Stefano Chimichi

Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies.

Natural geiparvarin 1 and a number of its analogues were prepared and tested as inhibitors of both monoamine oxidase isoforms, MAO-B and MAO-A. The desmethyl congener 6 of geiparvarin, proved potent and selective MAO-B inhibitor (pIC(50)=7.55 vs 4.62). X-ray crystallography and molecular modelling studies helped the understanding of the observed structure-activity relationships.

New geiparvarin analogues from 7-(2-oxoethoxy)coumarins as efficient in vitro antitumoral agents

A new class of compounds analogues of geiparvarin is described: aldolic condensation of 3(2H)-furanones and 7-(2-oxoethoxy)coumarins followed by a very efficient dehydration protocol led to the title compounds which show good antitumoral activity against several human cell lines.

The reactivity of 3-methyl-4-nitro-5-styrylisoxazole with some bis-enolisable ketones

The expected Michael adducts and spiroisoxazolines are obtained from the reaction between 3-methyl-4-nitro-5-styrylisoxazole and bis-enolisable ketones. Contrary to reported data, Michael adducts are obtained in good yields only when a substoichiometric amount of base is used, whereas spiroisoxazolines were obtained as the major product when the base is present in a large excess.

New 5-(2-ethenylsubstituted)-3(2H)-furanones with in vitro antiproliferative activity

Abstract A convenient route to new 3(2H)-furanones is described through hydrogenolysis and subsequent acidic hydrolysis of isoxazoles. The antiproliferative activity of title compounds were evaluated against leukemia-, carcinoma-, neuroblastoma-, and sarcoma-derived human cell lines in comparison to the natural compound geiparvarin. The structure activity relationship indicated that the maximum in vitro antiproliferative activity correlates with the presence of a heterocyclic ring on the ethenyl moiety.

A new convenient route to 2-oxoethoxycoumarins: key intermediates in the synthesis of natural products

A new synthetic route to coumarinyloxyaldehydes starting from hydroxycoumarins is presented; these compounds, useful intermediates in the preparation of natural products such as geiparvarin and psoralens, are now available in excellent yields with a simple workup procedure. Moreover the reported route has been applied to dihydroxycoumarins.

Complete assignment of the 1H and 13C NMR spectra of secoisolariciresinol diglucoside, a mammalian lignan precursor isolated from Linum usitatissimum

A convenient isolation and purification protocol for secoisolariciresinol diglucoside (1), a precursor of the biologically active mammalian lignans enterolactone and enterodiol, from flax seed is reported together with an extensive 1D‐ and 2D‐NMR study (GE‐HSQC, GE‐HMBC and NOESY) leading to its definitive characterization as 2,3‐bis[(4‐hydroxy‐3‐methoxyphenyl)methyl]‐1,4‐butanediyl bis‐[R‐(R*,R*)]‐β‐D‐glucopyranoside. Copyright

A convenient synthesis of psoralens

An efficient synthesis (yields >70%) of linear 7H-furo[3,2-g]chromen-7-one derivatives (psoralens or furocoumarins) has been carried out starting from ring-substituted 2-(coumarin-7-yl)oxyaldehydes; moreover, the phototoxicity of these compounds has been tested on a cultured cell line of murine fibroblast.

Pyrazolo[1,5-a]pyrido[3,4-e]pyrimidine : a new heterocyclic ring system

Treatment of 6-acetyl-7-(2-dimethylaminovinyl)pyrazolo[1,5a]pyrimidine (1) with hydroxylamine afforded in high yields the pyridine N-oxide (2), a key intermediate in the preparation of new functionalized pyrazolo[1,5-a]pyrido[3,4e]pyrimidine as well as in the synthesis of the parent ring system (8)

A new entry to pyrazolo[1,5-a]pyrido[3,4-e]pyrimidine derivatives

Treatment of 3-aminopyrazoles derivatives with 3-ethoxymethylenpentane-2,4-dione afforded new pyrazol[1,5-a]pyrimidines derivatives which were then converted into enamines by reaction with dimethylformamide dimethyl acetal; ring closure of these latter compounds led to pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines

GIAO DFT 13C/15N chemical shifts in regioisomeric structure determination of fused pyrazoles.

The combined use of two‐dimensional NMR correlation experiments and gauge including atomic orbital density functional theory in 13C NMR chemical shift (CS) calculations allowed reliable and simple structural determination of regioisomeric heterocyclic systems that originate from the reactions of acylquinolinones with substituted hydrazines. Moreover, the results of differential analysis between the calculated 15N NMR CSs for hypothetical structures and the experimental data of the title azaheterocyclic systems were even more advantageous with respect to 13C because there was no need for correlational analysis: structures of the regioisomeric compounds could be determined just by direct comparison. Copyright