Dušan Lazar

Catalytic Preparation and Characterization of C60Br24

Abstract In this paper the procedure for catalytical bromination of C60 with elementary bromine with FeBr3 as a catalyst is described. In this procedures only one reaction product - C60 Br24 is obtained. The twenty four bromine atoms are symmetrically distributed over the C60 sphere, which was confirmed by thermogravimetric analysis. The yield of bromine derivative in this reaction is 98%.

Synthesis, X-ray crystal structures and biological activity of 16-amino-17-substituted-D-homo steroid derivatives.

D-Homo derivatives in the androstane and estrane series, 12-19, were synthesized by a fragmentation-cyclization reaction of 16-oximino-17-hydroxy-17-substituted derivatives 3-9, or by cyclization of the corresponding D-seco derivatives 20-26. The structures were confirmed by X-ray analysis of compounds 12 and 16. Preliminary assessment of inhibitory effects of D-homo derivatives from androstane series towards aromatase, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase/C17-20 lyase (P450c17) and 17 beta-HSD indicated much lower inhibitory potential compared to previously tested activity of another type of D-modified steroids, namely D-seco derivatives. Also, assessment of potential antiestrogenic activity of derivatives from estrane series showed absence of such an activity.

Synthesis, structure, and screening of estrogenic and antiestrogenic activity of new 3,17-substituted-16,17-seco-estratriene derivatives.

The starting compound for synthesis of new 16,17-seco-estratriene derivatives was 3-benzyloxy-17-hydroxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile (1b), obtained from estrone in several synthetic steps. 17-Tosyl, -chloro-, bromo-, and -iodo- derivatives 2b, 4b, 5b, and 6b were prepared directly from secocyanoalcohol 1b, while the 17-fluoro-derivative 3b was obtained from tosylate 2b in the reaction with tetrabutyl ammonium fluoride. The corresponding 3-hydroxy derivatives of these compounds were produced by action of hydrogen in presence of Pd/C, except the 3-hydroxy-17-iodo derivative 6a, which was obtained from 3-hydroxy-17-tosyloxy derivative 2a. All the newly synthesized compounds in biological tests on experimental animals exhibited an almost total loss of estrogenic activity, while most of them even prevented the action of endogenous estrogens. On the other hand, most of them, except compounds 3a and 6b, partially hindered the action of estradiol benzoate, behaving as moderate antagonists.

A novel rearrangement of steroidal α-hydroxy oximes

Abstract By the action of acidic titanium trichloride upon 16-oximino-17α-benzyl-17β-hydroxy derivatives in the androstane and estrane series the 16-oxo-17β-benzyl-17α-hydroxy derivatives 6 and 7 with inversed configuration at C 17 were obtained. A mechanism for this novel rearrangement is proposed.

A novel fragmentation-cyclization reaction of steroidal α-hydroxy oximes

Abstract By a novel “one pot” fragmentation-cyclization reaction 17β-hydroxy-17α-substituted-16-oximino derivatives in the androstane and estrane series were converted to a new type of D-homo derivative.

17β-Hydroxy-3-methoxyestra-1,3,5(10)-triene-6,7-dione 7-Oxime

X-ray structure analysis of the title compound, C 19 H 23 NO 4 , showed an unexpected anti orientation for the 6-oxo-7-oximino function. After molecular-mechanics calculations, the H atom of the 17-hydroxy moiety, which participates in a strong hydrogen bond formed in the crystalline state, changed its orientation substantially. Some change in the conformation of ring B was also observed.

Green upconversion in Y2O3:Yb nanopowder

Abstract. Green emission lines, in addition to the blue and the red, were observed upon 980 nm excitation in yttrium oxide (Y2O3) nanopowder codoped with Yb3+ and Tm3+, synthesized by the chemical combustion method. Upconversion emission studies suggest that the number and characteristics of the green lines are influenced by the annealing temperature as well as by the Yb3+/Tm3+ concentration ratio, opening possibilities for new customized applications. The chromaticity properties of the upconversion spectra were quantified by the Commission Internationale de l’éclairage coordinate analysis.

D-Secoestrone Derivatives. Part 5. 3-Methoxy-17-oxo-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile and 17-Hydroxy-3-methoxy-17-phenyl-16,17-secoestra-1,3,5 (10)-triene-16-nitrile.

The two title 16,17-secoestrone derivatives, 3-methoxy-17-oxo-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile, C(25)H(27)NO(2), (I) (17-oxo substituent), and 17-hydroxy-3-methoxy-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile, C(25)H(29)NO(2), (II) (17-hydroxy substituent), have quite different conformations in the solid state. These conformational differences can be minimized by molecular mechanics calculations. Thus, the remarkable difference in the biological activity of the two compounds, e.g. the strong oestrogenic characteristics of (I) and the moderate antioestrogenic action of (II), must be caused by the difference in substitution at C17. In (II), the molecules are linked by O-H...N hydrogen bonds, forming spirals along the b direction.

D-Secoestrone derivatives. VII. 3-Methoxy-17-keto-17-benzyl-16,17-secoestra-1,3,5(10)-trien-16-nitrile and (17S) 3-methoxy-17-hydroxy-17-benzyl-16,17-secoestra-1,3,5(10)-trien-16-nitrile

The two title compounds 3-methoxy-17-keto-17-benzyl-16,17-secoestra-1,3,5(10)-trien-16-nitrile, C26H29NO2, (I) and (17S)-3-methoxy-17-hydroxy-17-benzyl-16,17-secoestra-1,3,5(10)-trien-16-nitrile, C26H31NO2, (II), have similar conformations in the solid state. The models from molecular mechanics calculations show an improvement in the similarity of the calculated (modeled) structures. However, they also revealed that the global energy minimum structure of (I) is a structure with a rotated 17-benzyl moiety. Thus, the difference in the bio logical activity of the two compounds ((I) a moderate anti-oestrogen, (II) biologically inactive) must be primarily caused by the difference in the orientation of the 17-benzyl moiety in the free molecules. In (II), the molecules are linked by weak O—H…N hydrogen bonds, forming spirals along the b direction.

Hydrogen bonding and structure-activity analysis of some antiandrogens

Androgen hormones, the group of steroid hormones, are mailsex hormones. They are vital to numerous physiologicalprocesses including development of mail sex organs andsecondary mail sex characteristics. Beside their normal physi-ologicalfunctions,androgenscanberesponsibleforgrowthandmultiply of malignant cells, or can be cause of some otherdiseases (benign prostate gland hiperthense (BPH), prostategland cancer, brain cancer, breast cancer, acnes, etc.). The factthat the androgens play the key role in many human diseasescauses the intensive investigations in the field of obtaining andapplying antiandrogens. Antiandrogens are substances whichblockade the biological activities of androgens, and because ofthattheyareusedintherapyofsomeandrogen-dependdiseases.In our study of some androstene and adrostane derivatives withpotentional antiandrogenic properties a number of androgeniccompounds were synthesized, structurally analysed and testedfor biologic effects. In this paper our attention was directedtoward the examination of their hydrogen bonding character-istics. Examination of the structures of compounds having highaffinityforandrogenreceptorsledtothesuggestionthatsteroid-receptor binding is primarily the result of interactions betweenthe receptor and the steroidal D ring. Especially, of the greatimportance for the receptor binding are the position and thepossible hydrogen bonds of H-atom from 17β-hydroxyl group.Activity of androgens might be controlled by the A ring and3-oxo or 3-hydroxyl group. As a part of our study, the influ-ences of molecule flexibility and substituents on the structure-activity relationship were also examined. The crystal struc-tures of the compounds were determined by the single crystalX-ray diffraction methods. The energy minimum structureswere obtained by molecular-mechanics calculations.