Compound 1, a potent and irreversible inhibitor of β-lactamases, is in clinical trials with β-lactam antibiotics for the treatment of serious and antibiotic-resistant bacterial infections. A short, scalable, and cost-effective route for the production of this densely functionalized polycyclic molecule is described.
The solubility of two calcium channel blockers, felodipine and nitrendipine, was measured in liquid and supercritical carbon dioxide at (298, 308, and 318) K and at pressures between (80 and 250) bar. The solubilites were measured experimentally through two methods: cloud point measurements and UV absorption. At lower pressures, and hence densities, the UV method was more accurate while at higher pressures and densities the solubilities measured by both methods were basically identical. Both of these compounds showed an increase in solubility with increasing temperature and density. The experimentally determined solubility was accurately modeled using an equation, derived from association laws, which had a strong solvent density and temperature dependence.
A highly efficient TMSI-mediated deprotection and direct isolation method to obtain zwitterionic compounds from the corresponding N-Boc derivatives has been developed. This method has been demonstrated in the final deprotection/isolation of the β-lactamase inhibitor MK-7655 as a part of its manufacturing process. Further application of this process toward other zwitterionic compounds, such as dipeptides and tripeptides, has been successfully developed. Furthermore, a catalytic version of this transformation has been demonstrated in the presence of BSA or BSTFA.
An efficient iodotrimethylsilane-mediated deprotection and direct isolation method to obtain zwitterionic compounds from the corresponding N-Boc derivatives is developed. This method is successfully applied to model peptides as well as to the final deprotection/isolation of the -lactamase inhibitor MK-7655 (IV) as a part of its manufacturing process. -(LIU*, Z.; YASUDA, N.; SIMEONE, M.; REAMER, R. A.; J. Org. Chem. 79 (2014) 23, 11792-11796, http://dx.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.