Band 17, Heft 3-4

A mimic of a plausible biosynthetic intermediate of bisho­mononactic acid, one of the monomers of macrotetrolide antibiotics (polynactin), was synthesized as a thiol ester. FAB-MS analysis showed that fermentation of polynactin producing Streptomyces griseus with the compound, afforded the unnatural polynactins containing bishomononactic acid(s).

A double regioselective deprotection of symmetrical tethered isopropylidenated monosaccharides has been elaborated. This mild and simple methodology involving iodine and acetonitrile, allows breaking of dioxolane and dioxane moieties and affords new chiral structures in good yields. Spectroscopic characterization of these molecules includes FTIR, ESI-MS, 1 H and 13 C NMR, and also 2D-COSY, HMQC and HMBC measurements.

In the present contribution we study the reaction of 4-hydroxy- and 4-chloro-2-methylquinolines with Vilsmeier-Haack reagent. The reaction of 2-(4-chloroquinolin-2-yl)-3-hydroxy­acrylaldehydes thus obtained with nucleophiles leads to potentially bioactive quinolines that contain pyrazole and piperidine groups.

Various quinoline carboxaldehydes were prepared from corresponding anilides using classical Vilsmeier-Haack reaction conditions and transformed into their Baylis-Hillman adducts. The synthesized Baylis-Hillman adducts were screened for their in vitro antimalarial activity against Plasmodium falciparum . Most of the compounds out of 21 compounds synthesized and screened exhibited substantial antimalarial activity.

A green three-component one pot condensation synthesis of 16 indenoquinolinone from aromatic aldehydes, 1-aminonaphthalene or 1-aminoanthracene and 1,3-indanedione catalyzed by Fe(OTf) 3 is described. The isolated yields ranged from 80% to 92%.

A base-catalyzed, one-pot and facile method for the synthesis of 2-amino-4,5-dihydro-4-arylpyrano[3,2- b ]indole-3-carbonitriles is reported. This procedure includes a novel three-component reaction of indolin-3-one with aromatic aldehydes and malononitrile in ethanol in the presence of ammonium acetate as the catalyst.

The reaction of 4-amino-2-benzyl-1-methyl-5-ethoxycarbonylpyrimidinium iodide ( 3 ) with alcoholic methylamine resulted in the formation of the methylimine of 2-amino-4-hydroxy-6-methylamino-5-phenylpyridine-3-carbaldehyde ( 5 ). Heating of the same pyrimidinium salt in benzylamine gave a mixture of products of two C–C recyclizations: 2-benzyl-4-benzylamino-5-carbamoylpyrimidine ( 7 ) and the benzylimine of 4-amino-2-benzyl-6-benzylaminopyrimidine-5-carbaldehyde ( 8 ). The reaction of 2-amino-1,4-dimethyl-5-ethoxycarbonylpyrimidinium iodide ( 10 ) with KOH ethanolic solution gave a single product of C–C-recyclization: 2-amino-5-acetyl-4-hydroxypyrimidine ( 11 ).

The synthesis of new sulfur-linked di- and triheterocyclic compounds containing thienotriazolopyrimdine and triazolothiadiazole systems with promising biological activity is described.

Syntheses of 5-amino-3-aryl- and 3-amino-5-aryl-1 H -pyrazoles from β-bromo-α-(ethylsulfanyl)cinnamonitrile are described. The β-bromo-α-(ethylsulfanyl)cinnamonitriles were oxidized with H 2 O 2 to the corresponding β-bromo-α-(ethylsulfinyl)cinnamonitriles. Subsequent treatment of the resulting sulfoxides with hydrazine hydrate or methylhydrazine followed by hydrochloric acid hydrolysis afforded 5-amino-3-aryl- and 3-amino-5-aryl-1 H -pyrazoles, respectively, in good yields.

Condensation of thiosemicarbazones 2 derived from 1-tetralones ( 1 ) with chloroacetic acid in presence of N -methylpyridinium tosylate (an ionic liquid) yields 2-substituted-4-thiazolidinones 3 . The reaction of 2 with α-halo carbonyl compounds at room temperature under grinding conditions yields 2,4-disubstituted thiazoles 4 in excellent yields. The structures of compounds 2–4 have been esta­b­lished on the basis of elemental analysis, IR, NMR and mass spectral data.

Cyclocondensation of 2-[bis(methylthio)methylene]malononitrile and 2-amino-benzenthiol afforded 2-(benzo[ d ]thiazol-2-yl)malononitrile. This compound, on treatment with phosphorus pentasulfide, gave the corresponding thioamide derivative in a regioselective manner. Reaction of this compound with several α-bromocarbonyl compounds gave new 2-[( E )-(benzo[ d ]thiazol-2(3 H )-ylidene)(cyano)methyl]thiazoles.

2-(4,5-Dihydro-4-oxothiazol-2-yl)acetonitrile ( 1 ) was reacted with acetophenone ( 2 ) to give 2-(4,5-dihydro-4-oxothiazol-2-yl)-3-phenylbut-2-enenitrile ( 3 ). The reactivity of product 3 towards aromatic aldehydes 4a–d , cyanomethylene reagents 6a,b , aryl diazonium salts 10a–d , phenylisothiocyanate and elemental sulfur was studied. Some of the newly synthesized compounds were used to synthesize fused derivatives. The anti-tumor evaluation of selected compounds against three cancer cells namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) showed that some of them have a high inhibitory effect and compound 19 was found to be more active than the standard on NCI-H460 and SF-268.

Spiro indane-1,3-dione pyrrolizidine compounds were synthesized by the 1,3-dipolar cyclo-addition reaction of ninhydrin, L-proline and two kinds of alkene (chalcone and ( E )- β -aryl-nitrostyrene). All these reactions proceeded with good yield and with high regio- and stereoselectivity. It was found that the use of two kinds of alkene lead to different regioselectivity. In the structure of D1 and D2 , the electron-withdrawing group (EWG; benzoyl group) is attached to C-3 and the phenyl group is at C-4 of the newly constructed pyrrolidine. In the structure of D3-D7 , the EWG (nitro group) is at C-4 and the phenyl group is at C-3 of the newly constructed pyrrolidine.