Pilar López-Alvarado

Controlled Generation of Three Contiguous Stereocentres in the Michael Addition of 1-Pyrrolidinocyclohexene to (E)-(1-Methyl-2-oxoindolin-3-ylidene)acetophenone

Addition of 1-pyrrolidinocyclohexene to (E)-(1-methyl-2-oxoindolin-3-ylidene)acetophenone followed by acid hydrolysis was diastereoselectively controlled to give (±)-7a (3R*,1′S*,2′S*) or (±)-7b (3S*,1′R*,2′S*), the structures of which were supported by 1H NMR spectroscopic data and corroborated by X-ray diffraction analysis. The change in configuration at the C-2′ centre greatly affected the geometries of the two diastereomers, both in solid and in solution. An explanation of the observed diastereoselectivity is provided. An approach to the N-methylwelwitindolinone C skeleton from 7b as a starting material, by insertion of a rhodium carbenoid into the C(4)−H indole position, was abandoned because of the initial experimental results, which are also described. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

N-Arylation of azoles and their benzo derivatives by p-tolyllead triacetate

Abstract The N-arylation of a variety of azoles and their benzo derivatives was achieved by treatment at 90–100 °C with p-tolyllead triacetate in the presence of copper (II) acetate.

Discovery of a class of diketopiperazines as antiprion compounds.

Prion diseases are fatal neurodegenerative and infectious disorders for which effective pharmacological tools are not yet available. This unmet challenge and the recently proposed interplay between prion diseases and Alzheimers have led to a more urgent demand for new antiprion agents. Herein, we report the identification of a novel bifunctional diketopiperazine (DKP) derivative 1 d, which exhibits activity in the low micromolar range against prion replication in ScGT1 cells, while showing low cytotoxicity. Supported by properly addressed molecular modeling studies, we hypothesized that a planar conformation is the major determinant for activity in this class of compounds. Moreover, studies aimed at assessing the mechanism‐of‐action at the molecular level showed that 1 d might interact directly with recombinant prion protein (recPrP) to prevent its conversion to the pathogenic misfolded prion protein (PrPSc)‐like form. This investigation suggests that DKP based antiprion compounds can serve as a promising lead scaffold in developing new drugs to combat prion diseases.

Solvent effects on the fluorescent emission of some new benzimidazole derivatives

Abstract The benzimidazole moiety is present in a great variety of pharmaceutical compounds with anthelmintic action and other applications. These compounds exhibit native fluorescence which often depends on the substituents on the benzimidazole ring and the solvents. The fluorescence emission also changes with pH. In this article the solvatochromic effect is described in different solvents (polar protic and aprotic, alkanes, pyridine and acetic acid) of a series of new benzimidazole derivatives, namely 1-methyl-6-nitro-benzimidazole (6-NBI), 1-methyl-6-aminobenzimidazole (6-ABI) and 1-methyl-6-(p-tolylamino)benzimidazole (6-TABI). The fluorescence intensity is weaker for 6-NBI than for the other derivatives in all solvents tested due to quenching of fluorescence emission by the nitro group. The excitation and emission wavelengths are red shifted for 6-TABI with respect to those observed for 6-NBI and 6-ABI, due to the presence of the tolyl group. The fluorescence emission maximum is shifted for 6-ABI from λem = 362 nm in formic acid to λem = 470 nm in pyridine; this behaviour is explained in terms of the acid-base characteristics of these compounds. A remarkable shift in the emission wave-length can be also observed for 6-ABI with changing solvent polarity from 354 nm in alcohols to 420 nm in dimethyl sulphoxide. This behaviour could be related to the different equilibria that take place in the excited state, i.e., acid-base equilibria and also charge transfer processes, depending on the solvents.

EFFICIENT, MULTIGRAM-SCALE SYNTHESIS OF THREE 2,5-DIHALOBENZOQUINONES

ABSTRACT 2,5-Dibromo-, 2,5-dichloro- and 2,5-diiodobenzoquinone were conveniently prepared from 1,4-dimethoxybenzene in 87%, 97% and 84% overall yields. None of the two steps of the synthesis required purification.

SILICA GEL-SUPPORTED HETERO DIELS-ALDER REACTIONS OF QUINOLINETRIONES

When 2,5,8(1H)-quinolinetriones were supported on silica gel and treated with 1-dimethylamino-1-azadienes in excess, followed by rapid chromatography, the corresponding 5,8-dihydro-1,8-diazaanthracene-2,9,10-triones or 1,8-diazaanthracene-2,9,10-triones were obtained, normally in excellent yields. This procedure minimizes or completely prevents the addition of dimethylamine to the starting quinone, a problem that has seriously limited in the past the usefulness of 1-dimethylamino-1-azadienes as heterodienes for quinones.

Versatile synthesis of malonamic acid derivatives from a β-ketothioester

An efficient synthetic route is described that allows the preparation under mild conditions of several types of malonamic acid derivatives. The S-tert-butyl acetothioacetate monoanion reacted with aryl or alkyl isocyanates to give β-amidothioesters in one step and 73–87% yield, after spontaneous deacetylation of tricarbonyl intermediates. Treatment of these thioesters with several aliphatic or aromatic alcohols and amines at room temperature in THF or DME and in the presence of silver trifluoroacetate provided, respectively, the corresponding malonamic acid esters and malonamides in 80–100% yield.

Total synthesis of diazaquinomycin A

Abstract Two concise total syntheses of the diazaanthraquinone antibiotic diazaquinomycin A are reported. The first route features a double hetero Diels-Alder reaction between 2,6-dibromobenzoquinone and 2-methyl-2-hexenal dimethylhydrazone, aromatiztion by a novel, one-pot N-oxidation/elimination procedure with percarbamide in trifluoroacetic acid, and double N -oxidation followed by rearrangement to a double lactam system. The key step of the second route is a hetero Diels-Alder reaction between 2-methyl-2-hexenal dimethylhydrazone and 3-methyl-4-propyl-1 H -quinoline-2,5,8-trione.

Regioselective Diels–Alder reactions of 3-indolylquinones

Abstract 6-(3-Indolyl)quinolinequinone derivatives gave regioselective Diels–Alder reactions with a variety of dienophiles, yielding polycyclic carbazole derivatives. One-pot reactions, proceeding through a cascade of reactions including regioselective Michael and Diels–Alder steps, gave heptacyclic derivatives starting from indoles and 2,5,8(1 H )-quinolinetriones. Double Diels–Alder reactions of 6-(3-indolyl)quinolinequinones and dihalobenzoquinones gave eleven-cycle products in one step.

One-pot assembly of large heterocyclic quinones through three-component reactions

Abstract Treatment of indoles with 2,5,8-quinolinetriones in the presence of a catalytic amount of hydrochloric acid afforded heptacyclic reaction products arising from a cascade of two regioselective Michael addition–Diels–Alder cycloaddition steps. In another approach to polyheterocyclic quinone systems, double Diels–Alder reactions between indolylquinolinetriones and 2,5- or 2,6-dihalogenated benzoquinones provided regioisomeric 11-cycle products in good yields.