Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library
Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibi...
Gespeichert in:
| Veröffentlicht in: | Bioorganic & medicinal chemistry 2008-12, Vol.16 (24), p.10198-10204 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 10204 |
|---|---|
| container_issue | 24 |
| container_start_page | 10198 |
| container_title | Bioorganic & medicinal chemistry |
| container_volume | 16 |
| creator | Tsou, En-Lun Chen, Sih-Yu Yang, Ming-Hsun Wang, Shih-Chi Cheng, Ting-Ren Rachel Cheng, Wei-Chieh |
| description | Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly,
15 and
19 show better inhibitory activities than radicamine A (
20) and B (
18) against α-glucosidases. The IC
50 values of
15 and
19 are 1.1 and 0.5
μM, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases. |
| doi_str_mv | 10.1016/j.bmc.2008.10.063 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_883018922</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0968089608010249</els_id><sourcerecordid>883018922</sourcerecordid><originalsourceid>FETCH-LOGICAL-c479t-6be2e42816ed7a191a4aaf533bcdaf50e1be3a7e975bcec103220849bd68187f3</originalsourceid><addsrcrecordid>eNp9kMFu1DAQhi0EokvhAbigXFBPWTx2mtjihKqWIlXiQHu2xvaEevHGi52tyNvj1a7g1tPInu__NfoYew98DRz6T5u13bq14FzV95r38gVbQdd3rZQaXrIV171qudL9GXtTyoZzLjoNr9kZ6JoBgBVzP5ZpfqQSSoOTb2xIMf0MDmNDTxj3OIc0NWlssBEt5iU2uxSXx8Xn9GeJOJNvdkvOKQYfJmow_sKYgm8tlrqKweYaestejRgLvTvNc_Zwc31_ddveff_67erLXeu6Qc9tb0lQJxT05AcEDdghjpdSWufr5ASWJA6kh0vryAGXQnDVaet7BWoY5Tm7OPbucvq9pzKbbSiOYsSJ0r4YpSQHpYWoJBxJl1MpmUazy2FbTzXAzUGt2Ziq1hzUHr6q2pr5cGrf2y35_4mTywp8PAFYqsAx4-RC-ccJrjvOu0PR5yNH1cVToGyKCzQ58iGTm41P4Zkz_gIlN5gi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>883018922</pqid></control><display><type>article</type><title>Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Tsou, En-Lun ; Chen, Sih-Yu ; Yang, Ming-Hsun ; Wang, Shih-Chi ; Cheng, Ting-Ren Rachel ; Cheng, Wei-Chieh</creator><creatorcontrib>Tsou, En-Lun ; Chen, Sih-Yu ; Yang, Ming-Hsun ; Wang, Shih-Chi ; Cheng, Ting-Ren Rachel ; Cheng, Wei-Chieh</creatorcontrib><description>Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly,
15 and
19 show better inhibitory activities than radicamine A (
20) and B (
18) against α-glucosidases. The IC
50 values of
15 and
19 are 1.1 and 0.5
μM, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2008.10.063</identifier><identifier>PMID: 19008111</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Alkaloids - chemical synthesis ; Alkaloids - chemistry ; Alkaloids - pharmacology ; alpha-Glucosidases - metabolism ; beta-Mannosidase - antagonists & inhibitors ; beta-Mannosidase - metabolism ; Biological and medical sciences ; Chiral cyclic nitrone ; Drug Design ; General and cellular metabolism. Vitamins ; Glycosidase inhibitors ; Glycoside Hydrolase Inhibitors ; Inhibitory Concentration 50 ; Medical sciences ; Natural product-like molecule ; Pharmacology. Drug treatments ; Polyhydroxylated pyrrolidine alkaloid ; Pyrrolidines - chemical synthesis ; Pyrrolidines - chemistry ; Pyrrolidines - pharmacology ; Stereoisomerism ; Structural diversity</subject><ispartof>Bioorganic & medicinal chemistry, 2008-12, Vol.16 (24), p.10198-10204</ispartof><rights>2008 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-6be2e42816ed7a191a4aaf533bcdaf50e1be3a7e975bcec103220849bd68187f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2008.10.063$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20940043$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19008111$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsou, En-Lun</creatorcontrib><creatorcontrib>Chen, Sih-Yu</creatorcontrib><creatorcontrib>Yang, Ming-Hsun</creatorcontrib><creatorcontrib>Wang, Shih-Chi</creatorcontrib><creatorcontrib>Cheng, Ting-Ren Rachel</creatorcontrib><creatorcontrib>Cheng, Wei-Chieh</creatorcontrib><title>Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly,
15 and
19 show better inhibitory activities than radicamine A (
20) and B (
18) against α-glucosidases. The IC
50 values of
15 and
19 are 1.1 and 0.5
μM, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases.</description><subject>Alkaloids - chemical synthesis</subject><subject>Alkaloids - chemistry</subject><subject>Alkaloids - pharmacology</subject><subject>alpha-Glucosidases - metabolism</subject><subject>beta-Mannosidase - antagonists & inhibitors</subject><subject>beta-Mannosidase - metabolism</subject><subject>Biological and medical sciences</subject><subject>Chiral cyclic nitrone</subject><subject>Drug Design</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Glycosidase inhibitors</subject><subject>Glycoside Hydrolase Inhibitors</subject><subject>Inhibitory Concentration 50</subject><subject>Medical sciences</subject><subject>Natural product-like molecule</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyhydroxylated pyrrolidine alkaloid</subject><subject>Pyrrolidines - chemical synthesis</subject><subject>Pyrrolidines - chemistry</subject><subject>Pyrrolidines - pharmacology</subject><subject>Stereoisomerism</subject><subject>Structural diversity</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi0EokvhAbigXFBPWTx2mtjihKqWIlXiQHu2xvaEevHGi52tyNvj1a7g1tPInu__NfoYew98DRz6T5u13bq14FzV95r38gVbQdd3rZQaXrIV171qudL9GXtTyoZzLjoNr9kZ6JoBgBVzP5ZpfqQSSoOTb2xIMf0MDmNDTxj3OIc0NWlssBEt5iU2uxSXx8Xn9GeJOJNvdkvOKQYfJmow_sKYgm8tlrqKweYaestejRgLvTvNc_Zwc31_ddveff_67erLXeu6Qc9tb0lQJxT05AcEDdghjpdSWufr5ASWJA6kh0vryAGXQnDVaet7BWoY5Tm7OPbucvq9pzKbbSiOYsSJ0r4YpSQHpYWoJBxJl1MpmUazy2FbTzXAzUGt2Ziq1hzUHr6q2pr5cGrf2y35_4mTywp8PAFYqsAx4-RC-ccJrjvOu0PR5yNH1cVToGyKCzQ58iGTm41P4Zkz_gIlN5gi</recordid><startdate>20081215</startdate><enddate>20081215</enddate><creator>Tsou, En-Lun</creator><creator>Chen, Sih-Yu</creator><creator>Yang, Ming-Hsun</creator><creator>Wang, Shih-Chi</creator><creator>Cheng, Ting-Ren Rachel</creator><creator>Cheng, Wei-Chieh</creator><general>Elsevier Ltd</general><general>Elsevier</general><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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20081215</creationdate><title>Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library</title><author>Tsou, En-Lun ; Chen, Sih-Yu ; Yang, Ming-Hsun ; Wang, Shih-Chi ; Cheng, Ting-Ren Rachel ; Cheng, Wei-Chieh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-6be2e42816ed7a191a4aaf533bcdaf50e1be3a7e975bcec103220849bd68187f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Alkaloids - chemical synthesis</topic><topic>Alkaloids - chemistry</topic><topic>Alkaloids - pharmacology</topic><topic>alpha-Glucosidases - metabolism</topic><topic>beta-Mannosidase - antagonists & inhibitors</topic><topic>beta-Mannosidase - metabolism</topic><topic>Biological and medical sciences</topic><topic>Chiral cyclic nitrone</topic><topic>Drug Design</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Glycosidase inhibitors</topic><topic>Glycoside Hydrolase Inhibitors</topic><topic>Inhibitory Concentration 50</topic><topic>Medical sciences</topic><topic>Natural product-like molecule</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyhydroxylated pyrrolidine alkaloid</topic><topic>Pyrrolidines - chemical synthesis</topic><topic>Pyrrolidines - chemistry</topic><topic>Pyrrolidines - pharmacology</topic><topic>Stereoisomerism</topic><topic>Structural diversity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsou, En-Lun</creatorcontrib><creatorcontrib>Chen, Sih-Yu</creatorcontrib><creatorcontrib>Yang, Ming-Hsun</creatorcontrib><creatorcontrib>Wang, Shih-Chi</creatorcontrib><creatorcontrib>Cheng, Ting-Ren Rachel</creatorcontrib><creatorcontrib>Cheng, Wei-Chieh</creatorcontrib><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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsou, En-Lun</au><au>Chen, Sih-Yu</au><au>Yang, Ming-Hsun</au><au>Wang, Shih-Chi</au><au>Cheng, Ting-Ren Rachel</au><au>Cheng, Wei-Chieh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2008-12-15</date><risdate>2008</risdate><volume>16</volume><issue>24</issue><spage>10198</spage><epage>10204</epage><pages>10198-10204</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly,
15 and
19 show better inhibitory activities than radicamine A (
20) and B (
18) against α-glucosidases. The IC
50 values of
15 and
19 are 1.1 and 0.5
μM, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19008111</pmid><doi>10.1016/j.bmc.2008.10.063</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0968-0896 |
| ispartof | Bioorganic & medicinal chemistry, 2008-12, Vol.16 (24), p.10198-10204 |
| issn | 0968-0896 1464-3391 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_883018922 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Alkaloids - chemical synthesis Alkaloids - chemistry Alkaloids - pharmacology alpha-Glucosidases - metabolism beta-Mannosidase - antagonists & inhibitors beta-Mannosidase - metabolism Biological and medical sciences Chiral cyclic nitrone Drug Design General and cellular metabolism. Vitamins Glycosidase inhibitors Glycoside Hydrolase Inhibitors Inhibitory Concentration 50 Medical sciences Natural product-like molecule Pharmacology. Drug treatments Polyhydroxylated pyrrolidine alkaloid Pyrrolidines - chemical synthesis Pyrrolidines - chemistry Pyrrolidines - pharmacology Stereoisomerism Structural diversity |
| title | Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T05%3A10%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis%20and%20biological%20evaluation%20of%20a%202-aryl%20polyhydroxylated%20pyrrolidine%20alkaloid-based%20library&rft.jtitle=Bioorganic%20&%20medicinal%20chemistry&rft.au=Tsou,%20En-Lun&rft.date=2008-12-15&rft.volume=16&rft.issue=24&rft.spage=10198&rft.epage=10204&rft.pages=10198-10204&rft.issn=0968-0896&rft.eissn=1464-3391&rft_id=info:doi/10.1016/j.bmc.2008.10.063&rft_dat=%3Cproquest_cross%3E883018922%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=883018922&rft_id=info:pmid/19008111&rft_els_id=S0968089608010249&rfr_iscdi=true |