Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal
A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied...
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| Veröffentlicht in: | Journal of organic chemistry 2016-11, Vol.81 (21), p.10236-10241 |
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| container_end_page | 10241 |
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| container_issue | 21 |
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| container_title | Journal of organic chemistry |
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| creator | Ali, Sajjad Yu, Shun-Ming Yao, Zhu-Jun |
| description | A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. Three new analogues of UM171 were synthesized accordingly in excellent yields using the common indole-carboxamide intermediate. |
| doi_str_mv | 10.1021/acs.joc.6b01094 |
| format | Article |
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A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. Three new analogues of UM171 were synthesized accordingly in excellent yields using the common indole-carboxamide intermediate.</description><identifier>ISSN: 0022-3263</identifier><identifier>EISSN: 1520-6904</identifier><identifier>DOI: 10.1021/acs.joc.6b01094</identifier><identifier>PMID: 27337543</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Cell Self Renewal - drug effects ; Cyclization ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - drug effects ; Humans ; Indoles - chemical synthesis ; Indoles - pharmacology ; Pyrimidines - chemical synthesis ; Pyrimidines - pharmacology ; Spectrum Analysis</subject><ispartof>Journal of organic chemistry, 2016-11, Vol.81 (21), p.10236-10241</ispartof><rights>Copyright © 2016 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a333t-d33b8d9ac044792580b949cff456c8fb1ec223c0e4c39181bdd9ef33d10ab8273</citedby><cites>FETCH-LOGICAL-a333t-d33b8d9ac044792580b949cff456c8fb1ec223c0e4c39181bdd9ef33d10ab8273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.joc.6b01094$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.joc.6b01094$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27337543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ali, Sajjad</creatorcontrib><creatorcontrib>Yu, Shun-Ming</creatorcontrib><creatorcontrib>Yao, Zhu-Jun</creatorcontrib><title>Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal</title><title>Journal of organic chemistry</title><addtitle>J. Org. Chem</addtitle><description>A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. Three new analogues of UM171 were synthesized accordingly in excellent yields using the common indole-carboxamide intermediate.</description><subject>Cell Self Renewal - drug effects</subject><subject>Cyclization</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Humans</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - pharmacology</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Pyrimidines - pharmacology</subject><subject>Spectrum Analysis</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kDtPwzAURi0EoqUwsyGPSJDWr7xGVEGLVAQidI4c54amSuJiO0L997hKYcPLHXy-T_cehK4pmVLC6EwqO91qNY0KQkkqTtCYhowEUUrEKRoTwljAWcRH6MLaLfEvDMNzNGIx53Eo-BhtFka2QaZkA3glC22k02aPs33nNmBri3WF1y80pvdY4jftoHP44VN3tXWHr2Xfyg4vofWxna7B1QpnDlo8h6bBGTRV8A4dfMvmEp1VsrFwdZwTtH56_Jgvg9Xr4nn-sAok59wFJedFUqZSESHilIUJKVKRqqoSYaSSqqCgGOOKgFA8pQktyjKFivOSElkk_q4Juh16d0Z_9WBd3tZW-W1kB7q3OU1YFBPhZXl0NqDKaGsNVPnO1K00-5yS_KA393pzrzc_6vWJm2N5X7RQ_vG_Pj1wNwBDsjedv_Xfuh-R_YSZ</recordid><startdate>20161104</startdate><enddate>20161104</enddate><creator>Ali, Sajjad</creator><creator>Yu, Shun-Ming</creator><creator>Yao, Zhu-Jun</creator><general>American Chemical Society</general><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>7X8</scope></search><sort><creationdate>20161104</creationdate><title>Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal</title><author>Ali, Sajjad ; Yu, Shun-Ming ; Yao, Zhu-Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a333t-d33b8d9ac044792580b949cff456c8fb1ec223c0e4c39181bdd9ef33d10ab8273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cell Self Renewal - drug effects</topic><topic>Cyclization</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Humans</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - pharmacology</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Pyrimidines - pharmacology</topic><topic>Spectrum Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ali, Sajjad</creatorcontrib><creatorcontrib>Yu, Shun-Ming</creatorcontrib><creatorcontrib>Yao, Zhu-Jun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ali, Sajjad</au><au>Yu, Shun-Ming</au><au>Yao, Zhu-Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2016-11-04</date><risdate>2016</risdate><volume>81</volume><issue>21</issue><spage>10236</spage><epage>10241</epage><pages>10236-10241</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><abstract>A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. 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| language | eng |
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| source | MEDLINE; American Chemical Society Publications |
| subjects | Cell Self Renewal - drug effects Cyclization Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - drug effects Humans Indoles - chemical synthesis Indoles - pharmacology Pyrimidines - chemical synthesis Pyrimidines - pharmacology Spectrum Analysis |
| title | Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal |
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