4-Alkylated monobactams
| Autor: | H. W. Chang, F. Massa, W. H. Koster, Richard B. Sykes, E. R. Weaver, David R. Kronenthal, William A. Slusarchyk, J. Pluscec, M. Taylor, Christopher M. Cimarusti, David M. Floyd, Richard H. Mueller, Thomas P. Kissick, Alan William Fritz, Hermann Breuer, D. P. Bonner |
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| Rok vydání: | 1983 |
| Předmět: |
chemistry.chemical_classification
biology Chemistry Organic Chemistry Enantioselective synthesis Grignard reaction Alkylation biology.organism_classification Biochemistry Medicinal chemistry chemistry.chemical_compound Drug Discovery Organic chemistry Monobactams Antibacterial activity Alkyl Bacteria |
| Zdroj: | Tetrahedron. 39:2577-2589 |
| ISSN: | 0040-4020 |
| Popis: | The synthesis of 4-alkylated monobactams by a variety of procedures is described. Two complementary procedures have been developed for the chiral synthesis of rnonobactams. (1) sulfonation of 4-alkyl-3-(protected)amino-2-azetidinones with vanous complexes of SO3, and (2) cyclization of β mesyloxyacyl sulfamates derived from β-alkyl-β-hydroxy-α-amino acids The most general procedure involves introduction of the alkyl group via a Grignard reaction on 6-APA-derived sulfones 23 or 24 followed by sulfonation. For the specific case of (3S,trans)-3-amino-4-methylmonobactamic acid (48). cyclization of the β-mesyloxyacyl sulfamate 40 derived from (L)-threonine is the preferred route. The introduction of 4-alkyl groups into monobactams results in a decrease in activity against gram-positive bacteria, an increase in activity against gram-negative bacteria, and an increase in β-lactamase stability. Increasing the size of the alkyl group beyond methyl results in diminished intrinsic antibacterial activity. 4β-Alkylmonobactams display better β-lactamase stability than their 4α-counterparts. |
| Databáze: | OpenAIRE |
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