Virág Zsoldos-Mády

Synthesis, Structure, and in vitro Antitumor Activity of Some Glycoside Derivatives of Ferrocenyl-Chalcones and Ferrocenyl-Pyrazolines†

Some new glycosides of 3‐ferrocenyl‐1‐(4′‐hydroxyphenyl)‐prop‐2‐en‐1‐one were prepared and transformed into the corresponding pyrazoline and pyrazole derivatives. Using methyl‐hydrazine, formation of regioisomers was observed. DDQ was found to be a mild and efficient reagent for the pyrazoline‐pyrazole dehydroaromatization process. The structure of the new compounds was proved by IR and NMR spectroscopy. The in vitro antitumor activity of the substances was investigated against human leukemia (HL‐60) cells by the MTT method. Among these new compounds some chalcone derivatives (3 a, 3 b, 5 a, and 5 b) showed attractive in vitro antitumor effects on human leukemia cells. These molecules contained ferrocenyl moieties and a p‐hydroxy‐phenolic ring or a size‐independent apolar substitution of that.

A new approach to 6-deoxy-D-allofuranose- and 6-deoxy-L-talofuranose derivatives from 1,2:5,6-di-O-isopropylidene α-D-glucofuranose

Abstract3-O-Acetyl-1,2-O-isopropylidene-α-D-allofuranose (2 b) was prepared from 1,2:5,6-di-O-isopropylidene-α-D-allofuranose (1 b). Treatment of2 b with triphenylphosphine-diethyl azodicarboxylate afforded regio- and stereospecifically the 5,6-epoxy-α-D-allo derivative (3). The other diastereomeric compound, 5,6-epoxy-1,2-O-isopropylidene-β-L-talofuranose (6) was also prepared stereoselectively from2 bvia the intermediates5 a and5 b. The epoxy sugars3 and6 were converted with lithium aluminum hydride to the corresponding 6-deoxy-1,2-O-isopropylidene-α-D-allofuranose (4 a) and -β-L-talofuranose (7 a) derivatives. Hydrolysis of4 a and7 a afforded 6-deoxy-D-allose and 6-deoxy-L-talose, respectively. The corresponding 3,5-di-O-acetyl- (4 b and7 b) and the 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) derivatives (4 c and7 c) are also described. Selective removal of the isopropylidene group and subsequent acetylation offers a convenient route to prepare sugar derivatives containing furanose ring, like8 b, as a suitable precursor for nucleoside analogs.Zusammenfassung1,2:5,6-Di-O-isopropyliden-α-D-allofuranose (1 b) wird zunächst in das 3-O-Acetyl-1,2-O-isopropylidenderivat2 b übergeführt, aus welchem beim Umsatz mit Hilfe von Triphenylphosphin-Azodicarbonsäureester das 5,6-Epoxy-α-D-allozuckerderivat3 regio- und stereospezifisch entsteht. Das andere diastereomere Derivat, die 5,6-Epoxy-1,2-OL-isopropyliden-β-L-talofuranose (6) wurde auch aus2 b über die Zwischenprodukte5 a und5 b stereoselektiv hergestellt. Die Epoxyzucker3 und6 wurden mit LiAlH4 in die entsprechenden 6-Desoxy-1,2-O-isopropyliden-α-D-allofuranose (4a) bzw. -β-L-talofuranose (7 a) umgewandelt. Hydrolyse von4 a und7 a ergab 6-Deoxy-D-allose bzw. 6-Desoxy-L-talose. Die entsprechenden 3,5-Di-O-acetyl- (4 b und7 b) und 3,5-O-(Tetraisopropyldisiloxan-1,3-diyl)-derivate (4 c und7 c) werden ebenfalls beschrieben. Verbindung4 c konnte in das 1 β,2-Di-O-acetylderivat (8 b) umgewandelt werden, welches unmittelbar für Nucleozidsynthesen eingesetzt werden kann.

2-Acetamido-2-deoxyaldonolactones from sugar formazans

Abstract A new approach towards simple aldonic acid derivatives starting from the corresponding aldoses via the 2-acetamido-2-deoxy formazans resulted in the synthesis of 2-acetamido-2-deoxy- d -galactono-1,4-lactone (8), and its 6-deoxy (11) and 6-azido-6-deoxy (14) analogues on treatment with trifluoroacetic acid. The five-membered ring structure of the lactones and that of the intermediate lactone phenylhydrazone (7) was proved by 1H and 13C NMR studies, including deuterium-induced differential isotope shift (DIS) measurements. With sodium borohydride, lactones 8 and 11 were converted into 2-acetamido-2-deoxy- d -galactitol (15) and its 6-deoxy analogue (17), respectively.

Studies on the N-acetyl-β-d-hexosaminidase B from germinating Lupinus luteus L. seeds II. Mechanism and inhibition with some 2-acetamido-2-deoxyaldono(1 å 4)lactones

The N-acetyl-beta-D-hexosaminidase B of germinating yellow lupin seeds catalyzed the hydrolysis of both p-nitrophenyl-N-acetyl-beta-D-glucosaminide and -galactosaminide substrates. The investigation of the pH dependence of the kinetic parameters (Vmax and Vmax/Km) demonstrated that two common ionizable groups (probably two carboxyl groups) play an essential role in the catalysis. That is, the enzyme has a lysozyme-like splitting mechanism, and the possibility of an anchimeric assistance provided by the acetamido group seems to be negligible. The presence of a deprotonated carboxyl group near the glycosidic linkage was also supported by inhibition with 1-thio substrate analogues. On the other hand, some 2-acetamido-2-deoxyaldono(1----4)lactones proved to be effective inhibitors of the hexosaminidase with the exception of the D-arabinose derivative, which can be explained by high stereospecificity in the binding.

NEW EVIDENCE FOR ISOMERISM OF THE FORMAZYL GROUP. SYNTHESIS OF SELECTIVELY PROTECTED 2-DEOXY-GALACTOSE FORMAZANS

A new application of the formazyl activation provided selectively protected new derivatives of both 2-deoxy-D-galactose and 2-acetamido-2-deoxy-D-galactose formazans from 6-amino-6-deoxy-D-galactose 6,4-cyclic carbamate (1) under very simple conditions. The 1H NMR spectrum of the acetylated 2-deoxy derivative 7 revealed an equilibrium between chelated and unusual non-chelated forms of the formazan moiety in solution.

New Carbohydrate Derivatives of Norfloxacin

New classes of sugar derivatives of the antibacterial drug norfloxacin (1) were synthesized by substituting the N‐4′ of the piperazinyl moiety of the molecule. Direct coupling with gluco‐ and galactopyranosyl units afforded glycosylamines 2–5. Introduction of urea or thiourea linkage between glycosyl and norfloxacin units was produced with the corresponding glycosyl isocyanates or isothiocyanates. For the synthesis of unprotected sugar urea compounds, a new approach was applied by using 1,2‐N, O‐carbonyl‐β‐D‐glycopyranoses. Hydrazinocarbonyl‐methyl‐ and ‐propyl spacers also were found appropriate for linking norfloxacin with sugar units. Dedicated to Professor A. Messmer on the occasion of his 80th anniversary.

Transformation of aldose formazans. Novel synthesis of 2-acetamido-2- deoxypentonolactones and a new pent-2-enose formazan

2-Acetamido-2-deoxypentonolactones were synthesized from per-O-acetylated formazans of D-ribose, D- and L-arabinose, respectively. In dimethyl sulfoxide, a novel spontaneous transformation of the per-O-acetyl-pentose formazans into new 3,4,5-tri-O-acetyl-pent-2-enose formazans has been recognized. Additional examples for the occurrence of the isomerism between pseudo-aromatic chelate and open phenylazo-phenylhydrazone system were demonstrated by (1)H NMR spectroscopy in both the unprotected pentose formazans and 3,4,5-tri-O-acetyl-pent-2-enose formazans. Computational calculations supported higher stability of the ring form.