85027-68-5Relevant academic research and scientific papers
Syntheses and biological evaluations of highly functionalized hydroxamate containing and N-methylthio monobactams as anti-tuberculosis and β-lactamase inhibitory agents
Majewski, Mark W.,Watson, Kyle D.,Cho, Sanghyun,Miller, Patricia A.,Franzblau, Scott G.,Miller, Marvin J.
supporting information, p. 141 - 147 (2016/01/30)
Both the resurgence of tuberculosis (TB) and antibiotic resistance continue to threaten modern healthcare and new means of combating pathogenic bacterial infections are needed. The syntheses of monobactams possessing hydroxamate and N-methylthio functionality are described, as well as their anti-TB, in vitro β-lactamase inhibitory, and general antimicrobial evaluations. A number of compounds exhibited significant anti-TB and β-lactamase inhibitory activity, with MIC values in the range of 25 to i values in the range of 25-0.03 μM against purified NDM-1 and VIM-1 lystate metallo β-lactamases. This work suggests that these scaffolds may serve as promising leads in developing new antibiotics and/or β-lactamase inhibitors.
Studies on the design and synthesis of new monocyclic β-lactams containing substructures of penicillin G
Lee, Sang Hyup
, p. 2990 - 2994 (2014/12/10)
The studies on design and synthesis of new monocyclic β-lactam esters 4(R/S)-(1′-methoxycarbonylpropyl-2′(R/S)-thio)-3(R)-phenylacetamidoazetidin-2-one (3a) and 4(R/S)-(1′-methoxycarbonyl-2′-methyl-propyl-2′-thio)-3(R)-phenylacetamidoazetidin-2-one (3b) were described. Compounds 3a and 3b were specifically designed to retain all penicillin substructures except the bicyclic system, which would be conceived by cleaving the C(3)-N(4) bond of penicillin G. Compounds 3a and 3b are of particular interest in the context of the structural elucidation of monocyclic β-lactams originated from penicillin. Key intermediates, β-mercapto esters 6a and 6b, were synthesized from conjugate acids 4a and 4b using three-step synthetic sequences, respectively, and 4(S)-acetoxy-3(S)-phenylacetamidoazetidin-2-one (7) was obtained from the degradation of penicillin G. Reactions of 6a and 6b with 7, thus obtained, provided the target compounds 3a and 3b, respectively.
Design and synthesis of new 4-alkylthio monocyclic β-lactams
Lee, Sang Hyup
, p. 121 - 127 (2013/08/24)
New types of monocyclic β-lactams constitute an important class of compounds due to their unique structures and natures. Here, the design and synthesis of new 4-alkylthio monocyclic β-lactams 2a and 3a are reported. Significantly, compounds 2a and 3a, while keeping a monocyclic system, were designed to contain all of the substructures provided by the cleavage of C(2)-C(3) bond in penicillins. Efficient synthetic pathways for compounds 2a and 3a were established based on two different strategies. Compound 2a was synthesized from raw materials, using 4-acetoxyazetidin-2-one as a key intermediate, through a ten-step synthetic sequence in 3% overall yield. Compound 3a was synthesized from potassium salt of penicillin G (17), using the degraded product 20 as a key intermediate, through a six-step synthetic sequence in 11% overall yield. 4-Alkylthioazetidin- 2-one derivatives, introduced in this study, could serve as valuable intermediates for the development of new monocyclic β-lactams.
A total synthesis of (1R,5R)-3-phenylmethyl-4-thia-2,6-diazabicyclo [3.2.0]hept-2-en-7-one, a useful intermediate for the preparation of penem and cepham derivatives
Cainelli, Gianfranco,Giacomini, Daria,Galletti, Paola
, p. 289 - 294 (2007/10/03)
The preparation of the thiazoline (1R,5R)-3-phenylmethyl-4-thia-2,6- diazabicyclo [3.2.0]hept-2-en-7-one (1) is presented. This compound, which has been extensively used as an intermediate for the synthesis of penems and cephams, has been obtained starting from a C-4 unsubstituted azetidinone by means of facile processes while chirality has been obtained through enzymatic resolution.
