Chemistry of cephalosporin antibiotics. XIX. Transformation of .DELTA.2-cephem to .DELTA.3-cephem by oxidation-reduction at sulfur

Kaiser, Gary V.; Cooper, R. D. G.; Koehler, R. E.; Murphy, C. F.; Webber, J. A.; Wright, I. G.; Heyningen, E. M. Van

doi:10.1021/jo00832a081

Cited by 74 publications

(10 citation statements)

References 3 publications

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“…To circumvent the Δ 2 –Δ 3 isomerization issue, oxidation of the thiazine sulfur atom with m CPBA was performed prior to alkylation (Scheme 1A). 29 The Δ 3 -alkene ( S )-sulfoxide 2 was obtained in good yield (72%); subsequent alkylation with MMC in the presence of N , N ′-diisopropylethylamine gave 3 as a single isolate isomer in reasonable yield (49%). Acid-mediated PMB deprotection yielded FC2 in good yield (88%).…”

Section: Resultsmentioning

confidence: 98%

Assay Platform for Clinically Relevant Metallo-β-lactamases

et al. 2013

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Metallo-β-lactamases (MBLs) are a growing threat to the use of almost all clinically used β-lactam antibiotics. The identification of broad-spectrum MBL inhibitors is hampered by the lack of a suitable screening platform, consisting of appropriate substrates and a set of clinically relevant MBLs. We report procedures for the preparation of a set of clinically relevant metallo-β-lactamases (i.e., NDM-1 (New Delhi MBL), IMP-1 (Imipenemase), SPM-1 (São Paulo MBL), and VIM-2 (Verona integron-encoded MBL)) and the identification of suitable fluorogenic substrates (umbelliferone-derived cephalosporins). The fluorogenic substrates were compared to chromogenic substrates (CENTA, nitrocefin, and imipenem), showing improved sensitivity and kinetic parameters. The efficiency of the fluorogenic substrates was exemplified by inhibitor screening, identifying 4-chloroisoquinolinols as potential pan MBL inhibitors.

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Section: Resultsmentioning

confidence: 98%

Assay Platform for Clinically Relevant Metallo-β-lactamases

et al. 2013

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“…This oxidation converts the C-3 double bond isomer into the C-2 double bond isomer. This process is based on the fact that β,γ-unsaturated sulfoxides are thermodynamically more stable than the corresponding α,β-unsaturated ones [ 19 ]. This oxidation process gave rise to a new cephalothin derivative 5 , which can be used to attach a variety of compounds containing an amino group.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Total 1H- and 13C-NMR Assignment of Cephem Derivatives for Use in ADEPT Approaches

et al. 2008

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We report the synthesis and total NMR characterization of 5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylic acid-3-[[[(4’’-nitrophenoxy)carbonyl]oxy]-methyl]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (5), a new cephalosporin derivative. This compound can be used as the carrier of a wide range of drugs containing an amino group. The preparation of the intermediate product, 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]-diphenylmethyl ester-5-dioxide (6), as well as the synthesis of the antimalarial primaquine prodrug 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-3-[methyl 4-(6-methoxyquinolin-8-ylamino)pentylcarbamate]-8-oxo-7-[(2-thienyloxoacetyl)amino]- 5-dioxide (7) are also described, together with their total 1H- and 13C-NMR assignments.

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“…The sulfoxide function has a stabilizing effect on this molecule as has been demonstrated before 24. Finally, reduction of sulfoxide 15 to sulfide 14 could be accomplished by treatment with acetyl chloride in DMF and a catalytic amount of tin(II) chloride analogous to Kaiser et al25 Thus, the above‐mentioned detour to target compound 14 via the sulfoxide route was indeed possible.…”

Section: Resultsmentioning

confidence: 99%