Forty years of peptide chemistry.
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Biomedical subjects
Publications and source records attributed to J C Sheehan.
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Antibiotic and penicillinase inhibitor activities of various penicillin and cephalosporin analogs are reported. The compounds include C-6 penicillin and C-7 cephalosporin carbon, oxygen and sulfur analogs obtained by replacing the NH of the amide side chains with CH2, O and S, respectively. In almost all cases, analogs were considerably less active than the standard compounds (benzylpenicillin and cephalothin). However, some of the analogs act as penicillinase inhibitors.
As part of a general program of structural modification in beta-lactam antibiotics, we have synthesized several simple penicillins from 6-aminopenicillanic acid where the C-3 carboxyl group has been replaced by a hydroxy or an acetoxy group and the C-6 side chain has been substituted by bromine or hydrogen. Some of the compounds exhibit mild activity against the Gram-positive strain Bacillus subtilis.
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Delta1-Tetrahydrocannabinol, which is resinous and insoluble in water and therefore difficult to study pharmacologically, can be converted to a watersoluble derivative without loss of its biological activity. This has been achieved by preparing esters bearing a nitrogen moiety with the use of carbodiimide as the condensing agent. The availability of such water-soluble derivatives will allow the evaluation of Delta1-tetrahydrocannabinol in self-administration studies in monkeys for its addiction liability potential in man. This technique of water solubilization is also applicable to other compounds of chemical and biological significance.
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