Jari Yli-Kauhaluoma

Acetylcholinesterase inhibitory guided fractionation of Melissa officinalis L.

The plant Melissa officinalis L. has been used traditionally in the treatment of cognitive dysfunction. Based on its traditional medicinal use, it was assessed for its clinical efficacy in mild to moderate Alzheimers patients. The plant was effective in the management of the disease. Therefore, based on this result, a similar plant extract was prepared in order to be screened for bioactivities which are relevant in Alzheimers disease therapy. The extract was recently screened for antioxidant activity and it showed a wide range of antioxidant properties. Another important bioactivity is acetylcholinesterase inhibition, which the extract was screened for in the current investigation. The extract was capable of inhibiting the enzyme in a time and dose-dependent manner. Activity of the extract at 10 min was estimated as 1.72+/-0.16 microg equivalents of physostigmine/mg of the extract. Acetylcholinesterase inhibitory guided fractionation of the extract was then carried out. Most of the fractions showed inhibitory activity and were more potent than the extract. The contents of the most potent fraction were identified as cis- and trans-rosmarinic acid isomers and a rosmarinic acid derivative using LC-DAD-ESI-MS and NMR methods.

Solid-Phase Synthesis of Amino Acid Derived N-Unsubstituted Pyrazoles via Sydnones

A new method to synthesize N-unsubstituted pyrazoles on a solid support is described. The solid support acts as a protecting group for the amino acid. N-Protected amino acid is N-nitrosated, and the subsequent treatment with acetic anhydride in a microwave reactor yields mesoionic sydnones that react in situ in 1,3-dipolar cycloaddition reactions with alkynes. Traceless cleavage of the products gives N-unsubstituted pyrazoles in high overall yields.

Recent advances in 1,3-dipolar cycloaddition reactions on solid supports

Solid-phase methods are of a great significance in organic synthesis. Recent developments of these methods are providing new ways to construct libraries of small organic molecules. Five-membered heterocyclic compounds, which can be utilized in a variety of applications, are formed in the 1,3-dipolar cycloaddition reaction between dipolarophiles and dipoles. This review deals with the solid-phase synthesis of heterocycles via [3+2] cycloaddition reaction. Cycloaddition reactions of polymer-bound dipoles and polymer-bound dipolarophiles and intramolecular solid-phase cycloadditions are discussed in separate sections. Reactions of dipolarophiles such as alkenes, alkynes, and imines with dipoles such as azomethine ylides, azomethine imines, nitrile imines, azides, nitrones, and nitrile oxides are described. The recent literature up to December 2003 is covered.

Anti-leishmanial activity of betulin derivatives.

Leishmanicidal activity of 24 derivatives of naturally occurring and abundant triterpenes belonging to the lupane series, betulin, betulinic acid and betulonic acid, is described in this study. The easily modified positions of the lupane skeleton, the hydroxy groups of C-3 and C-28, as well as the carbon–carbon double bond C-20–C-29 were used as a starting point to prepare a library of triterpenoid derivatives for bioactivity studies. The compounds were evaluated against Leishmania donovani axenic amastigotes on a microplate assay at 50u2009μM. GI50 values of the most effective compounds were evaluated, as well as their cytotoxicity on the human macrophage cell line THP-1, and anti-leishmanial activity against L. donovani-infected THP-1 macrophages was determined. Betulonic acid was the most potent derivative, yielding a GI50 value of 14.6u2009μM. Promising and distinct structure–activity relationships were observed, and these compounds can be regarded as significant lead molecules for further improvement and optimization.

Benzo[cd]azulene Skeleton: Azulene, Heptafulvene, and Tropone Derivatives

Due to our interest in protein kinase modulating compounds, we developed syntheses for benzo[cd]azulenes. By using very common catalysts and reagents, such as t-BuOK, HCl, and mCPBA, the commercially available guaiazulene is converted in three steps into tricyclic tropone derivatives. Electrophilic aromatic substitution reactions of guaiazulene proceed without a catalyst. Complex one-pot reactions convert 1-hydroxyalkyl azulenes into tricyclic heptafulvenes, and finally, the mild oxidant mCPBA cleaves the semicyclic C horizontal lineC double bonds to furnish tropones.

2-Ethyl-1,3-dioxo-2,3,3a,4,7,7a-hexahydro-1H-isoindole-4-carboxylic acid

The Diels–Alder cycloxadaddition reactions between deactivated dienes and electron-deficient dienophiles are generally known to be thermodynamically disfavoured but when low solvent volumes were used for the reaction, the cycloxadaddition of 4-(bromoxadmethxadyl)phenoxyxadmethyl polystyrene-bound (E)-1,3-butadiene-1-carboxylic acid with N-ethylxadmaleimide gave the title compound, C11H13NO4, in good yield. The molxadecules are connected through hydrogen bonds between the carboxyl group and one exocyclic carbonyl oxygen. The title compound is interxadesting in medicinal chemistry since related compounds are known to increase the blood platelet count in thrombocytopenia and to possess antixadconvulsant activity.