[en] Highlights: • A unitary mechanism for the cyclization of tetraketides in stilbene and chalcone synthase. • The identification of an active water that functions as a “Claisen switch” in chalcone synthase. • QM-MM and FMO analysis of model tetraketide ligands highlighting common and disparate components of binding pockets and cyclization sites in stilbene and chalcone synthase. The polyketide synthases found in a variety of plants and fungi provide a varied source of biologically active compounds of pharmacological and medicinal interest. Stilbene synthase and chalcone synthase catalyze the formation of a common tetraketide intermediate, but use different cyclization mechanisms to produce distinct and separate natural products. While key structural differences have been identified to explain this functional diversity, a fuller explication of the factors responsible for this mechanistic disparity is required. Based on the energetics of our models of the bound tetraketides, and our structural analysis of the active sites we propose that a key tautomeric conversion provides a mechanistic framework common to both cyclizations. A previously unidentified active water molecule facilitates cyclization in chalcone synthase through a Claisen mechanism. Such a “Claisen switch” is comparable to the previously characterized “aldol switch” mechanism proposed for the biosynthesis of resveratrol in stilbene synthase.

[en] The sequential Michael addition/retro-Claisen condensation of 1,3-diarylpropan-1,3-diones with nitrostyrenes is described. 4-Nitro-1,3-diarylbutan-1-ones were efficiently synthesized in good to high yield under mild, transition-metal-free condition. This one-step method involving sequential carbon-carbon bond formation and cleavage provides a good alternative to the synthesis of various $\mathrm{\gamma <!--\; ??\; -->}$-nitro ketones.

Graphical abstract

The sequential Michael addition/retro-Claisen condensation of 1,3-diarylpropan-1,3-diones with nitrostyrenes is described. 4-Nitro-1,3-diarylbutan-1-ones were efficiently synthesized in good to high yield under mild and transition-metal-free condition. .

[en] The title compound, 3-(2,4-dichlorophenyl)-2-phenyl-5-(p-tolyl)- 7-(trifluoromethyl)pyrazolo[1,5-a] pyrimidine (C/sub 26/H/sub 16/Cl/sub 2/F/sub 3/N/sub 3/, Mr = 498.32) has been synthesized by condensation of 4,4,4-trifluoro-1-(p-tolyl)butane- 1,3-dione with 4-(2,4-dichlorophenyl)-3-phenyl-1H-pyrazol-5-amine. The latter was prepared from 2,4-dichlorophenylaceton itrile and ethyl benzoate through Claisen condensation and then cyclization with hydrazine hydrate. The crystal structure of the title compound was determined. In addition, the title compound possesses marked inhibition against the proliferation of human lung adenocarcinoma cell line A549 and human gastric cancer cell line MKN45, displaying promising anticancer activities. (author)

[en] A method was developed for the preparation of [U-¹⁴C]6-methyluracil by condensation of the sodium salt of [1,2,3,4-¹⁴C] ethyl acetoacetate with thio [¹⁴C]urea in anhydrous ethanol. The reaction yield was 21% (related to the activity of consumed components). The starting [1,2,3,4-¹⁴C] ethyl acetoacetate was prepared by the Claisen condensation of [1,2-¹⁴C] ethyl acetate in the presence of triphenyl methylsodium in anhydrous ether. Radiochemical purity verified by paper chromatography in three solvent systems was found to be better than 98%. Molar activity of [U-¹⁴C]6-methyluracil was greater than 200 mCi/mM. (author)

[en] The cyclization-induced rearrangement mechanism proposed by Overman to account for nucleophilic catalysis of the thio-Claisen rearrangement has been tested by application of two criteria, viz., the secondary kinetic deuterium isotope effect at the β (side chain) carbon in phenyl allyl sulfide and the substituent rate effect. The results (k/sub H/k/sub D/ = 1.05 and log k/sub xp/k/sub H/ = 0.25 sigma⁺) do not support the mechanism. Instead, they can be construed to support the previously validated mechanism of nucleophilic triggering of sigmatropic rearrangement

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[en] Claisen condensation of diacetylated fused aromatic and heteroaromatic compounds (fluorene, dibenzofuran, dibenzothiophene, or carbazole) with polyfluorocarboxylic acids esters in the presence of bases has afforded the ligands containing two β-diketonate groups. Their complexation with Eu³⁺ ions has been studied by the luminescence spectral method.

[en] In previous work, Conrad, using α-2⁰ deuterium kinetic isotope effects (KIE), showed that variable transition states are involved in Cope and Claisen rearrangements, two groups of sigmatropic reactions. The variation could be understood in terms of substituents affecting the relative extents of bond making and bond breaking. The kinetics and KIEs have now been determined for rearrangements of allyl trimethyl silyl ketene actal (TMS-KA), diisopropyl allylamine-oxide (diamo), and 1,3- and 1,4-diphenyl-1,5-hexadienes. Measurements of KIE in the reaction of TMS-KA and diamo, have shown that the transition state of both these reactions involve much more bond breaking than bond making. Solvent and phenyl substituent effects have been measured for TMS-KA, and these verify a non-polar reaction with substantial bond cleavage. The origin of the behavior is discussed. Measurements of the activation free energies for Cope rearrangement of 1,3- and 1,4-diphenyl-1,5-hexadienes reveal parameters similar to that of 3-phenyl-1,5-hexadiene. The values are consistent with a theoretical model developed for substituent effects in these reactions

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No abstract available