1,721,117 research outputs found
A novel approach to a precursor of the carbapenem antibiotic PS-5 via aziridine stereospecific carbonylation
No full textCobalt carbonyl-catalyzed carbonylative ring expansion of optically-pure cis-1-benzyl-3-ethyl-2-hydroxymethylaziridine (5) to trans beta-lactam (8) afforded a key precursor of the carbapenem antibiotic (+)-PS-5. Aziridine (5) was obtained in both enantiomerically-pure forms by Amano PS lipase-catalyzed esterification in n.hexane using vinyl acetate as acyl donor. The stereochemical pathway of the carbonylation reaction was proved by configurational assignments through chemical correlation
Boronic acid inhibitors of beta-lactamases as therapeutic agents in treatment of antibiotic-resistant infection diseases
No full texthe invention relates to novel boronic acid compounds, a method for the preparation of such compounds, intermediate compounds for the preparation of such compounds, intermediate compounds for the use in a method for preparation of such compounds, a pharmaceutical composition, the use of one or more compounds discussed above or of a pharmaceutical composition in the manufacture of a medicament for the treatment of a bacterial infection, and a screening method
Applications of the (PhO)(3)PCl2 reagent: A new protocol for mild cleavage of sulfinamides and sulfonamides
No full textThe triphenyl phosphite-chlorine reagent, freshly in situ prepared by the action of chlorine on a solution of triphenyl phosphite in dichloromethane, is successfully used in the cleavage of both sulfonamides and sulfonamides under extremely mild conditions (-15 degrees C to r.t.). Final amines are easily recovered by a simple acid/base extraction, and no further purification is required
Stereoselective homologation of boronates in the total synthesis of the actin-targeting metabolite (-)-microcarpalide
No full textNanomolar beta-lactamase inhibitors
No full textNew .alpha.-boronated N-alkylamides, R1C(O)NHCHR2B(OH)2 (R1 = H, organyl, excluding R1 = Me, Ph; R2 = heterocyclyl, cycloalkenyl, alkenyl, alkyl), preferably N-acyl-3-aminomethylbenzoates (.alpha.R)-RC(O)NHCH[B(OH)2]-1,3-C6H4X [15-17; X = CO2H, R = Me, 2-thienylmethyl, 3-(2-chlorophenyl)-5-methylisoxazol-4-yl; 21, X = H, R = 2-thienylmethyl], designed as transition-state analog inhibitors effective against class C .beta.-lactamase AmpC, were prepd. by one-pot procedure comprising stereoselective dichlorocarbene insertion into B-C-bond of (+)-pinanediol 3-(4,4-dimethyl-2-oxazolinyl)phenylboronate (7), amination of the resulting QO2BCHCl-1,3-C6H4R3 [8; Q = (+)-pinanediyl, R3 = 4,4-dimethyl-2-oxazolinyl] and subsequent acylation. The new compds. improve inhibition by over two-orders of magnitude compared to analogous glycylboronic acids, with Ki values as low as 1 nM. In an example, (+)-pinanediol (1R)-1-(2-thienylacetylamino)-1-[3-(4,4-dimethyl-4,5-dihydro-2-oxazolyl)phenyl]methylboronate (11) was prepd. from 7 by reaction with LiCHCl2 at -80, followed by amination by LiN(TMS)2, desilylation, and acylation by Ac2O with 24% overall yield. In another example, compd. 10 was deprotected to give 3-[(R)-(borono)(2-thienylacetylamino)methyl]benzoic acid (16). Compd. 16 exhibited binding const. with AmpC .beta.-lactamase of 0.001 .mu.M, and synergic inhibiting effect on E.coli growth at min. inhibition concn. (MIC) of 1.mu.g/mL in combination with antibiotic ceftazidime; in the absence of 16 the MIC of ceftazidime was 32 .mu.g/mL
Alkene Metathesis in Organic Synthesis
No full textA review which is meant to give a broad overview of alkene metathesis reactions in org. synthesis, focusing in particular on the well-established ring closing metathesis and the emerging cross-metathesis methodologies, and on their application to natural product synthesis. Metathesis reactions involving alkynes as partners will also be discussed
Synthesis of [(1,2,3-Triazol-1-yl)methyl]boronic Acids Through Click Chemistry: Easy Access to a Potential Scaffold for Protease Inhibitors
No full textStereoselective synthesis of previously unreported [(1,2,3-triazol-1-yl)methyl]boronic acids has been achieved from azidomethylboronates by copper-catalyzed azide–alkyne cycloaddition reaction. The proximity of the cycloaddition reaction center to the boronic group is not detrimental to the stability of the sp3 C–B bond or to the stereoisomeric composition, which further expands the field of application of click chemistry to new boronate substrates and offers a new potential scaffold for protease inhibitors
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