Regio- and Stereoselective Synthesis of C‑4′ Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues
Novel C-4′,C-5′ cyclobutane-fused spirocyclic ribonucleoside analogues were prepared. Thermal [2 + 2] cycloaddition between dichloroketene and readily derived 4′-exo-methylene furanoses afforded a first entry to the required constrained ribofuranoses, relying on a carbonyl transposition sequence. Al...
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| Veröffentlicht in: | Organic letters 2021-11, Vol.23 (22), p.8828-8833 |
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| container_issue | 22 |
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| container_title | Organic letters |
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| creator | Jouffroy, Lucile Verhoeven, Jonas Brambilla, Marta Verniest, Guido Kong, Hanchu Zhao, Yongbin Wang, Wenbin Meerpoel, Lieven Thuring, Jan Willem Winne, Johan M |
| description | Novel C-4′,C-5′ cyclobutane-fused spirocyclic ribonucleoside analogues were prepared. Thermal [2 + 2] cycloaddition between dichloroketene and readily derived 4′-exo-methylene furanoses afforded a first entry to the required constrained ribofuranoses, relying on a carbonyl transposition sequence. Alternatively, an unusual stereoselective ionic [2 + 2] cycloaddition using methyl propiolate promoted by methylaluminoxane gave a complementary, more direct approach to such ribofuranoses. Further conversion to the constrained adenosine analogues revealed promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range. |
| doi_str_mv | 10.1021/acs.orglett.1c03334 |
| format | Article |
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Further conversion to the constrained adenosine analogues revealed promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range.</description><subject>Cycloaddition Reaction</subject><subject>Molecular Structure</subject><subject>Nucleosides - chemical synthesis</subject><subject>Nucleosides - chemistry</subject><subject>Protein-Arginine N-Methyltransferases - antagonists & inhibitors</subject><subject>Spiro Compounds - chemical synthesis</subject><subject>Spiro Compounds - chemistry</subject><subject>Stereoisomerism</subject><issn>1523-7060</issn><issn>1523-7052</issn><issn>1523-7052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UUtOwzAQtRCI_wmQkJdsUvxLTJal4ichkCisI8cZFyM3LnaClF2vwFU4EifB0MKS1Yxm3kd6D6EjSkaUMHqqdBz5MHPQdSOqCedcbKBdmjOeSZKzzb-9IDtoL8YXQmi6lNtohwvJCS_yXfT-ADPrM6zaBk87COAjONCdfQM8HdruGaKN2Bs8-Vy-i8_lB54ubPB60M7XfTc4_GBrb_qg2sTEU62M8a6JP4KPz2ADfkp3FfG59c7PrFbODXi8crjrtUuOtgE8blV69xAP0JZRLsLheu6jp8uLx8l1dnt_dTMZ32aKi7zLODOaFqIsiQIBpgbZSHZWk9yUteaSciY55DVhmilOVWmMyiVlUggli0Jovo9OVrqL4F-Tb1fNbdTgnGrB97FieckJk2elSFC-gurgYwxgqkWwcxWGipLqu4sqdVGtu6jWXSTW8dqgr-fQ_HF-w0-A0xXgm_3i-5AiiP9KfgEtv5x_</recordid><startdate>20211119</startdate><enddate>20211119</enddate><creator>Jouffroy, Lucile</creator><creator>Verhoeven, Jonas</creator><creator>Brambilla, Marta</creator><creator>Verniest, Guido</creator><creator>Kong, Hanchu</creator><creator>Zhao, Yongbin</creator><creator>Wang, Wenbin</creator><creator>Meerpoel, Lieven</creator><creator>Thuring, Jan Willem</creator><creator>Winne, Johan M</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><orcidid>https://orcid.org/0000-0003-4154-1586</orcidid><orcidid>https://orcid.org/0000-0002-9015-4497</orcidid><orcidid>https://orcid.org/0000-0002-4185-9458</orcidid></search><sort><creationdate>20211119</creationdate><title>Regio- and Stereoselective Synthesis of C‑4′ Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues</title><author>Jouffroy, Lucile ; Verhoeven, Jonas ; Brambilla, Marta ; Verniest, Guido ; Kong, Hanchu ; Zhao, Yongbin ; Wang, Wenbin ; Meerpoel, Lieven ; Thuring, Jan Willem ; Winne, Johan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a345t-32fc164990ae4efbe7d728b05f9bc3713273e5b02c2a31a9ffa5712744a7664c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cycloaddition Reaction</topic><topic>Molecular Structure</topic><topic>Nucleosides - chemical synthesis</topic><topic>Nucleosides - chemistry</topic><topic>Protein-Arginine N-Methyltransferases - antagonists & inhibitors</topic><topic>Spiro Compounds - chemical synthesis</topic><topic>Spiro Compounds - chemistry</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jouffroy, Lucile</creatorcontrib><creatorcontrib>Verhoeven, Jonas</creatorcontrib><creatorcontrib>Brambilla, Marta</creatorcontrib><creatorcontrib>Verniest, Guido</creatorcontrib><creatorcontrib>Kong, Hanchu</creatorcontrib><creatorcontrib>Zhao, Yongbin</creatorcontrib><creatorcontrib>Wang, Wenbin</creatorcontrib><creatorcontrib>Meerpoel, Lieven</creatorcontrib><creatorcontrib>Thuring, Jan Willem</creatorcontrib><creatorcontrib>Winne, Johan M</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>Organic letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jouffroy, Lucile</au><au>Verhoeven, Jonas</au><au>Brambilla, Marta</au><au>Verniest, Guido</au><au>Kong, Hanchu</au><au>Zhao, Yongbin</au><au>Wang, Wenbin</au><au>Meerpoel, Lieven</au><au>Thuring, Jan Willem</au><au>Winne, Johan M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regio- and Stereoselective Synthesis of C‑4′ Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues</atitle><jtitle>Organic letters</jtitle><addtitle>Org. 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| source | MEDLINE; American Chemical Society Journals |
| subjects | Cycloaddition Reaction Molecular Structure Nucleosides - chemical synthesis Nucleosides - chemistry Protein-Arginine N-Methyltransferases - antagonists & inhibitors Spiro Compounds - chemical synthesis Spiro Compounds - chemistry Stereoisomerism |
| title | Regio- and Stereoselective Synthesis of C‑4′ Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues |
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