Oct-2-yn-4-enoyl-CoA as a multifunctional enzyme inhibitor in fatty acid oxidation

Oct-2-yn-4-enoyl-CoA was found to be a multifunctional irreversible enzyme inhibitor in fatty acid oxidation mainly targeting mitochondrial trifunctional protein beta-subunit. It can also inactivate enoyl-CoA hydratase 2 and medium-chain acyl-CoA dehydrogenase. This study increased our understanding for the effect of acetylenic acids on fatty acid oxidation.     

Synthesis of 4-amino-substituted but-2-en-4-olides

Previously unknown 4-amino derivatives of spiro-annelated Δ²-butenolide were synthesized by the addition of various amines at the activated triple bond of 4-hydroxy-2-alkynoic esters. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2761–2770, December, 2005.     

Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide derivatives

Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).     

1-methyl-2-undecyl-4(1H)-quinolone as an irreversible and selective inhibitor of type B monoamine oxidase

The inhibitory compound of monoamine oxidase (MAO) activity was isolated from the CH(2)Cl(2) fraction of the fructus of Evodia rutaecarpa and identified as 1-methyl-2-undecyl-4(1H)-quinolone (1). Compound 1 showed a selective inhibition of type B MAO (MAO-B) activity with the IC(50) value of 15.3 microM using a substrate kynuramine, but did not inhibit type A MAO (MAO-A) activity. The kinetic analysis using Lineweaver-Burk plots indicated that compound 1 competitively inhibited MAO-B activity with the K(i) value of 9.91 microM. The inhibition of MAO-B by compound 1 was found to be irreversible by dialysis of the incubation mixture. These results suggest that compound 1 is a potent irreversible inhibitor of MAO-B, and may regulate catecholamine content in the neurons.     

Oxidative Cyclization of Lithium 4-Ethoxy-1,1,1-trifluoro-4-oxobut-2-en-2-olate

Russian Journal of Organic Chemistry - Diethyl 2,5-dihydroxy-2,5-bis(trifluoromethyl)tetrahydrofuran-3,4-dicarboxylate has been synthesized for the first time by reaction of lithium...     

A new synthesis of 4-methoxy-cyclopent-2-en-1-ones

4-methoxy-cyclopent-2-en-1-ones $\text{6}$ are easily obtained through a simple procedure involving in the key-step the conversion of 2-furylcarbinols $\text{1}$ into 1,1,2-trimethoxy-al-kan-4-ones $\text{3}$, a masked form of 1,4-dicarbonyl compounds, by treatment with Amberlyst H15 in methanolic solution. Then, the regeneration of the aldehydic function and a base-catalysed aldolic condensation lead in high yields to the final products $\text{6}$.     

Efficient synthesis of 3-aminocyclobut-2-en-1-ones: squaramide surrogates as potent VLA-4 antagonists

A novel series of uniquely functionalized 3-aminocyclobut-2-en-1-ones has been prepared by facile condensation of a variety of cyclobuta-1,3-diones with a phenylalanine-derived primary amine. These systems subsequently lend themselves to substitution at C-2 by reaction with a variety of electrophilic reagents including N-halosuccinimides, sulfenyl chlorides, and Eschenmoser's salt. Compounds from this novel series are potent antagonists of VLA-4. [reaction: see text]     

Neocucurbitacin D,a novel lactone-type norcucurbitacin as xanthine oxidase inhibitor from Herpetospermum pedunculosum

Abstract

A novel lactone-type norcucurbitacin, designated as neocucurbitacin D (1), together with five known cucurbitane triterpenes were isolated from traditional Tibetan medicine “Se Ji Mei Duo”, which is the seed of Herpetospermum pedunculosum (Ser.) C.B. Clarke. The structure of neocucurbitacin D was elucidated by spectroscopic analysis, including 2D NMR and X-ray techniques. Compounds 1–6 were screened for their xanthine oxidase (XOD) inhibitory activity. Compound 1, 2 and 4 exhibited significant XOD inhibition with IC₅₀ values ranging from 10.16 to 18.41?μM. The absolute stereochemistry and XOD inhibitiory activity of lactone-type norcucurbitacins was reported firstly.     

3R,4R-dihydroxy-L-proline: a potent and specific β-D-glucuronidase inhibitor

The title compound, a naturally-occurring amino acid found in virotoxins, competitively inhibits bovine β-D-glucuronidase but does not affect other glycosidases.     

Palladium-catalyzed coupling of 2-en-4-yne carbonates with terminal alkynes

The first palladium-catalysed coupling of the carbonates of (E)-configured conjugated enynols with terminal alkynes is described. This method allows the synthesis of vinyl-allenynes with good yields. It has been determined that the method is not suitable for the (Z)-configured substrates.     

New method of isolating N-substituted 3-aminomethylenethiol-4-en-2-ones

The methods for the synthesis of the little-studied N-substituted 3-aminomethylenethiol-4-en-2-ones (I) — thiophene analogs of aromatic o-hydroxyazomethines — are based on the application of the not readily accessible and labile hydroxy and methoxy derivatives of thiophene [1, 2].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 854–855, June, 1986.     

Pyridines from azabicyclo[3.2.0]hept-2-en-4-ones through a proposed azacyclopentadienone

Pyridines have been formed by heating azabicyclo[3.2.0]hept-2-en-4-ones in toluene. The generation of a 3-azacyclopentadienone intermediate via a [2 + 2]-cycloreversion is proposed as the key step. A Diels-Alder reaction of a styrene, extrusion of carbon monoxide, and loss of hydrogen then gives the pyridine. The process parallels the well-known synthesis of benzenes from cyclopentadienones. The azabicyclo[3.2.0]hept-2-en-4-ones were synthesized from the reaction between readily available cyclopropenones and 1-azetines, in which the cyclopropenones behave as all-carbon 1,3-dipolar equivalents.     

Synthesis of Ethyl (2E)-5-Phenylpent-2-en-4-ynoate

Russian Journal of Organic Chemistry - An efficient procedure has been developed for the synthesis of ethyl (2E)-5-phenylpent-2-en-4-ynoate by olefination-dehydrohalogenation of...     

Nucleophilic sulfanylation of 1,5-disubstituted pent-2-en-4-yn-1-ones

Regioselectivity of nucleophilic addition of benzenethiols and phenylmethanethiol to 1,5-diarylpent-2-en-4-yn-1-ones in ethanol in the presence of triethylamine at 0–30°C is determined by the nucleophile nature. Phenylmethanethiol adds to the double bond, whereas benzenethiols add to the triple bond. The addition products, 1,5-diaryl-3-benzylsulfanylpent-4-yn-1-ones and 1,5-diaryl-5-(4-arylsulfanyl)penta-2,4-dien-1-ones, respectively, were isolated in 43–89% yield. Substituents in the aryl rings of the substrates did not affect the reaction direction.     

A convenient preparation of (S)-(−)-4-hydroxy-2-methylcyclopent-2-en-1-one and its application as a chiral synthetic equivalent of 2-methylcyclopent-2-en-1-one in the terpenoid synthesis

A method for the preparation of (S)-4-hydroxy-2-methylcyclopent-2-en-1-one from 1-(2-furyl)ethanol using modified Piancatelli rearrangement and enzymatic kinetic resolution of the racemate was developed. An application of O-protected derivatives of 4-hydroxy-2-methylcyclopent-2-en-1-one to terpenoid synthesis through tandem conjugate addition of allyl-metal reagents, enolate trapping, and consecutive Mukaiyama–Michael addition was studied. An optically active azulene derivative useful for terpenoid synthesis was efficiently synthesized.