Elizabeth Malamidou-Xenikaki

A Convenient Approach to Fused Indeno-1,4-diazepinones through Hypervalent Iodine Chemistry

Indenocarboxamides, resulting from the sequential addition of two arylamine equivalents to indanedione ketene dimer, are oxidized by [bis(trifluoroacetoxy)iodobenzene] to fused indeno-1,4-diazepinones in yields depending on the substituents on both aromatic rings. A plausible reaction pathway explaining the formation of the title compounds, as well as the formation of the two other minor products of the reaction, through a common intermediate, is suggested.

Formation and reduction reactions of 3-indo-3-yl-isoxazolidines

Abstract 1,3-Dipolar cycloaddition reactions of C-(1-methylindol-3-yl)-N-methylnitrone (1 with carbonyl substituted dipolarophiles lead to the formation of indolyl-isoxazolidines 3–6. Further reduction of the cycloadducts bearing a 5-methoxycarbonyl substituent give the pyroolidinones 8, 10. The stereoselectivity of the reactions and the structure elucidation of the product are discussed.

1-8H-pyrano[3,2-g]benzoxazol-8-ones from 7-methoxyimino-4-methylchromene-2,8-dione

Abstract 7-Methoxyimino-4-methylchromene-2,8-dione 3, easily prepared from the quinone 1 reacts thermally with methylaromatics 5(a–g), benzyl derivatives 13(a–c), halo derivatives 14(a–c) to give mainly oxazolocoumarins. Products 8(a–d) are obtained from 5(a–d), 13(a–c). Compound 9 is obtained from 5(a–c) and 13(a–c), compounds 15(a–c) are obtained from 14(a–c), the aminophenol 10 and coumarin 16 are obtained from 5f and 14c respectively, while coumarin 12 is obtained from 5g. The reaction of 3 with N-methyl-aniline and N,N-dimethylbenzylamine gives compound 10 and 8a respectively.

A study on the reactions of indol-3-yl-carbaldehyde oximes with electrophilic alkenes/alynes. Generation of nitrones from the O-H oximes. 4π-participation of the O-Me oximes in diels-alder reactions.

The reactions of indol-3-yl-carbaldehyde oximes with electrophilic alkenes/alkynes are studied. The O-H oximes 1 act as a Michael donors towards the electrophilic reagent affording the isoxazolidines 9, 10 through a tandem nitrone 8 generation - 1,3-dipolar cycloaddition process. The O-Me oximes 13 act as 1-aza-1,3-butadienes affording theγ-carbolines 16 and 19.

Preparation and catalytic hydrogenation of 1,2,4-oxadiazolo[4,5-a]indolines

Abstract 2,3,3-Trimethyl-3H-indole 1 reacts with nitrile oxides 2 to afford 1,2,4-oxadiazolo [4,5-a]indolines 3 in high yields. Catalytic hydrogenation of compounds 3 over Raney nicke results in the cleavage of the oxadiazole ring and gives almost quantitatively products 4 or 5.

Synthesis of 8,9-oxaza[5.3.3]Propell-9-en-2-ones via 1,3-dipolar cycloaddition of nitrile oxides to bicyclo[5.3.0]Dec-1(7)-en-2-one

Abstract The synthesis of the title heterocyclic propellanes is described. The cycloaddition is also examined on the basis of frontier molecular orbitals (FMO) of the reacting species.

A Survey on the Reactivity of Phenyliodonium Ylide of 2-Hydroxy-1,4-Naphthoquinone with Amino Compounds

The phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone reacts with aminoesters, ureas, aminoalcohols and aminophenols in refluxing dichloromethane to afford good yields of indanedione 2-carboxamido compounds, that in solution exist in an enol-amide form. The same reactants in a copper-catalyzed reaction afford mainly the corresponding N-arylo compounds. Arylhydrazines are mainly oxidized by the ylide and arylation occurs only in a low yield.

Indeno[1,2-d]pyrido[1,2-a]pyrimidines: a new class of receptor tyrosine kinase inhibitors.

Receptor tyrosine kinases (RTKs) are important mediators of signal transduction and play critical roles in cell growth, differentiation, metabolism, and apoptosis, and are deeply involved in oncogenesis. Binding of growth factors to the extracellular domains of RTKs leads to their dimerization, resulting in activation of the intracellular kinase domain, which eventually enables autophosphorylation at specific tyrosine residues. This family is also represented in oncogenic fusion proteins such as the Bcr-Abl protein of the Philadelphia chromosome. RTKs are organized into different families based on sequence homology and structural characteristics. There are more than 90 known protein kinase genes; 58 encode transmembrane receptor TKs distributed in 20 subfamilies, and 32 encode cytoplasmic non-receptor TKs distributed in 10 subfamilies. 2] Tyrosine kinases have been validated as suitable pharmacological targets for anticancer drugs, and several TK inhibitors have shown promising results in preclinical in vitro and in vivo models; others have been approved for the treatment in patients with cancer. This is best exemplified by the tyrosine kinase inhibitor imatinib (Gleevec), which has shown impressive activity against chronic myelogenous leukemia (CML) and has also been successful in the treatment of gastrointestinal stromal tumors, other leukemias, and solid tumors. The majority of the recently developed RTK inhibitors, including imatinib, target multiple mechanisms and are known as multiplex or multi-target tyrosine kinase inhibitors (MTKIs). A common characteristic of most of these drugs is that they are inhibitors of angiogenesis and also target additional receptors located on the surface of the cancer cell. Representative examples include the already approved and registered sunitinib and sorafenib, as well as AMG 706. Considering the observed development of tumor resistance to tyrosine kinase inhibitors and in order to circumvent drug-associated side effects, the discovery of new templates and their subsequent elaboration to clinically useful RTK inhibitors continues to be an important issue. Herein we report the discovery of a new class of cell-permeable RTK inhibitors belonging to the indeno ACHTUNGTRENNUNG[1,2-d]pyrido ACHTUNGTRENNUNG[1,2-a]pyrimidine-11,12dione class of compounds. Chemistry

The reaction of furazano[3,4-b]quinoxaline 1-oxide with cyclopentadiene: trapping of the 2,3-dinitrosoquinoxaline intermediate

The trapping of the 2,3-dinitrosoquinoxaline by reaction of furazano[3,4-b]quinoxaline 1-oxide with cyclopentadiene is reported

Synthesis of heterocyclic propellanes. Preparation and transannular reactions of 5-ethoxycarbonylmethylene-cyclooctanone and the corresponding oximes and hydrazones

Abstract 5-Ethoxycarbonylmethylene-cyclooctanone ( 3 ) is prepared by Wittig monoolefination of dione 1 with phosphorus ylide 2 . Thermal transannular cyclization of oxime 6 and phenylhydrazone 12 of the ketone 3 affords 3-oxa-2-aza- and 2,3-diaza[3.3.3] propellanes 7 and 14 respectively. Irradiation of ketone 3 , its oxime 9 , and its dimethylhydrazone 16 furnish 9-oxa-, and 9-aza[3.3.2] propellanes 11 , 10 , and 17 , respectively. In addition to the propellane 14 , phenylazobicyclo compound 13 is also obtained from phenylhydrazone 12 . The acetyl derivatives 8 and 15 of propellanes 7 and 14 are also prepared and studied.