Janoš Čanadi | University of Novi Sad, Faculty of Sciences (original) (raw)

Papers by Janoš Čanadi

Research paper thumbnail of Substituent efects on the carbon-13 chemical shifts in α-phenylpyridylacrylic acids

Journal of Molecular Structure, 1992

Abstract The 13 C N.M.R. spectra of some substituted α-phenylpyridylacrylic acids, α-phenyl, α-(3... more Abstract The 13 C N.M.R. spectra of some substituted α-phenylpyridylacrylic acids, α-phenyl, α-(3-pyrydyl) and α-(3-pyrydyl-N-oxide) cinnamic acids were determined in deuterated dimethyl sulfoxide (d 6 -DMSO). It has been shown that the subsitutent chemical shifts (SCS) for C β atom ethylenic bond of the examined compounds correlated linearely with the summ of the corresponding substituent constants in the both rings (σ x + σ Y ). This correlation was interpreted as evidence that the electronic effects of both substituents are involved in conjugated aromatic system.

Research paper thumbnail of Effect of substituents on the 13C NMR chemical shifts of para-substituted α-phenyl-β-pyridylacrylic acids

Journal of Molecular Structure, 1997

The 13C NMR spectra of para-substituted α-phenylcinnamic and 3- and 4-pyridylacrylic acids, with ... more The 13C NMR spectra of para-substituted α-phenylcinnamic and 3- and 4-pyridylacrylic acids, with a wide range of substituents effects, were determined in deuterated dimethylsulfoxide (DMSO-d6). The effect of substituents in both the α-phenyl and β-pyridine groups in these acids is investigated using linear free energy relationships and multiple regression analysis as applied to 13C NMR chemical shifts of the Cα

Research paper thumbnail of Nucleophilic opening of the 3,5-anhydro ring in 1,2-O-cyclohexylidene- -D-xylofuranose

Journal of the Serbian Chemical Society, 2001

The reactivity of the oxetane ring in 3,5-anhydro-1,2-O-cyclohexylidene- -D-xylofuranose (1) was ... more The reactivity of the oxetane ring in 3,5-anhydro-1,2-O-cyclohexylidene- -D-xylofuranose (1) was exemplified by its regiospecific nucleophilic opening. The action of concentrated hydrobromic or hydroiodic acid on 1 resulted in the exclusive formation of the 5-deoxy-5-halo derivatives, while the action of acetyl chloride or acetyl bromide yielded the corresponding 3-O-acetyl-5-deoxy-5-halo derivatives in 70 - 90 % yield. Under strongly acidic reaction conditions, the protection of the cyclohexylidene acetal function remained intact.

Research paper thumbnail of An Improved Synthesis for Obtaining 2-Deoxy-2-iodo-D-mannopyranose Derivatives

Journal of the Serbian Chemical Society

Research paper thumbnail of The Effect of Hydroxyl Moieties and Their Oxosubstitution on Bile Acid Association Studied in Floating Monolayers

The Scientific World Journal, 2014

Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-... more Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-solubilizing ability. However, the toxicity of bile salts increases with improving fat-solubilizing capability and so an optimal combination of efficient solubilization and low toxicity is necessary. To improve hydrophilicity (and decrease toxicity), we substituted hydroxyl groups of several natural bile acid (BA) molecules for oxogroups and studied their intrinsic molecular association behavior. Here we present the comparative Langmuir trough study of the two-dimensional (2D) association behavior of eight natural BAs and four oxoderivatives (traditionally called keto-derivatives) floated on an aqueous subphase. The series of BAs and derivatives showed systematic changes in the shape of the compression isotherms. Two types of association could be distinguished: the first transition was assigned to the formation of dimers through H-bonding and the second to the hydrophobic aggregation of ...

Research paper thumbnail of Selective antitumour activity and ERα molecular docking studies of newly synthesizedd-homo fused steroidal tetrazoles

Research paper thumbnail of Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives

European Journal of Medicinal Chemistry, 2012

New 17-picolyl and 17-picolinylidene androstane derivatives, 3e10, 15, 18, 19, 22 and 23, were sy... more New 17-picolyl and 17-picolinylidene androstane derivatives, 3e10, 15, 18, 19, 22 and 23, were synthesized starting from 17a-picolyl-androst-5-en-3b,17b-diol (1) and 17(Z)-picolinylidene-androst-5-en-3b-ol (2). Reaction of 1 with m-chloroperoxybenzoic acid gives 5a,6a-epoxy N-oxide derivative 3, or, with Jones reagent, 3,6-dione derivative 4; while 17a-picolyl-androst-5-en-3b,4a,17b-triol (5) or 3b,4b,17b-triol (6) derivatives are obtainable from 1 using SeO 2 in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10. Oppenauer oxidation of 1 and 2 yields 4-en-3-one derivatives 11 and 12, which, with H 2 O 2 in 4 M NaOH, affords 4a,5a and 4b,5b-epoxides 13, 14, 16 and 17. New 4-methoxy-3-keto derivatives 15 and 18 were obtained from 13 and 14, or, with methanol in 4 M NaOH, from 16 and 17. Reduction of 11 with NaBH 4 gives 22, which was then acetylated to obtain 23. All new derivatives were screened for antitumor activity against human breast adenocarcinoma ERþ, MCF-7; human breast adenocarcinoma ER-, MDA-MB-231; prostate cancer AR-, PC-3; human cervix carcinoma, HeLa; and colon cancer, HT-29 cells; as well as one human non-tumor cell line, MRC-5. Compounds 3, 5, 6, 8, 10, 18, 19 and 22 exhibited significant antitumor activity against MDA-MB-231 breast cancer cells; while 5, 6 and 10 also showed strong cytotoxicity against HT-29. Only compound 19 exhibited significant activity against MCF-7 breast cancer cells. No compounds displayed cytotoxicity against non-tumor MRC-5 cells.

Research paper thumbnail of Synthesis and Biological Activity of Some 17a-Substituted Homolactones of Androst-5-ene Derivatives

Collection of Czechoslovak Chemical Communications, 2005

Some new 17a-homolactones were prepared from 3β-hydroxy-16-(hydroxyimino)androst-5-en-17-one (1) ... more Some new 17a-homolactones were prepared from 3β-hydroxy-16-(hydroxyimino)androst-5-en-17-one (1) as a starting compound, which was transformed first to the corresponding 17α-phenyl and 17α-benzyl derivatives 2 and 3. The structure of compound 3 was confirmed by X-ray structure analysis. Beckmann fragmentation of compounds 2 and 3 yielded 16,17-seco-cyano ketones 4-7, whose reduction with NaBH4 gave 16,17-seco-cyano alcohols 8-11, whereby the structure of compound 7 was established by X-ray structural analysis. Compounds 8-11 served as the starting compounds for obtaining lactones 12 and 13 in a reaction with potassium hydroxide in ethylene glycol. One-pot procedures were also developed for preparing 17a-homolactones 12, 13 and 16 from the hydroxyimino alcohols 2, 3 and 14. Compounds 12 and 13 showed an inhibitory activity against the enzyme aromatase (63 and 59%, respectively).

Research paper thumbnail of An intramolecular one-pot synthesis of steroidal triazoles via 1,3-dipolar cycloadditions of in situ generated diazo compounds

Tetrahedron Letters, 2009

A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular... more A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular 1,3-dipolar cycloaddition of a steroidal 16,17-seco-17-diazo-16-nitrile system. The structures of the products are established by X-ray and NMR studies. The in vitro antiproliferative activity of the steroidal triazoles against three tumor cell lines was evaluated.

Research paper thumbnail of New D-modified androstane derivatives as aromatase inhibitors

Steroids, 2001

Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy... more Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy-17-substituted derivatives 2–4 gave by the Beckmann fragmentation reaction the corresponding D-seco derivatives 6–9. Besides, in the case of the 17-hydroxy-17-methyl-16-oximino derivative 2, as a result of the rearrangement, the hydrolysis product 5 of the 16-oximino group with the opposite configuration at the C-17 was obtained. By the Oppenauer oxidation and/or

Research paper thumbnail of 17-Picolinylidene-androst-5-ene derivatives and their antiaromatase and cytotoxic activity

Arkivoc, 2010

Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were syn... more Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were synthesized. By oxidation of 3β-hydroxy derivative 2 with Jones reagent the corresponding 17(Z)-picolinylidene-androst-4-ene-3,6-dione 4 was obtained. The Oppenauer oxidation of 2 yielded 4-en-3-one derivative 3, which reacted with potassium-t-butoxide in t-butanol to give 4ene-3,6-dione 4 and 4-hydroxy-4,6-dien-3-one 5 derivatives. Nitration of compound 1 afforded 6-nitro-5-ene derivative 6. The reaction of compound 3 with NaBH 4 in ethanol afforded stereoselectively the 3β-hydroxy-4-ene derivative 7, the acetylation of which gave 3β-acetoxy derivative 8 whereas 17-picolinylidene derivatives 9-14 have been synthesized earlier. Compounds 4-8 were tested on potential inhibitory activity against the enzyme aromatase. Satisfactory inhibitory activity showed compounds 4, 5, 7 and 8. Cytotoxicity in vitro against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231 and prostate cancer AR-, PC-3) and normal fetal lung fibroblasts, MRC-5, of compounds 1-14 was also evaluated. Strong cytotoxic activity showed compound 5 against MDA-MB-231 (IC 50 9.3 µM) and compound 7 against PC-3 (IC 50 10.1 µM). All compounds were not toxic to healthy MRC-5 cells.

Research paper thumbnail of Synthesis and biological evaluation of some new A,B-ring modified steroidal d-lactones

Steroids, 2008

Starting from the d-homo lactones of androst-4-en-3-one 3 and 4, prepared from 1 and 2, the new 1... more Starting from the d-homo lactones of androst-4-en-3-one 3 and 4, prepared from 1 and 2, the new 17a homolactones 5–12, 14 and 15, were synthesized. The 4-hydroxy compounds 9 and 10 were obtained through the reaction of 4α, 5α-(5 and 7) and 4β, 5β-(6 and 8) ...

Research paper thumbnail of Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acids on verapamil hydrochloride in biophysical-chemical model experiments

Journal of the Serbian Chemical Society, 2011

Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acid... more Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acids on verapamil hydrochloride in biophysical-chemical model experiments

Research paper thumbnail of Stereospecific synthesis of (−)- allo-muscarine from d-glucose

Carbohydrate Research, 1996

ABSTRACT The key chiral synthon in a novel synthesis of (-)- allo -muscarine from D-glucose has b... more ABSTRACT The key chiral synthon in a novel synthesis of (-)- allo -muscarine from D-glucose has been prepared by three independent routes. The most efficient one includes a four-step conversion via the 4- O -benzoyl derivatives of starting 2,5-anhydro-3,5-di- O -methanesulfonyl-L-idose ethylene acetal ( 2a ) into 2,5-anhydro-3,6-dideoxy-L- lyxo- hexose ethylene acetal ( 4b ). The intermediate 4b was efficiently converted into the chiral synthon 2,5-anhydro-4- O -benzoyl-3,6-dideoxy-L- arabino -hexose ( 4c ) by Mitsunobu reaction.

Research paper thumbnail of 17-Picolinylidene-substituted steroid derivatives and their antiaromatase and cytotoxic activity

ARKIVOC, 2009

Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were syn... more Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were synthesized. By oxidation of 3β-hydroxy derivative 2 with Jones reagent the corresponding 17(Z)-picolinylidene-androst-4-ene-3,6-dione 4 was obtained. The Oppenauer oxidation of 2 yielded 4-en-3-one derivative 3, which reacted with potassium-t-butoxide in t-butanol to give 4ene-3,6-dione 4 and 4-hydroxy-4,6-dien-3-one 5 derivatives. Nitration of compound 1 afforded 6-nitro-5-ene derivative 6. The reaction of compound 3 with NaBH 4 in ethanol afforded stereoselectively the 3β-hydroxy-4-ene derivative 7, the acetylation of which gave 3β-acetoxy derivative 8 whereas 17-picolinylidene derivatives 9-14 have been synthesized earlier. Compounds 4-8 were tested on potential inhibitory activity against the enzyme aromatase. Satisfactory inhibitory activity showed compounds 4, 5, 7 and 8. Cytotoxicity in vitro against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231 and prostate cancer AR-, PC-3) and normal fetal lung fibroblasts, MRC-5, of compounds 1-14 was also evaluated. Strong cytotoxic activity showed compound 5 against MDA-MB-231 (IC 50 9.3 µM) and compound 7 against PC-3 (IC 50 10.1 µM). All compounds were not toxic to healthy MRC-5 cells.

Research paper thumbnail of A novel route to 2-deoxy-2-iodo-d-mannopyranose derivatives

Carbohydrate Research, 1992

1,5-Anhydro-2-deoxy-D-hex-1-enitols are versatile synthons'*2. Various functional groups, such as... more 1,5-Anhydro-2-deoxy-D-hex-1-enitols are versatile synthons'*2. Various functional groups, such as chloro3, fluoro4-7, bromo8, or iodo'-I', may be introduced at position 2 by either direct or indirect addition of suitable agents across the double bond. Iodination of o-glucal triacetate, using iodine and silver benzoate in dry ben-zene9*10, iodine and silver acetate in methanol', N-iodosuccinimide in dry methanol'*, or iodonium bis(2,4,6-trimethylpyridine)perchlorate12, have been described, corresponding to the formal addition of alkyl or acyl hypoiodite across the double bond. However, the formation of free 2-deoxy-2-iodo sugars has not been described hitherto. We now report a formal electrophilic addition of "hypoiodous acid" to 3,4,6-tri-0-acetyl-o-glucal'3 (1) and 3,4-di-0-acetyl-6-0-tosyl-D-glucal'4 (2). Depending on the buffer system used and the pH, a mixture of the 2-deoxy-2-iodo esters 3 of 5 together with the corresponding 2-deoxy-2-iodo sugars 4 or 6, or only 4 or 6, were obtained. The compounds obtained could be used for the preparation of 2-deoxy sugars or Brigl's anhydrides. Thus, treatment of 1 or 2 with iodine in tert-butyl alcohol in the presence of acetate buffer (pH 5, room temperature, 3 h) gave a mixture of the 2-deoxy-2iodo-manno-esters 3 or 5 together with the corresponding Zdeoxy-Ziodo-a-o-mannopyranose derivatives 4 or 6, in the ratio 3 : 1. However, when this reaction was carried out in the presence of a phosphate or carbonate buffer (pH 6-7, room temperature, 3 h), the 2-deoq&iodo-aD -mannopyranose derivatives 4 or 6 were the only isolable products (50-60%). The structures of 3-6 were confirmed by the NMR data (Table I> and [cu], values. The above procedure for the preparation of the 2-deoxy-2-iodo-cuD -manno

Research paper thumbnail of Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright

Research paper thumbnail of The effect of hydroxyl moieties and their oxo-substitution on bile acid association studied in floating monolayers

Research paper thumbnail of An alternative synthesis of (+)- epiallo-muscarine from d-glucose

Carbohydrate Research, 1995

Research paper thumbnail of An intramolecular one-pot synthesis of steroidal triazoles via 1,3-dipolar cycloadditions of in situ generated diazo compounds

Tetrahedron Letters, 2009

A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular... more A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular 1,3-dipolar cycloaddition of a steroidal 16,17-seco-17-diazo-16-nitrile system. The structures of the products are established by X-ray and NMR studies. The in vitro antiproliferative activity of the steroidal triazoles against three tumor cell lines was evaluated.

Research paper thumbnail of Substituent efects on the carbon-13 chemical shifts in α-phenylpyridylacrylic acids

Journal of Molecular Structure, 1992

Abstract The 13 C N.M.R. spectra of some substituted α-phenylpyridylacrylic acids, α-phenyl, α-(3... more Abstract The 13 C N.M.R. spectra of some substituted α-phenylpyridylacrylic acids, α-phenyl, α-(3-pyrydyl) and α-(3-pyrydyl-N-oxide) cinnamic acids were determined in deuterated dimethyl sulfoxide (d 6 -DMSO). It has been shown that the subsitutent chemical shifts (SCS) for C β atom ethylenic bond of the examined compounds correlated linearely with the summ of the corresponding substituent constants in the both rings (σ x + σ Y ). This correlation was interpreted as evidence that the electronic effects of both substituents are involved in conjugated aromatic system.

Research paper thumbnail of Effect of substituents on the 13C NMR chemical shifts of para-substituted α-phenyl-β-pyridylacrylic acids

Journal of Molecular Structure, 1997

The 13C NMR spectra of para-substituted α-phenylcinnamic and 3- and 4-pyridylacrylic acids, with ... more The 13C NMR spectra of para-substituted α-phenylcinnamic and 3- and 4-pyridylacrylic acids, with a wide range of substituents effects, were determined in deuterated dimethylsulfoxide (DMSO-d6). The effect of substituents in both the α-phenyl and β-pyridine groups in these acids is investigated using linear free energy relationships and multiple regression analysis as applied to 13C NMR chemical shifts of the Cα

Research paper thumbnail of Nucleophilic opening of the 3,5-anhydro ring in 1,2-O-cyclohexylidene- -D-xylofuranose

Journal of the Serbian Chemical Society, 2001

The reactivity of the oxetane ring in 3,5-anhydro-1,2-O-cyclohexylidene- -D-xylofuranose (1) was ... more The reactivity of the oxetane ring in 3,5-anhydro-1,2-O-cyclohexylidene- -D-xylofuranose (1) was exemplified by its regiospecific nucleophilic opening. The action of concentrated hydrobromic or hydroiodic acid on 1 resulted in the exclusive formation of the 5-deoxy-5-halo derivatives, while the action of acetyl chloride or acetyl bromide yielded the corresponding 3-O-acetyl-5-deoxy-5-halo derivatives in 70 - 90 % yield. Under strongly acidic reaction conditions, the protection of the cyclohexylidene acetal function remained intact.

Research paper thumbnail of An Improved Synthesis for Obtaining 2-Deoxy-2-iodo-D-mannopyranose Derivatives

Journal of the Serbian Chemical Society

Research paper thumbnail of The Effect of Hydroxyl Moieties and Their Oxosubstitution on Bile Acid Association Studied in Floating Monolayers

The Scientific World Journal, 2014

Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-... more Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-solubilizing ability. However, the toxicity of bile salts increases with improving fat-solubilizing capability and so an optimal combination of efficient solubilization and low toxicity is necessary. To improve hydrophilicity (and decrease toxicity), we substituted hydroxyl groups of several natural bile acid (BA) molecules for oxogroups and studied their intrinsic molecular association behavior. Here we present the comparative Langmuir trough study of the two-dimensional (2D) association behavior of eight natural BAs and four oxoderivatives (traditionally called keto-derivatives) floated on an aqueous subphase. The series of BAs and derivatives showed systematic changes in the shape of the compression isotherms. Two types of association could be distinguished: the first transition was assigned to the formation of dimers through H-bonding and the second to the hydrophobic aggregation of ...

Research paper thumbnail of Selective antitumour activity and ERα molecular docking studies of newly synthesizedd-homo fused steroidal tetrazoles

Research paper thumbnail of Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives

European Journal of Medicinal Chemistry, 2012

New 17-picolyl and 17-picolinylidene androstane derivatives, 3e10, 15, 18, 19, 22 and 23, were sy... more New 17-picolyl and 17-picolinylidene androstane derivatives, 3e10, 15, 18, 19, 22 and 23, were synthesized starting from 17a-picolyl-androst-5-en-3b,17b-diol (1) and 17(Z)-picolinylidene-androst-5-en-3b-ol (2). Reaction of 1 with m-chloroperoxybenzoic acid gives 5a,6a-epoxy N-oxide derivative 3, or, with Jones reagent, 3,6-dione derivative 4; while 17a-picolyl-androst-5-en-3b,4a,17b-triol (5) or 3b,4b,17b-triol (6) derivatives are obtainable from 1 using SeO 2 in dioxane. Base-catalyzed tosyl group elimination from 7 or 9 affords AB conjugated derivatives 8 and 10. Oppenauer oxidation of 1 and 2 yields 4-en-3-one derivatives 11 and 12, which, with H 2 O 2 in 4 M NaOH, affords 4a,5a and 4b,5b-epoxides 13, 14, 16 and 17. New 4-methoxy-3-keto derivatives 15 and 18 were obtained from 13 and 14, or, with methanol in 4 M NaOH, from 16 and 17. Reduction of 11 with NaBH 4 gives 22, which was then acetylated to obtain 23. All new derivatives were screened for antitumor activity against human breast adenocarcinoma ERþ, MCF-7; human breast adenocarcinoma ER-, MDA-MB-231; prostate cancer AR-, PC-3; human cervix carcinoma, HeLa; and colon cancer, HT-29 cells; as well as one human non-tumor cell line, MRC-5. Compounds 3, 5, 6, 8, 10, 18, 19 and 22 exhibited significant antitumor activity against MDA-MB-231 breast cancer cells; while 5, 6 and 10 also showed strong cytotoxicity against HT-29. Only compound 19 exhibited significant activity against MCF-7 breast cancer cells. No compounds displayed cytotoxicity against non-tumor MRC-5 cells.

Research paper thumbnail of Synthesis and Biological Activity of Some 17a-Substituted Homolactones of Androst-5-ene Derivatives

Collection of Czechoslovak Chemical Communications, 2005

Some new 17a-homolactones were prepared from 3β-hydroxy-16-(hydroxyimino)androst-5-en-17-one (1) ... more Some new 17a-homolactones were prepared from 3β-hydroxy-16-(hydroxyimino)androst-5-en-17-one (1) as a starting compound, which was transformed first to the corresponding 17α-phenyl and 17α-benzyl derivatives 2 and 3. The structure of compound 3 was confirmed by X-ray structure analysis. Beckmann fragmentation of compounds 2 and 3 yielded 16,17-seco-cyano ketones 4-7, whose reduction with NaBH4 gave 16,17-seco-cyano alcohols 8-11, whereby the structure of compound 7 was established by X-ray structural analysis. Compounds 8-11 served as the starting compounds for obtaining lactones 12 and 13 in a reaction with potassium hydroxide in ethylene glycol. One-pot procedures were also developed for preparing 17a-homolactones 12, 13 and 16 from the hydroxyimino alcohols 2, 3 and 14. Compounds 12 and 13 showed an inhibitory activity against the enzyme aromatase (63 and 59%, respectively).

Research paper thumbnail of An intramolecular one-pot synthesis of steroidal triazoles via 1,3-dipolar cycloadditions of in situ generated diazo compounds

Tetrahedron Letters, 2009

A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular... more A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular 1,3-dipolar cycloaddition of a steroidal 16,17-seco-17-diazo-16-nitrile system. The structures of the products are established by X-ray and NMR studies. The in vitro antiproliferative activity of the steroidal triazoles against three tumor cell lines was evaluated.

Research paper thumbnail of New D-modified androstane derivatives as aromatase inhibitors

Steroids, 2001

Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy... more Starting from a 16-oximino derivative of 5-androstene the newly-synthesized 16-oximino-17-hydroxy-17-substituted derivatives 2–4 gave by the Beckmann fragmentation reaction the corresponding D-seco derivatives 6–9. Besides, in the case of the 17-hydroxy-17-methyl-16-oximino derivative 2, as a result of the rearrangement, the hydrolysis product 5 of the 16-oximino group with the opposite configuration at the C-17 was obtained. By the Oppenauer oxidation and/or

Research paper thumbnail of 17-Picolinylidene-androst-5-ene derivatives and their antiaromatase and cytotoxic activity

Arkivoc, 2010

Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were syn... more Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were synthesized. By oxidation of 3β-hydroxy derivative 2 with Jones reagent the corresponding 17(Z)-picolinylidene-androst-4-ene-3,6-dione 4 was obtained. The Oppenauer oxidation of 2 yielded 4-en-3-one derivative 3, which reacted with potassium-t-butoxide in t-butanol to give 4ene-3,6-dione 4 and 4-hydroxy-4,6-dien-3-one 5 derivatives. Nitration of compound 1 afforded 6-nitro-5-ene derivative 6. The reaction of compound 3 with NaBH 4 in ethanol afforded stereoselectively the 3β-hydroxy-4-ene derivative 7, the acetylation of which gave 3β-acetoxy derivative 8 whereas 17-picolinylidene derivatives 9-14 have been synthesized earlier. Compounds 4-8 were tested on potential inhibitory activity against the enzyme aromatase. Satisfactory inhibitory activity showed compounds 4, 5, 7 and 8. Cytotoxicity in vitro against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231 and prostate cancer AR-, PC-3) and normal fetal lung fibroblasts, MRC-5, of compounds 1-14 was also evaluated. Strong cytotoxic activity showed compound 5 against MDA-MB-231 (IC 50 9.3 µM) and compound 7 against PC-3 (IC 50 10.1 µM). All compounds were not toxic to healthy MRC-5 cells.

Research paper thumbnail of Synthesis and biological evaluation of some new A,B-ring modified steroidal d-lactones

Steroids, 2008

Starting from the d-homo lactones of androst-4-en-3-one 3 and 4, prepared from 1 and 2, the new 1... more Starting from the d-homo lactones of androst-4-en-3-one 3 and 4, prepared from 1 and 2, the new 17a homolactones 5–12, 14 and 15, were synthesized. The 4-hydroxy compounds 9 and 10 were obtained through the reaction of 4α, 5α-(5 and 7) and 4β, 5β-(6 and 8) ...

Research paper thumbnail of Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acids on verapamil hydrochloride in biophysical-chemical model experiments

Journal of the Serbian Chemical Society, 2011

Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acid... more Effect of sodium salts of 3α,12α-dihydroxy-7-oxo-5β-cholanoic and 3,7,12-trioxo-5β-cholanoic acids on verapamil hydrochloride in biophysical-chemical model experiments

Research paper thumbnail of Stereospecific synthesis of (−)- allo-muscarine from d-glucose

Carbohydrate Research, 1996

ABSTRACT The key chiral synthon in a novel synthesis of (-)- allo -muscarine from D-glucose has b... more ABSTRACT The key chiral synthon in a novel synthesis of (-)- allo -muscarine from D-glucose has been prepared by three independent routes. The most efficient one includes a four-step conversion via the 4- O -benzoyl derivatives of starting 2,5-anhydro-3,5-di- O -methanesulfonyl-L-idose ethylene acetal ( 2a ) into 2,5-anhydro-3,6-dideoxy-L- lyxo- hexose ethylene acetal ( 4b ). The intermediate 4b was efficiently converted into the chiral synthon 2,5-anhydro-4- O -benzoyl-3,6-dideoxy-L- arabino -hexose ( 4c ) by Mitsunobu reaction.

Research paper thumbnail of 17-Picolinylidene-substituted steroid derivatives and their antiaromatase and cytotoxic activity

ARKIVOC, 2009

Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were syn... more Starting from 17(Z)-picolinylidene-androst-5-en-3β-yl acetate 1, the new derivatives 4-8 were synthesized. By oxidation of 3β-hydroxy derivative 2 with Jones reagent the corresponding 17(Z)-picolinylidene-androst-4-ene-3,6-dione 4 was obtained. The Oppenauer oxidation of 2 yielded 4-en-3-one derivative 3, which reacted with potassium-t-butoxide in t-butanol to give 4ene-3,6-dione 4 and 4-hydroxy-4,6-dien-3-one 5 derivatives. Nitration of compound 1 afforded 6-nitro-5-ene derivative 6. The reaction of compound 3 with NaBH 4 in ethanol afforded stereoselectively the 3β-hydroxy-4-ene derivative 7, the acetylation of which gave 3β-acetoxy derivative 8 whereas 17-picolinylidene derivatives 9-14 have been synthesized earlier. Compounds 4-8 were tested on potential inhibitory activity against the enzyme aromatase. Satisfactory inhibitory activity showed compounds 4, 5, 7 and 8. Cytotoxicity in vitro against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231 and prostate cancer AR-, PC-3) and normal fetal lung fibroblasts, MRC-5, of compounds 1-14 was also evaluated. Strong cytotoxic activity showed compound 5 against MDA-MB-231 (IC 50 9.3 µM) and compound 7 against PC-3 (IC 50 10.1 µM). All compounds were not toxic to healthy MRC-5 cells.

Research paper thumbnail of A novel route to 2-deoxy-2-iodo-d-mannopyranose derivatives

Carbohydrate Research, 1992

1,5-Anhydro-2-deoxy-D-hex-1-enitols are versatile synthons'*2. Various functional groups, such as... more 1,5-Anhydro-2-deoxy-D-hex-1-enitols are versatile synthons'*2. Various functional groups, such as chloro3, fluoro4-7, bromo8, or iodo'-I', may be introduced at position 2 by either direct or indirect addition of suitable agents across the double bond. Iodination of o-glucal triacetate, using iodine and silver benzoate in dry ben-zene9*10, iodine and silver acetate in methanol', N-iodosuccinimide in dry methanol'*, or iodonium bis(2,4,6-trimethylpyridine)perchlorate12, have been described, corresponding to the formal addition of alkyl or acyl hypoiodite across the double bond. However, the formation of free 2-deoxy-2-iodo sugars has not been described hitherto. We now report a formal electrophilic addition of "hypoiodous acid" to 3,4,6-tri-0-acetyl-o-glucal'3 (1) and 3,4-di-0-acetyl-6-0-tosyl-D-glucal'4 (2). Depending on the buffer system used and the pH, a mixture of the 2-deoxy-2-iodo esters 3 of 5 together with the corresponding 2-deoxy-2-iodo sugars 4 or 6, or only 4 or 6, were obtained. The compounds obtained could be used for the preparation of 2-deoxy sugars or Brigl's anhydrides. Thus, treatment of 1 or 2 with iodine in tert-butyl alcohol in the presence of acetate buffer (pH 5, room temperature, 3 h) gave a mixture of the 2-deoxy-2iodo-manno-esters 3 or 5 together with the corresponding Zdeoxy-Ziodo-a-o-mannopyranose derivatives 4 or 6, in the ratio 3 : 1. However, when this reaction was carried out in the presence of a phosphate or carbonate buffer (pH 6-7, room temperature, 3 h), the 2-deoq&iodo-aD -mannopyranose derivatives 4 or 6 were the only isolable products (50-60%). The structures of 3-6 were confirmed by the NMR data (Table I> and [cu], values. The above procedure for the preparation of the 2-deoxy-2-iodo-cuD -manno

Research paper thumbnail of Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives

This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright

Research paper thumbnail of The effect of hydroxyl moieties and their oxo-substitution on bile acid association studied in floating monolayers

Research paper thumbnail of An alternative synthesis of (+)- epiallo-muscarine from d-glucose

Carbohydrate Research, 1995

Research paper thumbnail of An intramolecular one-pot synthesis of steroidal triazoles via 1,3-dipolar cycloadditions of in situ generated diazo compounds

Tetrahedron Letters, 2009

A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular... more A novel synthetic route is reported for the preparation of steroidal triazoles via intramolecular 1,3-dipolar cycloaddition of a steroidal 16,17-seco-17-diazo-16-nitrile system. The structures of the products are established by X-ray and NMR studies. The in vitro antiproliferative activity of the steroidal triazoles against three tumor cell lines was evaluated.