentini, Giuseppe</creatorcontrib><creatorcontrib>Vittori, Sauro</creatorcontrib><title>3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>1-Deazatubercidin (5) has been synthesized by glycosylation of the anion of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (9) with 1-chloro-2,3-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-alpha-D-r ibofuranos e (12). The reaction gave a mixture of blocked nucleosides with beta- and alpha-configuration (13a and 13b). Deprotection of 13a provided 4,6-dichloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (14), which on treatment with hydrazine, followed by reduction of the resulting 4-hydrazino compound with Raney nickel, gave 4-amino-6-chloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (15), 1-deazatubercidin, and a small quantity of 4,6-diamino-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (16). Dehalogenation of 15 provided another route to 5. 2-Chloro-2'-deoxy-3,7-dideazaadenosine (6) together with 2'-deoxy-3,7-dideazaadenosine (18) was obtained by hydrazinolysis of 4,6-dichloro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo- [3,2-c]pyridine (17), followed by reduction of the resulting 4-hydrazino compound. Nucleosides 5, 6, 15, and 18 are devoid of any significant antitumor activity in vitro. Compound 16 showed significant activity against P388 leukemia in cell culture.</description><subject>Aminoglycosides</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Carbohydrates. Nucleosides and nucleotides</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Chemical Phenomena</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Humans</subject><subject>Leukemia L1210 - pathology</subject><subject>Leukemia P388 - pathology</subject><subject>Leukemia, Promyelocytic, Acute - pathology</subject><subject>Mice</subject><subject>Nucleosides, nucleotides and oligonucleotides</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Tubercidin - analogs & derivatives</subject><subject>Tubercidin - chemical synthesis</subject><subject>Tubercidin - pharmacology</subject><subject>Tumor Cells, Cultured - drug effects</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhS0EKkNhxRopG-gCXPxI7GSJyluVqJgiJDbWjX2jekicqZ2gDhv-Om4zKiyQWFhX8vnuOZYPIY85O-ZM8JebgTEuNDDO75AVrwSjZc3Ku2TFmBBUKCHvkwcpbRhjkgt5QA6EKnmtxYr8ki80fe0dwk_YztEHLMJsexxTvkvHxXoXpgtMPhUQXD6Tn-ZhjAXYyf_w064Yu4LTm_VpbjFa73y4YQW1F_0YRyqOsj5e7eh1lFuiwGHIEQEfknsd9Akf7ech-fL2zfnJe3r66d2Hk1enFEpeTRRRcI1Ny0E5BtiytuXKtlWHyrm6krKTFtEBhwYa1_GM15qLqoMWZFU7eUieLb7bOF7OmCYz-GSx7yHgOCejG1ZpVYn_grxSNdMNz-DzBbRxTCliZ7bRDxB3hjNz3Yv5q5dMP9nbzu2A7pbdF5H1p3sdkoW-ixCsT38sm7JWtZKZowvn04RXtzrE70ZpqStzfrY26_qzUB-_nZmvmT9aeLDJbMY5hvzL_3zhbx9jsi8</recordid><startdate>19890701</startdate><enddate>19890701</enddate><creator>Cristalli, Gloria</creator><creator>Franchetti, Palmarisa</creator><creator>Grifantini, M</creator><creator>Nocentini, Giuseppe</creator><creator>Vittori, Sauro</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>19890701</creationdate><title>3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine</title><author>Cristalli, Gloria ; Franchetti, Palmarisa ; Grifantini, M ; Nocentini, Giuseppe ; Vittori, Sauro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a415t-ee217e9b1a6d0aeb0bb16cb5fe6dd8533f3ceeda1a9a9df1e2187125faba358d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Aminoglycosides</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Carbohydrates. Nucleosides and nucleotides</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Chemical Phenomena</topic><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>Humans</topic><topic>Leukemia L1210 - pathology</topic><topic>Leukemia P388 - pathology</topic><topic>Leukemia, Promyelocytic, Acute - pathology</topic><topic>Mice</topic><topic>Nucleosides, nucleotides and oligonucleotides</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Tubercidin - analogs & derivatives</topic><topic>Tubercidin - chemical synthesis</topic><topic>Tubercidin - pharmacology</topic><topic>Tumor Cells, Cultured - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cristalli, Gloria</creatorcontrib><creatorcontrib>Franchetti, Palmarisa</creatorcontrib><creatorcontrib>Grifantini, M</creatorcontrib><creatorcontrib>Nocentini, Giuseppe</creatorcontrib><creatorcontrib>Vittori, Sauro</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cristalli, Gloria</au><au>Franchetti, Palmarisa</au><au>Grifantini, M</au><au>Nocentini, Giuseppe</au><au>Vittori, Sauro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1989-07-01</date><risdate>1989</risdate><volume>32</volume><issue>7</issue><spage>1463</spage><epage>1466</epage><pages>1463-1466</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>1-Deazatubercidin (5) has been synthesized by glycosylation of the anion of 4,6-dichloro-1H-pyrrolo[3,2-c]pyridine (9) with 1-chloro-2,3-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-alpha-D-r ibofuranos e (12). The reaction gave a mixture of blocked nucleosides with beta- and alpha-configuration (13a and 13b). Deprotection of 13a provided 4,6-dichloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (14), which on treatment with hydrazine, followed by reduction of the resulting 4-hydrazino compound with Raney nickel, gave 4-amino-6-chloro-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (15), 1-deazatubercidin, and a small quantity of 4,6-diamino-1-beta-D-ribofuranosylpyrrolo[3,2-c]pyridine (16). Dehalogenation of 15 provided another route to 5. 2-Chloro-2'-deoxy-3,7-dideazaadenosine (6) together with 2'-deoxy-3,7-dideazaadenosine (18) was obtained by hydrazinolysis of 4,6-dichloro-1-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo- [3,2-c]pyridine (17), followed by reduction of the resulting 4-hydrazino compound. Nucleosides 5, 6, 15, and 18 are devoid of any significant antitumor activity in vitro. Compound 16 showed significant activity against P388 leukemia in cell culture.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>2641872</pmid><doi>10.1021/jm00127a011</doi><tpages>4</tpages></addata></record> |
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| subjects | Aminoglycosides Animals Anti-Bacterial Agents - chemical synthesis Antineoplastic Agents - chemical synthesis Carbohydrates. Nucleosides and nucleotides Carcinoma, Squamous Cell - pathology Chemical Phenomena Chemistry Exact sciences and technology Humans Leukemia L1210 - pathology Leukemia P388 - pathology Leukemia, Promyelocytic, Acute - pathology Mice Nucleosides, nucleotides and oligonucleotides Organic chemistry Preparations and properties Tubercidin - analogs & derivatives Tubercidin - chemical synthesis Tubercidin - pharmacology Tumor Cells, Cultured - drug effects |
| title | 3,7-Dideazapurine nucleosides. Synthesis and antitumor activity of 1-deazatubercidin and 2-chloro-2'-deoxy-3,7-dideazaadenosine |
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