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Reaction control in synthetic organic photochemistry: Switching between [5+2] and [2+2] Modes of Cycloaddition

Split personality: Reaction conditions that enable powerful control over the mode of photocycloaddition in maleimides have been developed. Direct irradiation favors the [5+2] mode whereas sensitized irradiation allows a complete switch to the [2+2] mode (see scheme; TBS=tertbutyldimethylsilyl).

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P-chirogenic silylphosphine-boranes: Synthesis and phospha-Michael reactions

Chiral and achiral silylphosphine-boranes were prepared in high yields by reaction of phosphide boranes with halogenosilanes. Their reaction at room temperature with Michael acceptors afforded 1,4-addition products as silylenol ether or ketone derivatives in good to excellent yields. In the case of the 2,3-dihalogeno-maleimides, the double addition of silylphosphine-borane led to the corresponding trans-diphosphine-boranes in 86% yield. Noteworthy, the reaction of Pchirogenic silylphosphine-boranes with enones afforded the phospha-Michael adducts without racemization at the P-center. While the silylphosphine-boranes have been scarcely described so far, these compounds demonstrate their great interest for the synthesis of chiral and achiral functionalized organophosphorus compounds.

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A protecting group free synthesis of (¡À)-neostenine via the [5 + 2] photocycloaddition of maleimides

(Chemical Equation Presented) A concise, linear synthesis of the Stemona alkaloid (¡À)-neostenine is reported. Key features include an organocopper-mediated bislactone C2-desymmetrization for the stereoselective construction of the cyclohexane-lactone C,D-rings. The assembly of the fused pyrrolo[1,2-a]azepine core was achieved by application of a [5 + 2] maleimide photocycloaddition. A custom FEP flow reactor was used to successfully overcome the scale limitations imposed by a classical immersion well batch reactor. The synthesis was completed in 14 steps from furan, in 9.5% overall yield, without the use of any protecting groups.

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Potent Bacterial Mutagens Produced by Chlorination of Simulated Poultry Chiller Water

Hypochlorite treatment of a simulated food-processing mixture produces 3,4-dichloromaleimide and 3,3-dichloro-4-(dichloromethylene)-2,5-pyrrolidinedione (C5HCl4NO2). The tetrachloro compound and two analogs, which can be synthesized from citraconic anhydride and itaconic anhydride, are direct-acting Ames mutagens in Salmonella typhimurium TA100 tester strain. These novel five-carbon cyclic imides are structurally similar to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the principal mutagenic compound present in paper pulp bleaching liquors. Molecular structure analysis of the mutagens was based on X-ray crystallography, 13C NMR, and mass spectrometry of synthetic chlorinated imides with identical mass spectra and gas chromatographic retention indices. The tetrachloroimide accounts for much of the mutagenicity of the dichloromethane-extractable pH 2 fraction from chlorination of a simulated food-processing system consisting of chicken frankfurters. In the Ames TA100 tester strain it has a molecular mutagenicity of 1450 revertants/ nmol without microsomal activation, making it the second most potent mutagen reported from a chlorination process.

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Novel Maleimide-type Acceptors Based on Annelated 1,4-Dithiins

Bis(tetraethylammonium) bis(2-thioxo-1,3-dithiole-4,5-dithiolato)zincate(II) 5 reacted with a range of 3,4-dichloromaleimides 4 (R=H, alkyl, aryl) to give a new annelated 1,4-dithiin system 6 in high yield.Oxidation of the thiones 6 gives the corresponding <1,3>-dithiolones 7.Cyclic voltammetry indicates that the new compounds are electron acceptors.

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A general approach to the synthesis of bisindolylmaleimides: Synthesis of staurosporine aglycone

Bisindolylmaleimides are prepared in 65-95% yield by reaction of an indole Grignard with either 2,3-dichloro-N-methylmaleimide or 2,3-dichloromaleimide. A one-step synthesis of arcyriarubin A in 72% yield affords ready access to the staurosporine aglycone.

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Rapid access to azepine-fused oxetanols from alkoxy-substituted maleimides

UV irradiation of alkoxy-substituted N-alkenylmaleimides induces a sequence involving a [5 + 2] cycloaddition followed by a Norrish-Yang cyclization. The resulting highly strained alkylidene oxetanol-fused azepines are formed in good yield and with high diastereoselectivities.

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Natural product-based pesticide discovery: Design, synthesis and bioactivity studies of N-amino-maleimide derivatives

Natural products are an important source of pesticide discovery. A series of N-amino-maleimide derivatives containing hydrazone group were designed and synthesized based on the structure of linderone and methyllinderone which were isolated from Lindera erythrocarpa Makino. According to the bioassay results, compounds 2 and 3 showed 60% inhibition against mosquito (Culex pipiens pallens) at 0.25 mug¡¤mL?1. Furthermore, the results of antifungal tests indicated that most compounds exhibited much better antifungal activities against fourteen phytopathogenic fungi than linderone and methyllinderone and some compounds exhibited better antifungal activities than commercial fungicides (carbendazim and chlorothalonil) at 50 mug¡¤mL?1. In particular, compound 12 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 11 phytopathogenic fungi) and compounds 12 and 14 displayed 60.6% and 47.9% inhibitory activity against Rhizoctonia cerealis at 12.5 mug¡¤mL?1 respectively. Furthermore, compound 17 was synthesized, which lacks N-substituent at maleimide and its poor antifungal activity against Sclerotinia sclerotiorum and Rhizoctonia cerealis at 50 mug¡¤mL?1 showed that the backbone structure of N-amino-maleimide derivatives containing hydrazone group was important to the antifungal activity.

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<2 + 2> Photocycloadditions of Dichloromaleimide and Dichloromaleic Anhydride to Cyclic Olefins

The photocycloaddition of dichloromaleimide to cyclohexadiene, cyclopentadiene, and cyclopentene on direct photolysis gave <2 + 2> addition products with the cis,endo- and cis,exo-configurations as the major products.However, a similar photocycloaddition to cyclohexene yielded the trans-fused cycloaddition product (between the four- and six-membered rings) as the major product in addition to the cis,endo- and cis,exo-isomers.The photocycloadditions of dichloromaleic anhydride to cyclopentadiene and cyclohexadiene were reinvestigated; two major products were obtained which were identified as the cis,endo- and cis,exo-addition products, while the reported trans-fused isomers were not isolated.The structures of these photoaddition products were investigated by 400 MHz n.m.r. spectroscopy to ascertain the configuration of the ring fusion.An X-ray crystallographic analysis established the stereochemistry of one product.

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Halogenated 2,5-pyrrolidinediones: Synthesis, bacterial mutagenicity in Ames tester strain TA-100 and semi-empirical molecular orbital calculations

The chloroimide 3,3-dichloro-4-(dichloromethylene)-2,5-pyrrolidinedione, a tetrachloroitaconimide, is the principal mutagen produced by chlorination of simulated poultry chiller water. It is the second most potent mutagenic disinfection by-product of chlorination ever reported. Six of seven new synthetic analogs of this compound are direct-acting mutagens in Ames tester strain TA-100. Computed energies of the lowest unoccupied molecular orbital (ELUMO) and of the radical anion stability (DeltaHf/rad – DeltaHf) from MNDO-PM3 for the chloroimides show a quantitative correlation with the Ames TA-100 bacterial mutagenicity values. The molar mutagenicities of these direct acting mutagenic imides having an exocyclic double bond fit the same linear correlation (lnMm vs. ELUMO; lnMm vs. DeltaHf/rad – DeltaHf) as the chlorinated 2(5H)-furanones, including the potent mutagen MX, 3-chloro-4-(dichloro-methyl)-5-hydroxy-2(5H)-furanone, a by-product of water chlorination and paper bleaching with chlorine. Mutagenicity data for related haloimides having endocyclic double bonds are also given. For the same number of chlorine atoms, the imides with endocyclic double bonds have significantly higher Ames mutagenicity compared to their structural analogs with exocyclic double bonds, but do not follow the same ELUMO or DeltaHf/rad – DeltaHf correlation as the exocyclic chloroimides and the chlorinated 2(5H)-furanones.

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