- Chemical and Genetic Studies on the Formation of Pyrrolones During the Biosynthesis of Cytochalasans
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A key step during the biosynthesis of cytochalasans is a proposed Knoevenagel condensation to form the pyrrolone core, enabling the subsequent 4+2 cycloaddition reaction that results in the characteristic octahydroisoindolone motif of all cytochalasans. In this work, we investigate the role of the highly conserved α,β-hydrolase enzymes PyiE and ORFZ during the biosynthesis of pyrichalasin H and the ACE1 metabolite, respectively, using gene knockout and complementation techniques. Using synthetic aldehyde models we demonstrate that the Knoevenagel condensation proceeds spontaneously but results in the 1,3-dihydro-2H-pyrrol-2-one tautomer, rather than the required 1,5-dihydro-2H-pyrrol-2-one tautomer. Taken together our results suggest that the α,β-hydrolase enzymes are essential for first ring cyclisation, but the precise nature of the intermediates remains to be determined.
- Zhang, Haili,Hantke, Verena,Bruhnke, Pia,Skellam, Elizabeth J.,Cox, Russell J.
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supporting information
p. 3106 - 3113
(2021/01/20)
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- 6-FLUORO-7-(1-PIPERAZINYL)QUINOXALINE 1,4-DIOXIDES. PART I. 2-(N-2-HYDROXYALKYLCARBAMOYL) DERIVATIVES
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A series of N--β-aminoalkanol 1,4-dioxides (12a-h) have been synthesized for bioassay via the Beirut reaction of 5(6)-fluoro-6(5)-(4-methyl-1-piperazinyl)benzofuroxan (9) with the appropriate N-acetoacetyl-β-aminoalkanol in the presence of triethylamine.Preliminary in vitro investigations have indicated that none of the title compounds exhibits any significant antibacterial potency at concentrations /= 200 μg/ml.
- El-Abadelah, Mustafa M.,Nazer, Musa Z.,El-Abadla, Naser S.,Meier, Herbert
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p. 2203 - 2220
(2007/10/03)
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