20425-27-8Relevant academic research and scientific papers
Comparison of various density functional methods for distinguishing stereoisomers based on computed1H or13C NMR chemical shifts using diastereomeric penam β-lactams as a test set
Wiitala, Keith W.,Cramer, Christopher J.,Hoye, Thomas R.
, p. 819 - 829 (2007)
Full 1H and 13C NMR chemical shift assignments were made for two sets of penam β-lactams: namely, the diastereomeric (2S,5S,6S)-, (2S,5R,6R)-, (2S,5S,6R)-, and (2S, 5R, 6S)-methyl 6-(1,3-dioxoisoindolin-2-yl)3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0] heptane-2-carboxylates (1-4) and (2S,5R,6R)-, (2S,5S,6R)-, and (2S,5R,6S)-6-(1,3-dioxoisoindolin-2-yl)-3,3-dimethyl-7-oxo-4-thia-1-aza- bicyclo[3.2.0]heptane-2carboxylic acids (6-8). Each penam was then modeled as a family of conformera obtained from Monte Carlo searches using the AMBER* force field followed by IEFPCM/B3LYP/6-31G(d) geometry optimization of each conformer using chloroform solvation. 1H and 13C chemical shifts for each conformer were computed at the WF04, WC04, B3LYP, and PBE1 density functional levels as Boltzmann averages of IEFPCM/B3LYP/6-311+G(2d,p) energies over each family. Comparisons between experimental and theoretical chemical shift data were made using the total absolute error (|Δδ|T) criterion. For the 1H shift data, all methods were sufficiently accurate to identify the proper stereoisomers. Computed 13C shifts were not always successful in identifying the correct stereoisomer, regardless of which DFT method was used. The relative ability of each theoretical approach to discriminate among stereoisomers on the basis of proton shifts was also evaluated. Copyright
A thermal decarbonylation of penam β-lactams
Wiitala, Keith W.,Tian, Zhixin,Cramer, Christopher J.,Hoye, Thomas R.
, p. 3024 - 3031 (2008)
(Chemical Equation Presented) Penam acids 6-8 [i.e., (2S,5R,6R)-, (2S,5S,6R)-, and (2S,5R,6S)-isomers of 6-(1,3-dihydro-1,3-dioxo-2H-isoindol-2- yl)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid] were prepared by deesterification of the corresponding methyl esters 2-4. The same methodology applied to ester 1 did not lead to the (2S,5S,6S)-isomer 5 but rather a 72% yield of the thiazoline derivative 9. High-resolution mass spectrometry analysis of the reaction headspace gases indicated that a stoichiometric amount of carbon monoxide is produced during the deesterification of 1. A mechanism for this decarbonylation reaction is proposed. This appears to represent a new type of fragmentation reaction for a penam carboxylic acid. The free energies of various reaction species along viable decarbonylation reaction coordinates for acids 5 and 7 were computed by using the density functional theory method IEFPCM/M06/6-31+G(d). Anionic and zwitterionic (neutral) variants of the proposed mechanism were considered, but each produced computed activation free energies deemed to be too high (>45 kcal/mol) to be experimentally relevant. The computed activation free energies for the protonated (cationic) variant of the mechanism were 17.3 kcal/mol for 7 vs 8.8 kcal/mol for 5. The value of this difference in energies of activation (ΔΔG?) is quite consistent with experimental observations and supports the proposed mechanism. For a portion of the computed reaction coordinate that involves ring opening of the lactam ring by an internal carboxylic acid group to form a cyclic anhydride, the expected tetrahedral intermediate was circumvented by a direct (concerted) and facile N- to O-acyl migration event. Additional thermal gas-phase reaction products produced during gas chromatographic analysis of the penams 1-8 were characterized with high-resolution mass spectrometry, and possible mechanisms for their formation are presented.
PEPTIDE ANTIBIOTICS AND METHODS OF USE THEREOF
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Page/Page column 28, (2020/11/30)
The invention features peptide antibiotic compositions and methods of using such compositions for the treatment of bacterial infections (e.g., vancomycin resistant infections).
Asymmetric synthesis of new β-lactam lipopeptides as bacterial signal peptidase i inhibitors
Crauste, Celine,Froeyen, Matheus,Anne, Jozef,Herdewijn, Piet
experimental part, p. 3437 - 3449 (2011/09/12)
The transmembrane bacterial enzyme, signal peptidase I, is recognized as being a promising target for reducing the emergence of drug resistance. The asymmetric synthesis and the biological evaluation of original β-lactam lipopeptides have been performed t
Syntheses of (6S)-cephalosporins from 6-aminopenicillanic acid
Fekner, Tomasz,Baldwin, Jack E,Adlington, Robert M,Jones, Timothy W,Prout, C.Keith,Schofield, Christopher J
, p. 6053 - 6074 (2007/10/03)
Two practical routes to (6S,7S)-cephalosporins from 6-aminopenicillanic acid (6-APA) are described. In the first, 6-APA was converted to (2S,4S,5S,6S)-penicillin sulfoxide 49, which underwent Morin ring expansion to a protected (6S,7S)-cephem 50. In the s
Syntheses of (6S,7S)- and (6S,7R)-deacetoxycephalosporanic acids from 6-aminopenicillanic acid
Fekner, Tomasz,Baldwin, Jack E.,Adlington, Robert M.,Schofield, Christopher J.
, p. 1989 - 1990 (2007/10/03)
Two practical (i.e. applicable to multigram scale synthesis) approaches to (6S,7S)-cephalosporins (i.e. the enantiomers of naturally occuring cephalosporins) and the (6S)-epimers of cephalosporins from readily available (2S,5R,6R)-6-aminopenicillanic acid
Syntheses of (2S,3S)-[4,4,4-2H3]- and (2S,3R)-[4,4,4-2H3]Penicillamine
Nanjappan,Ramalingam,Mosberg,Woodard
, p. 421 - 425 (2007/10/02)
(2S,3S)-[4,4,4-2H3]- and (2S,3R)-[4,4,4-2H3]Penicillamine (2-amino-3-mercapto-3-methyl-[4,4,4-2H3]butanoic acids) were synthesized from benzyl (1S,3S,6R)-6-(phenoxyacetylamino)penicillanate
