Abstract
Alkylation of cefotaxime sodium with 1-iodoethyl 2-N(Boc)-D- phenylglycine (3a and 3b) led to double esters 4a, 4b where the carboxyl group of D-phenylglycine was linked to the 4-carboxyl group of cefotaxime via an ethyledine moiety, and their Δ2 isomeric analogues 5a and 5b. The Δ3→Δ2 isomeric transformation from 4a and 4b to 5a and 5b during the synthesis was successfully eliminated by the addition of TBA+HSO4- to the reaction media. Hydrolysis of the mixture of 4a and 4b followed by medium pressure liquid chromatographic separation afforded the D-phenylglycine- containing double ester prodrugs of cefotaxime (1a and 1b). Compounds 1a and 1b were stable in acidic phosphate buffer solution, but were degraded fairly rapidly in a pH 7.39 phosphate buffer solution. The t 1/4 of 1a and 1b in mucosal suspension prepared from rat intestine were 11 minutes and 1 minute respectively. These two compounds failed to demonstrate satisfactory stability for formulation as oral prodrugs of cefotaxime.
Original language | English |
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Pages (from-to) | 477-484 |
Number of pages | 8 |
Journal | Journal of Food and Drug Analysis |
Volume | 6 |
Issue number | 2 |
State | Published - 06 1998 |
Externally published | Yes |
Keywords
- Cefotaxime prodrugs
- D-phenylglycine
- Tetrabutylammonium hydrogen sulfate