Combined Theoretical and Experimental Investigations: Design, Synthesis, Characterization, and In Vitro Cytotoxic Activity Assessment of a Complex of a Novel Ureacellobiose Drug Carrier with the Anticancer Drug Carmustine.

Drug delivery systems (DDSs) are used to transport drugs which are characterized by some pharmaceutical problems to the specific target site, enhancing therapeutic efficacy and reducing off-target accumulation in the body. In this work, one of the recently synthesized molecules, 1,10-N,N'-bis-(ß-ᴅ-ureidocellobiosyl)-4,7,13,16-tetraoxa-1,10-diazacyclooctadecane (TN), was tested as a potential drug carrier towards the anticancer drug carmustine. For this purpose, different techniques were used, from synthesis and calculations to cytotoxicity assessment. Our results showed that TN is characterized by a very compact geometry, which significantly impacts its complexation properties. Although it forms a very stable complex with carmustine, it adopts a non-inclusion geometry, as verified by both experimental and theoretical NMR analyses. The cytotoxicity study performed for all analyzed molecules (TN; carmustine; TN:carmustine complex) towards normal and cancer (breast and colon) cells revealed that TN is not toxic and that the formation of complexes with carmustine reduces the toxicity of carmustine to normal cells.

Palladium(0)-catalysed synthesis of 2,3- and 3,4-unsaturated aryl ß-O-glycosides.

Arylation of 6-O-tert-butyldiphenylsilyl-3,4-di-O-isobutyloxycarbonyl-d-glucal (3) with various phenols in the presence of a catalytic amount of palladium(0) gave the corresponding 2,3- and 3,4-unsaturated ß-O-glycosides. The reaction is stereospecific, in all cases, only the ß-anomer is formed.

Synthesis of new saccharide azacrown cryptands.

New cryptands including bis-azacrown and saccharidic moieties in their structure were prepared in several steps by applying Staudinger-aza-Wittig reaction (SAW). Syntheses have been started from cheap, easily available commercial compounds such as D-glucose, D-cellobiose and D-lactose subsequently transformed into their derivatives in fairly good yields (60-65%) and suitable to give desired final cryptands by direct SAW coupling reactions.

New sugar-derived bifunctional chiral ureas as highly effective organocatalysts in asymmetric aza-Henry reaction.

A simple synthesis of series of new catalysts derived from chiral bifunctional ureas is described. The aza-Henry reaction of imines with nitromethane was promoted by sugar derived bifunctional organocatalysts to give optically active ß-nitroamines. The aza-Henry reaction products were obtained in good yields (35-98%) and ee up to 99%.

New ureas containing glycosyl and diphenylphosphinyl scaffolds: synthesis and the first attempts to use them in asymmetric synthesis.

Chiral ureas containing glycosyl and diphenylphosphinyl scaffolds were found to be an effective organocatalyst. They were synthesised in high yields by a one-pot tandem Staudinger/aza-Wittig coupling reaction. The first attempts of using them in asymmetric synthesis are presented. Yields of the Morita-Baylis-Hillman reaction were moderate with an enantiomeric excess of up to 80%.

Synthesis of bis-cellobiose and bis-glucose derivatives of azacrown macrocycles as hosts in complexes with acetylsalicylic acid and 4-acetamidophenol.

Two new C2 symmetric bis-cellobiose and bis-glucose azacrown derivatives were prepared according to the one-step procedure using azacrown ethers and azidosaccharides. Their complexes with aspirin and paracetamol were studied with the use of proton NMR spectroscopy. It was found that these pseudocryptands bind aspirin and paracetamol but each one in a different manner.