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 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.
Kukolja
S
S
Pfeil
J L
JL
Draheim
S E
SE
Ott
J L
JL
D000284:Administration, Oral; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D005998:Glycine / Q000031:analogs & derivatives; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006193:Haemophilus influenzae / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes
D002511:Cephalosporins; D013876:Thiophenes; C048386:LY 164846; D005998:Glycine