Trifluoroacetic acid: a more effective and efficient reagent for the synthesis of 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones and 3-arylmethyl-2-amino-quinolines from Baylis-Hillman derivatives via Claisen rearrangement

Trifluoroacetic acid has been discovered to be a highly effective and efficient reagent for the tandem Claisen rearrangement and cyclization reaction to yield 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones from compounds obtained from the S_N2 reaction between anilines and acetyl derivatives of Baylis-Hillman adducts of acrylates in the presence of DABCO. In contrast, similar compounds obtained from the acetyl derivatives of Baylis-Hillman adduct of acrylonitrile on treatment with trifluoroacetic acid directly furnish 3-arylmethyl-2-amino-quinoline via tandem Claisen rearrangement, cyclization and isomerization.     

Degradation of ²-O-4 lignin model and related compounds by the ascomyceteChrysonilia sitophila (TFB 27441 strain)

Growth of the ascomyceteChrysonilia sitophila during degradation of lignin model dimers and monomers was compared to a glucose control. An inhibition of growth by Cα-carbonyl monomers and stimulation by β-O-4 lignin model and vanillyl alcohol were observed. A comparison of the degradation by this ascomycete with the basidiomycetePhanerochaete chrysosoporium showed similarities in relation to the type of degradation caused.     

Studies of solvent effects

The effect of water on the conformational preferences of acetylcholine has been studied within the discrete, the continuum and the combined discrete-continuum models described in parts I and II of this series. All the models lead to the conclusion that the trans-gauche form which is, following refined quantum-mechanical computations, the intrinsically preferred one and the one observed in the crystal of acetylcholine and of a number of analogues should remain also the preferred conformation in water. This result agrees with NMR studies. The results of the empirical discrete model used here compare favorably to those obtained by an ab initio super-molecule treatment. The continuum model utilized here represents a net improvement above such models utilized in other works.     

Engineering cytochrome P-450s

Cytochrome P-450 isozymes represent a critical component of nature’s spectrum of detoxification catalysts that could be exploited for bioremediation. The ethanol-inducible human cytochrome P-450 2E1 serves as a model eukaryotic P-450 that complements the bacterial P-450 cam in dehalogenation and detoxification of environmental pollutants. We explored the construction of novel chimeric P-450s using cytochrome P-450 camC and 2E1 genes. For construction of chimera 1 (478 amino acids, 55.14 kDa), 145 amino acids from the N-terminus of P-450 2E1 protein (493 amino acids, 56.84 kDa) were replaced with 130 amino acids from the N-terminus of P-450 camC protein (415 amino acids, 46.66 kDa). In chimera 2 (525 amino acids, 60.24 kDa) the strategy involves replacement of 28 amino acids in the C-terminus of chimera 1 with 75 amino acids from the C-terminus of P-450 camC gene. Homology models of both the chimeric proteins were developed using SWISS-MODEL based on the known crystal structure of cytochrome P-450 camC, BM-3, 1DT6A, and 2C17A. The models indicated that the proposed heme-binding site was intact, which is inevitable for catalytic activity of cytochrome P-450s. The expression of chimera 1 and 2 genes in Escherichia coli DH5α was evident from light-pink cell pellets, protein band in sodium dodecyl sulfate polyacrylamide gel electrophoresis, and diagnostic carbon monoxide-difference spectra. Our studies show that strategies can be developed to exploit the natural diversity of the P-450 superfamily to generate chimeric biocatalysts that would provide new templates amenable to directed evolution.     

Synthesis, electrochemical and biological studies on polyfunctionalized 4-ferrocenyl-4H-pyran and 4-ferrocenyl-1,4-dihydropyridine derivatives

The first synthesis of polyfunctionalized 4-ferrocenyl-4H-pyran and 4-ferrocenyl-1,4-dihydropyridine derivatives, as well as some of their relevant properties, including an electrochemical study and some aspects of their biological profile have been described.     

Hydrogenation of ethyl esters of 4-phenyl-and (2-furyl)-substituted 2,4-dioxobutyric acids at palladium black

The hydrogenation of ethyl 4-R-2,4-dioxobutyrates (R = phenyl, 2-furyl) at 5% Pt/Al₂O₃ catalyst, modified with cinchonidine, and at palladium black was investigated. The former had low activity under the conditions we tested. The main products during the hydrogenation of these compounds at palladium black are ethyl 4-R-2-hydroxy-4-oxobutyrates. The yield of the phenyl derivative amounts to 68.5%, while the yield of the corresponding 2-furyl derivative amounts to 97%. In the last case ethyl 2-hydroxy-4-oxo-4-(2-tetrahydrofuryl)butyrate was detected as impurity. The optimum conditions for the formation of ethyl 2-hydroxy-4-phenylbutyrate (yield 88.2%) were determined. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 655–659, May, 2006.     

Synthesis ofS-(+)-hydroprene

A novel path toS-(+)-hydroprene (1) starting from the technical gradeS-(+)-dihydromyrcene (2, e.e. 50%) is proposed. The latter was selectively transformed intoS-3,7-dimethyloctanal (5) in three steps including hydroalumination. The reactions of5 with allyl- or methallylmagnesium chloride followed, respectively, either by oxygenation in the presence of PdCl₂/CuCl or by ozonolysis, affordS,E-6,10-dimethyl-3-undecen-2-one (7) which was treated with ethoxyethynylmagnesium bromide to give the title juvenile hormone analogue in 23% overall yield.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No 1, pp. 110–112, January, 1993.     

Correlation of the position of the bond functions in H-X with electronegativity

S type Gaussian bond functions are optimized for HF, H₂O, NH₃, and CH₄. The optimization is carried out with respect to the exponent and position in the H-X bond. The position is found to correlate well with the electronegativity of Pauling and Allred-Rochow.     

Recent Applications of α-Metalated Isocyanides in Organic Synthesis

Being both nucleophilic and electrophilic, α-metalated isocyanides can add to polar double bonds, forming heterocycles. They are also synthons for α-metalated primary amines. This article describes recent or improved procedures for their use in organic synthesis: (1) In heterocyclic syntheses to give 2-oxazolines, 2-imidazolines, 2-thiazolines, oxazoles and oligooxazoles, thiazoles, triazoles, imidazolinones, pyrroles, 5,6-dihydro-1,3-oxazines and -thiazines, and (via cycloaddition with nitrones) 2-imidazolidinones. (2) In the field of formylaminomethylenation, for example transformation of estrone methyl ether and a keto sugar into the corresponding α-formylaminoacrylic esters, and the conversion of aldehydes and ketones by 3- and 4-pyridyl-methyl isocyanides into N-(1-pyridyl-1-alkenyl)formamides and their hydrolysis to 3- and 4-acylpyridines. (3) In connection with the use of α-metalated isocyanides as synthons for α-metalated primary amines, the author demonstrates how they may be used for preparation of 1,2- and 1,3-amino alcohols, 1,2-diamines, 2,3-diaminoalkanoic acids and for synthesis of higher amino acids starting from simple amino acids.     

Synthesis of stable azomethine ylides by the rearrangement of 1,3-dipolar cycloadducts of 3,4-dihydroisoquinoline-2-oxides with DMAD

1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were prepared according to a one-pot procedure involving the reaction of 2-(3,4-dimethoxyphenyl)-ethylamine with aromatic aldehydes in TFA at reflux. The tetrahydroisoquinolines were treated with H₂O₂-WO₄²⁻ in methanol at room temperature to give the corresponding 3,4-dihydroisoquinoline-2-oxides. Treatment of these cyclic nitrones with DMAD in toluene at room temperature gave the corresponding isoxazolo[3,2-a]isoquinolines. These compounds were heated in toluene at reflux to give the corresponding ylides in high yields (Method A). The effect of the substituents on the rate of the rearrangement of such compounds prompted us to discuss a new mechanism involving consecutive C-C bond heterolysis and 1,3-sigmatropic shift. A one-pot reaction involving the treatment of the nitrones with equimolar amounts of DMAD in refluxing toluene also gave the ylides (Method B). The structures of the prepared compounds were elucidated by spectral means and elemental analyses.