Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid
The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protecte...
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| Veröffentlicht in: | Journal of medicinal chemistry 1985-12, Vol.28 (12), p.1903-1906 |
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| container_end_page | 1906 |
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| container_issue | 12 |
| container_start_page | 1903 |
| container_title | Journal of medicinal chemistry |
| container_volume | 28 |
| creator | Kukolja, Stjepan Pfeil, Janice L Draheim, Susan E Ott, John L |
| description | The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained. The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers. After removal of the protective groups, the S epimer was isolated. The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported. |
| doi_str_mv | 10.1021/jm00150a024 |
| format | Article |
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Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Kukolja, Stjepan ; Pfeil, Janice L ; Draheim, Susan E ; Ott, John L</creator><creatorcontrib>Kukolja, Stjepan ; Pfeil, Janice L ; Draheim, Susan E ; Ott, John L</creatorcontrib><description>The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained. The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers. After removal of the protective groups, the S epimer was isolated. The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00150a024</identifier><identifier>PMID: 2933520</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Administration, Oral ; Cephalosporins - chemical synthesis ; Cephalosporins - isolation & purification ; Cephalosporins - pharmacology ; Chemical Phenomena ; Chemistry ; Glycine - analogs & derivatives ; Gram-Positive Bacteria - drug effects ; Haemophilus influenzae - drug effects ; Staphylococcus - drug effects ; Stereoisomerism ; Streptococcus pneumoniae - drug effects ; Streptococcus pyogenes - drug effects ; Structure-Activity Relationship ; Thiophenes</subject><ispartof>Journal of medicinal chemistry, 1985-12, Vol.28 (12), p.1903-1906</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a354t-d1d4cb48e343a1afaddd49012609a796c5644cea7fe85056afca345189892ba13</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/jm00150a024$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00150a024$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2933520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kukolja, Stjepan</creatorcontrib><creatorcontrib>Pfeil, Janice L</creatorcontrib><creatorcontrib>Draheim, Susan E</creatorcontrib><creatorcontrib>Ott, John L</creatorcontrib><title>Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained. The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers. After removal of the protective groups, the S epimer was isolated. The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported.</description><subject>Administration, Oral</subject><subject>Cephalosporins - chemical synthesis</subject><subject>Cephalosporins - isolation & purification</subject><subject>Cephalosporins - pharmacology</subject><subject>Chemical Phenomena</subject><subject>Chemistry</subject><subject>Glycine - analogs & derivatives</subject><subject>Gram-Positive Bacteria - drug effects</subject><subject>Haemophilus influenzae - drug effects</subject><subject>Staphylococcus - drug effects</subject><subject>Stereoisomerism</subject><subject>Streptococcus pneumoniae - drug effects</subject><subject>Streptococcus pyogenes - drug effects</subject><subject>Structure-Activity Relationship</subject><subject>Thiophenes</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkUtrFEEUhQtR4hhduRZ65QOpsV79WkpwEiGQIUZ0V9yuvp3UWN3VqaqRtP_Ef2uHHkIWru7i-zgHziXkNWdrzgT_tOsZ4zkDJtQTsuK5YFRVTD0lK8aEoKIQ8jl5EeOOMSa5kEfkSNRSzt6K_L0I4NyUQRN9aKBxmBkcb8D5OPpghwyGZBvrkzVxncl1tg04QoBk_ZD5LpuR89fWLCEm2d-YXVIbfY_hnpf0vaQNDn98urE4TO7aTWZy0NvWf2gRDCZ_Nz2qhMGaOci2L8mzDlzEV4d7TL5vvlydnNHzi9OvJ5_PKchcJdryVplGVSiVBA4dtG2rasZFwWoo68LkhVIGoeywylleQGdAqpxXdVWLBrg8Jm-X3DH42z3GpHsbDToHA_p91GWhal4XchY_LqIJPsaAnR6D7SFMmjN9_wj96BGz_eYQu296bB_cw_Izpwu3MeHdA4bwSxelLHN9tf2mf2w3l6flzzO9mf13iw8m6p3fh2Ee5b_N_wDzt6Jy</recordid><startdate>198512</startdate><enddate>198512</enddate><creator>Kukolja, Stjepan</creator><creator>Pfeil, Janice L</creator><creator>Draheim, Susan E</creator><creator>Ott, John L</creator><general>American Chemical Society</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>198512</creationdate><title>Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid</title><author>Kukolja, Stjepan ; Pfeil, Janice L ; Draheim, Susan E ; Ott, John L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a354t-d1d4cb48e343a1afaddd49012609a796c5644cea7fe85056afca345189892ba13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Administration, Oral</topic><topic>Cephalosporins - chemical synthesis</topic><topic>Cephalosporins - isolation & purification</topic><topic>Cephalosporins - pharmacology</topic><topic>Chemical Phenomena</topic><topic>Chemistry</topic><topic>Glycine - analogs & derivatives</topic><topic>Gram-Positive Bacteria - drug effects</topic><topic>Haemophilus influenzae - drug effects</topic><topic>Staphylococcus - drug effects</topic><topic>Stereoisomerism</topic><topic>Streptococcus pneumoniae - drug effects</topic><topic>Streptococcus pyogenes - drug effects</topic><topic>Structure-Activity Relationship</topic><topic>Thiophenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kukolja, Stjepan</creatorcontrib><creatorcontrib>Pfeil, Janice L</creatorcontrib><creatorcontrib>Draheim, Susan E</creatorcontrib><creatorcontrib>Ott, John L</creatorcontrib><collection>Istex</collection><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 medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kukolja, Stjepan</au><au>Pfeil, Janice L</au><au>Draheim, Susan E</au><au>Ott, John L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>1985-12</date><risdate>1985</risdate><volume>28</volume><issue>12</issue><spage>1903</spage><epage>1906</epage><pages>1903-1906</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts. The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5). The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7. After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained. The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers. After removal of the protective groups, the S epimer was isolated. The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>2933520</pmid><doi>10.1021/jm00150a024</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 1985-12, Vol.28 (12), p.1903-1906 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_76491963 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Administration, Oral Cephalosporins - chemical synthesis Cephalosporins - isolation & purification Cephalosporins - pharmacology Chemical Phenomena Chemistry Glycine - analogs & derivatives Gram-Positive Bacteria - drug effects Haemophilus influenzae - drug effects Staphylococcus - drug effects Stereoisomerism Streptococcus pneumoniae - drug effects Streptococcus pyogenes - drug effects Structure-Activity Relationship Thiophenes |
| title | Orally absorbable cephalosporin antibiotics. 3. Preparation of biologically active R-isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid |
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