Enantio- and diastereoselective total synthesis of EI-1941-1, -2, and -3, inhibitors of interleukin-1beta converting enzyme, and biological properties of their derivatives

[reaction: see text] The first asymmetric total synthesis of EI-1941-1, -2, and -3, inhibitors of the interleukin-1beta converting enzyme (ICE), has been accomplished, starting from a chiral epoxy iodoquinone 11, a key intermediate in our total synthesis of epoxyquinols A and B. Despite a failure to synthesize the inhibitors by our postulated biosynthetic route, we were able to diastereoselectively synthesize them via an intramolecular carboxypalladation with the key steps being a 6-endo cyclization mode followed by beta-hydride elimination. The investigation of the biological properties of EI-1941-1, -2, and -3 and their derivatives disclosed them to be potent and effective ICE inhibitors with less cytotoxicity than EI-1941-1 and -2 in a cultured cell system.     

Inhibiting olefin cis, trans-photoisomerization and enhancing electron-accepting ability of a diboryl compound by metal chelation

To examine the impact of metal chelation on cis-trans olefin bond isomerization and the photo-stability of N,C-chelate photochromic boron compounds, a new π-conjugated molecule B-BPY that incorporates a 2,2'-bipy unit, two olefin bonds, and two BMes(2)(ppy) chromophores has been synthesized and found to stabilize the molecule toward olefin photoisomerization upon binding with a metal ion.     

Synthesis of derivatives of 1, 2, 4-triazole-3, 5-dicarboxylic acid

By oxidation of 3,5-dimethyl-1,2,4-triazole the monopotassium salt of 1,2,4-triazole-3,5-dicarboxylic acid was obtained. The mononitryl of 1,2,4-triazole-3,5-dicarboxylic acid was isolated during the reaction between 3-diazo-1,2,4-triazole-5-carboxylic acid and potassium cyanide in the presence of copper cyanide. Acid hydrolysis of 3-cyano-1,2,4-triazole-5-carboxylic acid leads to the formation of 3-carbamido-5-carboxy-1,2,4-trlazole, which on esterification with methanol gives rise to 3-carbamido-5-carbomethoxy-1,2,4-triazole.     

The ring-chain equilibrium in derivatives of 5-nitro-1, 2, 3, 4-tetrahydropyrimidine in trifluoroacetic acid

¹H NMR spectra of derivatives of 5-nitro-1,2,3,4-tetrahydropyrimidine were examined in trifluoroacetic acid solution. It was found that the compounds, unsubstituted in position 2, preserve their ring structure, whereas 2-alkyl- and 2-aryl derivatives are subjected to ring opening.     

Catalytic route to the synthesis of optically active beta,beta-difluoroglutamic acid and beta,beta-difluoroproline derivatives

Beta,beta-difluorinated amino acid derivatives were synthesized via Mg(0)-promoted defluorination of alpha-trifluoromethyl iminoester. Bromination of the difluoroenamine afforded the bromodifluoromethyl iminoester in good yield. Pd-catalyzed asymmetric hydrogenation of the bromodifluoromethyl iminoester and the subsequent transformations provided optically active beta,beta-difluoroglutamic acid and beta,beta-difluoroproline derivatives.     

1-Hydroxy-2-Aminoisopropylphosphonic acid and its derivatives

Conclusions Reduction of O,O-dialkyl-1-hydroxy-2-nitroisopropylphosphonates has yielded the corresponding amino derivatives. Their hydrolysis leads to formation of 1-hydroxy-2-aminoisopropylphosphonic acid.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, p. 179, January, 1969.     

Synthesis of 2S, 3aS, 7aS- and of 2S, 3aR, 7aR-Perhydroindole-2-carboxylic acid derivatives from L-aspartic acid

Using carbon radicals generated by photolysis of N-hydroxy-2-thio-pyridone esters (mixed anhydrides) the chiral centre of L-aspartic acid has been easily incorporated into the perhydroindole structure of the title compounds.     

Pyrolysis of 3-hydroxy-2-arylhydrazonoalkanoic acid derivatives

1,2-Diaza-1,3-butadienes have been obtained from readily available 3-hydroxy-2-arylhydrazonopropanoates under various reaction conditions including pyrolysis, dehydration under Mitsunobu conditions or with acetic anhydride or acetic acid. According to their method of synthesis these 1,2-diaza-1,3-butadienes underwent subsequent reactions to give interesting products, and in the presence of proper dienophiles gave the corresponding cycloaddition products. Also, a new approach to pyrazole-3-carboxylic acid derivatives was discovered during an attempt to dehydrate 3-hydroxy-2-arylhydrazonobutanoic esters.     

Spectral properties and inclusion of 3-(4'-dimethylaminophenyl)-1-(2-furanyl)prop-2-en-1-one in organized media of micellar solutions, beta-cyclodextrin and viscous medium

On the line of a previous work on the spectral properties of some of heteroaryl chalcone, the absorption and fluorescence emission spectral properties of 3-(4'-dimethylaminophenyl)-1-(2-furanyl)prop-2-en-1-one (DMAFP), have been investigated in organized media of aqueous micellar and beta-cyclodextrin (beta-CD) solutions. While the absorption spectra are less sensitive to the nature of the added surfactant or beta-CD, the characteristics of the intramolecular charge transfer (ICT) fluorescence are highly sensitive to the properties of the medium. The ICT maximum is strongly blue-shifted with a great enhancement in the fluorescence quantum yield on adding micellar or beta-CD. This indicates the solubilization of DMAFP in the micellar core and formation of an inclusion complex with beta-CD. The critical micelle concentrations (CMC) as well as the polarity of the micellar core of SDS, CTAB and TX-100 have been determined. The CMC values are in good agreement with the reported values while the polarity is lower indicating that DMAFP molecules are incorporated in the micellar core not at the micellar interface. The inclusion constants of binding of DMAFP in micellar or beta-CD have been also determined. The thermodynamic parameters of formation of DMAFP:CD inclusion complex have been calculated from the temperature dependence of the fluorescence spectra of the formed complex. The highly negative value of formation entropy (DeltaS=-98.0Jmol(-1)K(-1)) reflects the high restrictions imposed on the movement of both the host and included guest molecules which is consistent with the increase of the fluorescence yield and blue shift of the fluorescence maximum.     

Synthesis and some transformations of 1, 2, 3, 4-tetrahydrophenothiazine derivatives

1,2,3,4-Tetrahydrophenothiazine derivatives were obtained from cyclic monoketones and 1,3-diketones and o-nitroarenesulfenyl chlorides. The alkylation, aminomethylation, and oxidation of the compounds obtained were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1509–1513, November, 1972.     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid and β-heteroarylamino-α-amino acid derivatives

From heteroarylaminomethyleneoxazolones 4 , obtained from N-heteroarylformamidines 2 and 2-phenyl-5-oxo-4,5-dihydro-1,3-oxazole ( 3 ), the following β-heteroarylamino-α,β-dehydro-α-amino acid derivatives were prepared: methyl 8 and ethyl esters 9 , amides 10 and 11 , hydrazides 12 , and azides 15 . By catalytic hydrogenation the compounds 4 were converted into β-heteroarylamino substituted amides 18 and β-heteroarylamino-α-amino acids 20 .     

Asymmetric synthesis of new beta,beta-difluorinated cyclic quaternary alpha-amino acid derivatives

The synthesis of new beta,beta-difluorinated cyclic quaternary alpha-amino acid derivatives 1 in which a ring-closing metathesis reaction (RCM) constitutes the key step is described. The approach employs imidoyl chlorides 3 as fluorinated building blocks, and the overall process involves the stereoselective creation of a quaternary stereocenter. Complete selectivity was achieved when (R)-phenylglycinol methyl ether was used as chiral auxiliary, allowing for the preparation of new six-membered cyclic fluorinated alpha-amino acids as single enantiomers.     

Syntheses of 1-alkyl-2-acylindoles, 1-alkyl-2-acylindole-3-carboxylic acids,and their esters,in superbasic media

2-Acylindoles and 2-acylindole-3-carboxylic acids are readily alkylated at the nitrogen atom by haloalkanes in a superbasic medium (DMSO + NaOH). For the carboxylic acids, this reaction may proceed either entirely at the nitrogen atom, or at both the the nitrogen atom and the carboxyl group, depending on the content of water in the medium and the alkali -haloalkane ratio.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 472–482, April, 1996.     

1, 2, 4-Triazol-3-one and its nitro and amino derivatives

Some possible methods of preparation of 1, 2, 4-triazol-3-one are explored. A new method of preparing it from semicarbazide hydrochloride and formic acid is worked out. Nitration of the triazolone gives 5-nitro-1, 2, 3-triazol-3-one, whose structure is proved.     

Preparation of 1H,2H- and 1H-cyclopropene-3,3-dicarboxylic acid esters and 1H,2H-cyclopropene-3,3-dicarboxylic acid from the corresponding trimethylsilyl derivatives

Conclusion The feasibility was shown for use of the silyl protection method for the synthesis of 1H- or 2H-cyclopropene-3,3-dicarboxylic acids and their esters. The preparation of 1H,2H-cyclopropene-3,3-dicarboxylic acid and its dimethyl ester by this method was demonstrated for the first time.For the previous communication, see [1].Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2803–2805, December, 1986.     

Asymmetric synthesis of 2-amino-3-hydroxynorbornene-2-carboxylic acid derivatives

The enantioselective synthesis of 2-amino-3-hydroxynorbornene-2-carboxylic acid derivatives (5) was studied using the Diels-Alder reaction between cyclopentadiene and different dienophiles, i.e., alkyl 5-oxo-2-phenyloxazol-4-methylenecarbonates (1) or 2-benzoylamino-3-alkoxycarbonyloxy-acrylates (12), operating with different Lewis acids and both with thermal and with ultrasound conditions. The enantioselective synthesis of the exo/endo compounds 5c,d and 5'c,d was achieved starting from the chiral menthyl acrylates 12b,c using Mg(ClO(4))(2) as the catalyst and ultrasound. The cycloadducts were obtained in very good yield, in mild conditions, in short time, and in good diastereomeric excess (exo, 80%; endo, 87%). Finally, the use of alkylidene-oxazolones or acrylates and EtAlCl(2) or Mg(ClO(4))(2) as the catalyst allowed control of the cycloaddition reaction in favor of the exo or endo products.