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The present study is concerned with the oxidative behaviour of unsaturated and epoxy 5-oxo-5,10-secosteroids in the presence of m-CPBA or TFAA-UHP as oxidants in order to investigate potential parameters controlling the chemoselectivity and regioselectivity. In the study we discovered a striking difference in the chemical behaviour of stereoisomeric compounds, (Z)- and (E)-3 beta-acetoxy-5,10-secocholest-1(10)-en-5-ones, as well as 1S,10R- and 1R,10R-epoxides. The secoketones were oxidized with exclusively C-6 migration and Baeyer-Villiger rearrangement product formation, whereas their stereoisomers provided the ring-contracted products, without lactone formation. The preferred conformation of expanded and contracted rings was established by NOESY correlations. The structures of two obtained lactones were also confirmed by X-ray analysis. The mechanistic and stereochemical aspects of these transformations are discussed.

Two sets of new peptides incorporating fulleropyrrolidine units Fp-GABAn-Glym-OtBu have been designed, synthesized and completely characterized. In the first series the chain contained only GABA (?-aminobutyric) residues, whereas in the second one glycine moieties were also inserted as well as GABA. Most of the target compounds were prepared by DCC/DMAP-assisted coupling of previously synthesized GABA-containing fulleropyrrolidinic acid and corresponding C-protected small peptides, although for two fulleropeptides [3+2] cycloadditions of azomethine ylides to C60 were employed. All new compounds were characterized by standard spectroscopic methods. Complete assignments of peptide spin systems were achieved by extensive NMR analysis (1H, 13C, H,H-COSY, HSQC, HMBC and TOCSY).

The reactions of 17 alpha-hydroxyprogesterone with Lawesson's reagent (LR) in toluene, CH2Cl2 and/or CCl4 gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D H-1-C-13 spectra (HSQC and HMBC) and homo-nuclear 2D spectra (NOESY) enabled complete H-1 and C-13 assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia sauna, were evaluated. All tested compounds showed strong antifungal activity.

Two sets of new peptides incorporating fulleropyrrolidine units Fp-GABAn-Glym-OtBu have been designed, synthesized and completely characterized. In the first series the chain contained only GABA (?-aminobutyric) residues, whereas in the second one glycine moieties were also inserted as well as GABA. Most of the target compounds were prepared by DCC/DMAP-assisted coupling of previously synthesized GABA-containing fulleropyrrolidinic acid and corresponding C-protected small peptides, although for two fulleropeptides [3+2] cycloadditions of azomethine ylides to C60 were employed. All new compounds were characterized by standard spectroscopic methods. Complete assignments of peptide spin systems were achieved by extensive NMR analysis (1H, 13C, H,H-COSY, HSQC, HMBC and TOCSY).

In this paper a synthetic pathway to the modified 5,10:13,14-bisfragmentation cholestane derivatives 8-14 is described. The synthesis involves introduction of the 5α- and 14α-hydroxyl groups in the cholestane molecule and subsequent cleavage of the C(5)-C(10) bond in 5α,14α-dihydroxycholestan-3β-yl acetate (4) with the HgO/I2 reagent and the C(13)-C(14) bond in the stereoisomeric 14α-hydroxy-5,10-secosteroids 5 and 6 with the Pb(OAc)4/I2 reagent. Complete and unambiguous 1H and 13C NMR resonance assignments of the obtained secosteroids, as well as the solution conformations of their 10- and 9-membered rings were determined by extensive analysis of 1D and 2D NMR spectral data. The structures and the solid-state conformations of 5,10-secosteroids 5-7 were confirmed by X-ray analysis. All diseco-compounds have a novel 5,10:13,14-disecocholestane skeleton.

U оvој dоktоrskој disеrtаciјi ispitаn је, i еkspеrimеntаlnо i rаčunаrski, mеhаnizаm rеаkciје kеtоnа sа brоmоfоrmоm. Еkspеrimеntаlnо ispitајući оvај mеhаnizаm rаzviјеna је i оptimizоvаnа nоvа „one-pot“ mеtоdа zа sintеzu α,β-nеzаsićеnih kаrbоksilnih kisеlinа. Меtоdа оbuhvаtа rеаkciјu kеtоnа sа brоmоfоrmоm i litiјum-hidrоksidоm u аlkоhоlnim rаstvаrаčimа i vоdоm kао kо-rаstvаrаčеm kоја је kаtаlizоvаnа fаznim kаtаlizаtоrimа (TEBA, 18-C-6). Rеаkciја sе izvоdi nа sоbnој tеmpеrаturi u tоku 24 čаsа. Kоnjugоvаnе kisеlinе nаstајu iz cikličnih i аrоmаtičnih kеtоnа, dоk α-brоmkаrbоksilnе kisеlinе nаstајu iz еtil-4-оksо-pipеridin-1-kаrbоksilаtа i tеrc-butil-4-оksо-pipеridin-1-kаrbоksilаtа.Prоrаčuni su rаđеni nа sistеmu ciklоhеksаnоn-brоmоfоrm dа bi sе оbјаsnilо оtvаrаnjе еpоksidnоg prstеnа nuklеоfilnоm rеаkciјоm dihаlоgеnеpоksidа. U оvој rеаkciјi, nаstајаnjе dibrоmеpоksidа је klјučnа fаzа kоја оdrеđuје udео i stеrеоhеmiјu prоizvоdа. Svаkа rеаkciоnа shеmа sаdrži еpоksid kао klјučniintеrmеdiјеr. Prеtpоstаvlјеnа su i prоučаvаnа tri rеаkciоnа mеhаnizmа kојim nаstајu 1-ciklоhеksеnkаrbоksilnа kisеlinа, 1-hidrоksiciklоhеksаnkаrbоksilnа kisеlinа 1-brоmciklоhеksаnkаrbоksilnа kisеlinа, kао prоizvоdi. Prоrаčuni pоkаzuјu dа su svа tri rеаkciоnа putа еgzоtеrmnа. Rеаkciоni put kојim nаstаје 1¬ ciklо-hеksеnkаrbоksilnа kisеlinа kао prоizvоd је nајvеrоvаtniјi i nе uklјučuје intеrmеdiјеr.Svim sintеtizоvаnim kisеlinаmа оdrеđеnа је in vitro аntiprоlifеrаtivnа аktivnоst prеmа HeLa ćеliјskim liniјаmа. U nаmеri dа sе оdrеdi i nеpоžеlјnа citоtоksičnоst оvih јеdinjеnjа, оdrеđеnа је citоtоksičnа аktivnоst prеmа nеstimulisаnim i stimulisаnim ćеliјаmа PBMC. Vеćinа sintеtizоvаnih kisеlinа pоkаzuје slаbо аntiprоlifеrаtivnо dејstvо i imајu IC50 od 122,2 do 192 μM. Nајаktivniја је 1- ciklо-dоdеcеnkаrbоksilnа kisеlinа (IC50=122 μM prеmа HeLa ćеliјаmа). Ispitivаnе kisеlinе pоkаzuјu tаkоđе vеоmа slаbu аktivnоst prеmа ćеliјаmа limfоcitа (PBMC i PBMC+PHA) sа IC50 > 200 μM., In this Thesis, the mechanism of reaction of bromoform with ketones was examined by experimental and computing. A new one-pot reaction for synthesis of α,β-unsaturated carboxylic acids was developed.Phase-transfer catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent with TEBA or 18-C-6 as catalyst, result in the formation of α,β-unsaturated carboxylic acids. The reaction was performed at room temperature for 24 h. Corresponding conjugated acids were obtained from cyclic or aromatic ketones, while bromo acids were obtained from 4 oxo-piperidine-1-carboxylic acid ethyl ester and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester.To elucidate the ring opening nucleophilic reactions of dihaloepoxides the extensive calculations were done on a model system cyclohexanone - bromoform. In this reaction the formation of dibromoepoxide is postulated as a key step determining distribution and stereochemistry of products. Every reaction scheme involves epoxide as a key intermediate. Three major products, 1¬ cyclohexene-1-carboxylic acid, 1-bromocyclohexane carboxylic acid and 1-hydroxy¬cyclohexane carboxylic acid could be obtained by three different competing reaction pathways. Calculations showed that all pathways are exothermic. Reaction pathway for synthesis of 1¬ cyclohexene-1-carboxylic acid is most convenient, and does not include any intermediate.The antiproliferative activity of obtained acids toward malignant cell lines was evaluated in this work, too. With the aim to determine the undesirable cytotoxic effect of investigated compounds on immune competent cells the normal peripheral blood mononuclear cells were used as target cells, too. The majority of synthesized conjugated acids exert moderate antiproliferative activity in vitro toward HeLa, having IC50 values from 122.20 to 192 μM. The most active compound is 1-cyclododecene-1-carboxylic acid, (IC50=122 μM toward HeLa cells). All examined compounds did not affect pr

U оvој dоktоrskој disеrtаciјi ispitаn је, i еkspеrimеntаlnо i rаčunаrski, mеhаnizаm rеаkciје kеtоnа sа brоmоfоrmоm. Еkspеrimеntаlnо ispitајući оvај mеhаnizаm rаzviјеna је i оptimizоvаnа nоvа „one-pot“ mеtоdа zа sintеzu α,β-nеzаsićеnih kаrbоksilnih kisеlinа. Меtоdа оbuhvаtа rеаkciјu kеtоnа sа brоmоfоrmоm i litiјum-hidrоksidоm u аlkоhоlnim rаstvаrаčimа i vоdоm kао kо-rаstvаrаčеm kоја је kаtаlizоvаnа fаznim kаtаlizаtоrimа (TEBA, 18-C-6). Rеаkciја sе izvоdi nа sоbnој tеmpеrаturi u tоku 24 čаsа. Kоnjugоvаnе kisеlinе nаstајu iz cikličnih i аrоmаtičnih kеtоnа, dоk α-brоmkаrbоksilnе kisеlinе nаstајu iz еtil-4-оksо-pipеridin-1-kаrbоksilаtа i tеrc-butil-4-оksо-pipеridin-1-kаrbоksilаtа.Prоrаčuni su rаđеni nа sistеmu ciklоhеksаnоn-brоmоfоrm dа bi sе оbјаsnilо оtvаrаnjе еpоksidnоg prstеnа nuklеоfilnоm rеаkciјоm dihаlоgеnеpоksidа. U оvој rеаkciјi, nаstајаnjе dibrоmеpоksidа је klјučnа fаzа kоја оdrеđuје udео i stеrеоhеmiјu prоizvоdа. Svаkа rеаkciоnа shеmа sаdrži еpоksid kао klјučniintеrmеdiјеr. Prеtpоstаvlјеnа su i prоučаvаnа tri rеаkciоnа mеhаnizmа kојim nаstајu 1-ciklоhеksеnkаrbоksilnа kisеlinа, 1-hidrоksiciklоhеksаnkаrbоksilnа kisеlinа 1-brоmciklоhеksаnkаrbоksilnа kisеlinа, kао prоizvоdi. Prоrаčuni pоkаzuјu dа su svа tri rеаkciоnа putа еgzоtеrmnа. Rеаkciоni put kојim nаstаје 1¬ ciklо-hеksеnkаrbоksilnа kisеlinа kао prоizvоd је nајvеrоvаtniјi i nе uklјučuје intеrmеdiјеr.Svim sintеtizоvаnim kisеlinаmа оdrеđеnа је in vitro аntiprоlifеrаtivnа аktivnоst prеmа HeLa ćеliјskim liniјаmа. U nаmеri dа sе оdrеdi i nеpоžеlјnа citоtоksičnоst оvih јеdinjеnjа, оdrеđеnа је citоtоksičnа аktivnоst prеmа nеstimulisаnim i stimulisаnim ćеliјаmа PBMC. Vеćinа sintеtizоvаnih kisеlinа pоkаzuје slаbо аntiprоlifеrаtivnо dејstvо i imајu IC50 od 122,2 do 192 μM. Nајаktivniја је 1- ciklо-dоdеcеnkаrbоksilnа kisеlinа (IC50=122 μM prеmа HeLa ćеliјаmа). Ispitivаnе kisеlinе pоkаzuјu tаkоđе vеоmа slаbu аktivnоst prеmа ćеliјаmа limfоcitа (PBMC i PBMC+PHA) sа IC50 > 200 μM., In this Thesis, the mechanism of reaction of bromoform with ketones was examined by experimental and computing. A new one-pot reaction for synthesis of α,β-unsaturated carboxylic acids was developed.Phase-transfer catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent with TEBA or 18-C-6 as catalyst, result in the formation of α,β-unsaturated carboxylic acids. The reaction was performed at room temperature for 24 h. Corresponding conjugated acids were obtained from cyclic or aromatic ketones, while bromo acids were obtained from 4 oxo-piperidine-1-carboxylic acid ethyl ester and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester.To elucidate the ring opening nucleophilic reactions of dihaloepoxides the extensive calculations were done on a model system cyclohexanone - bromoform. In this reaction the formation of dibromoepoxide is postulated as a key step determining distribution and stereochemistry of products. Every reaction scheme involves epoxide as a key intermediate. Three major products, 1¬ cyclohexene-1-carboxylic acid, 1-bromocyclohexane carboxylic acid and 1-hydroxy¬cyclohexane carboxylic acid could be obtained by three different competing reaction pathways. Calculations showed that all pathways are exothermic. Reaction pathway for synthesis of 1¬ cyclohexene-1-carboxylic acid is most convenient, and does not include any intermediate.The antiproliferative activity of obtained acids toward malignant cell lines was evaluated in this work, too. With the aim to determine the undesirable cytotoxic effect of investigated compounds on immune competent cells the normal peripheral blood mononuclear cells were used as target cells, too. The majority of synthesized conjugated acids exert moderate antiproliferative activity in vitro toward HeLa, having IC50 values from 122.20 to 192 μM. The most active compound is 1-cyclododecene-1-carboxylic acid, (IC50=122 μM toward HeLa cells). All examined compounds did not affect pr

Four new fullero-steroids were synthesized starting from gamma-aminobutyric acid (GABA)-incorporated fulleropyrrolidine and corresponding sterols. The synthesis, characterization, preliminary study on in vitro antioxidant activity as well as the steady state photophysical properties are presented. All synthesized compounds showed antioxidant activity 2-3-fold higher than the parent fullerene. The most active compound appeared to be as potent as standard antioxidant BHT (2,6-di-tert-butyl-4-methylphenol). Also, all of them fluoresce 6-8-fold stronger than C-60, thus representing potential irradiation assisted pro-oxidants. With significantly increased lipophilicity, it could be expected that attached steroidal subunit enables better penetration Of C60 to living cell membranes, thus facilitating its antioxidant activity. Based on all obtained results, newly synthesized covalent fullero-steroidal conjugates represent good candidates for potential antioxidants as well as pro-oxidants. (c) 2007 Elsevier Ltd. All rights reserved.

The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3) and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B-homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for their possible effects against two human tumor cell lines, cervical carcinoma (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1-6, exerted a dose-dependent antiproliferative effect toward cell lines used in experimental design, showing high selectivity in their action for tumor cells in comparison to normal immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2, 3 and 4 exhibited a very high but selective antitumor activity, by inducing apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells). Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control, healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible reasons for profound differences in the effects of this spectrum of steroidal compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs are discussed. The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined.

We report herein the synthesis of a novel modified steroid with two rigidly positioned amino acids in C- and N-protected forms (Gly-OtBu and N-Fmoc-l-Phe) at the angular positions (C-18 methylamino group and C-19 carboxylic function) of the steroid nucleus via amide bonds, starting from 18-cyanopregnenolone acetate over 10 steps. In an attempt to gain more insight into the structural and conformational features of this novel 18-Phe,19-Gly-containing steroidal compound, we describe the detailed 2D NMR spectral analysis. Despite the large size and the conformational flexibility of the amino acid units in this molecule, conformational analysis by NOESY connectivities showed the existence of mainly one conformation (∼95%) in CDCl3 solution with approximately parallel orientation of the phenylalanine and glycine moieties.

The conformations of (Z)‐ and (E)‐5‐oxo‐B‐nor‐5,10‐secocholest‐1(10)‐en‐3β‐yl acetates (2 and 3, resp.) were examined by a combination of X‐ray crystallographic analysis and NMR spectroscopy, with emphasis on the geometry of the cyclononenone moiety. The 1H‐ and 13C‐NMR spectra showed that the unsaturated nine‐membered ring of (E)‐isomer 3 in C6D6 and (D6)acetone solution exists in a sole conformation of type B1, which is similar to its solid‐state conformation. The (Z)‐isomer 2 in C6D6, CDCl3, and (D6)acetone solution, however, exists in two conformational forms of different families, with different orientation of the carbonyl group, the predominant form (85%) corresponding to the conformation of type A1 and the minor (15%) to the conformation A2 present also in the crystalline state. In this solid‐state conformations of the nine‐membered ring of both compounds, the 19‐Me and 5‐oxo groups are ‘β’‐oriented. The NMR analysis suggests that the nine‐membered ring of 4 has a conformation of type C1 in CDCl3 solution.

Beckmann rearrangement of (Z)-cholest-4-en-6-one oxime (4) (prepared in 4 steps starting from cholest-5-en-3β-ol ο1)) with thionyl chloride in dioxane solution afforded an enamide-type lactam, i.e. 7-aza-B-homocholest-4-en-6-one (6) as a single product. Photoreaction of the same compound in methanol or benzene-acetic acid solution gave a mixture of products, with the formation of the parent ketone 3 and the occurrence of Z/E isomerization, while the lactam 6 was obtained only when the reaction was performed in methanol and then in very low yield (7%)., Bekmanovo premeštanje (Z)-holest-4-en-6-on oksima (4) (koji je dobijen u 4 faze, polazeći od holest-5-en-3 β-ola (1)) sa tionil-hloridom u dioksanskom rastvoru, kao jedini proizvod daje laktam enamidnog tipa, tj. 7-aza-B-homoholest-4-en-6-on (6). Fotoreakcijom istog jedinjenja u metanolu ili u rastvoru benzen-sirćetna kiselina, nastaje smesa proizvoda koju čine polazni keton 3 i proizvodi Z/E izomerizacije, dok je laktam 6 dobiven u vrlo niskom prinosu (7%) samo u metanolnom rastvoru.

The acid-catalyzed reaction of (Z)- and (E)-B-nor-5,10-seco-ketones 2 and 3 resulted in an intramolecular cyclization to give the 5-hydroxy-A-nor-1β,5β-10(19)-methylidene derivative 8, the 5β-hydroxy-A-nor-1(10)-unsaturated compound 9 and the 5β,10β-dihydroxy A-nor-product 10, from the (Z)-isomer and the 5-hydroxy-A-nor-1β,5β-10(19)-methylidene product 11, from the (E)-isomer. Upon UV-irradiation, the (Z)- and (E)-seco-ketones 2 and 3 underwent a reversible (Z)/(E) and (E)/(Z)-isomerization and in addition to a transannular photocyclization to afford the 10(19)-methylidene derivatives 8 and 11, respectively, while photolysis of the 10(19)-methylidene-B-nor-5,10-seco-ketone 4 gave the oxetane derivative 12., Kiselo-katalizovana reakcija (Z)- i (E)-B-nor-5,10-seko-ketona 2 i 3 rezultuje u intramolekulskoj ciklizaciji dajući 5-hidroksi-A-nor-1β,5β-10(19)-metilidenski derivat 8, 5β-hidroksi A-nor-1(10)-nezasićeno jedinjenje 9 i 5β,10β-dihidroksi-A-nor-proizvod 10, iz Z-izomera, i 5-hidroksi-A-nor-1β,5β-10(19)-metilidenski proizvod 11, iz E-izomera. (Z)- i (E)-Seko- ketoni 2 i 3 UV-ozračivanjem podležu reverzibilnoj (Z)/(E) odnosno (E)/(Z) izomerizaciji, kao i transanularnoj fotociklizaciji dajući 10(19)-metilidenske derivate 8 odnosno 11, dok se fotolizom 10(19)-metilidenskog-5,10-seko-ketona 4 gradi oksetanski derivat 12.

5-hydroxy-1-oxo-5α-cholestan-3β-yl acetate (11) was prepared in 5 steps starting from (E)-3β-acetoxy-5,10-seco-1(10)-cholesten-5-one (6). Treatment of the 1-oxo-5-hydroxy derivative 11 with lead tetraacetate (LTA) (under thermal or hypoiodite conditions) or with mercuric oxide/iodine (HgO/I2) reagent resulted in the oxidative β-fragmentation of the C(5)–C(10) bond affording 1,5-dioxo-5,10-secocholest-10(19)-en-3β-yl acetate (12), in different yields, depending on the reagent. Also the stereochemistry of the 1β,6β-cyclization product 13, formed by transannular cyclization of the 1,5-diketone 12 on silica gel, is discussed in this work., Sintetizovan je 5-hidroksi-1-okso-5α-holestan-3β-il-acetata (11) u 5 faza polazeći od (E)- 3β-acetoksi-5,10-seko-1(10)-holesten-5-ona (6). Dejstvom olovo-tetraacetata (LTA) (pod termičkim ili hipojoditnim uslovima), ili merkuri-oksid/jodnog reagensa (HgO/I2) na 1-okso-5-hidroksi derivat 11, vrši se oksidativna β-fragmentacija njegove C(5)–C(10) veze, pri čemu se dobija 1,5-diokso-5,10-sekoholest-10(19)-en-3β-il-acetat (12), u različitim prinosima u zavisnosti od upotrebljenog reagensa. Takođe, diskutovana je stereohemija 1β,6β-ciklizacionog proizvoda 13, nastalog intramolekulskom ciklizacijom 1,5-diokso-5,10-seko jedinjenja 12 na silika gelu.

B-Norcholestane epoxide 2 is reduced with lithium aluminium hydride to give either the 3β,6α-diol 3 or the corresponding 3β,5α-diol 4, depending on the quality of the reducing reagent employed. Aplausible mechanistic explanation of the obtained results is suggested., Redukcijom B-norholestan-epoksida 2 pomoću litijum-aluminijum-hidrida dobijeni su odgovarajući 3β,6α-diol 3 ili 3β,5α-diol 4, u zavisnosti od kvaliteta upotrebljenog redukcionog reagensa. Predloženo je verovatno mehanističko tumačenje dobijenih rezultata.

The crystal structure of 14-oxo-13,14-seco-5α-cholest-13(18)-en-3β-yl acetate (2), obtained (in addition to the (E)-Δ12-isomer 3) by oxidative fragmentation of the C(13)-C(14) bond of 14α-hydroxy-5α-cholestan-3β-yl acetate (1), was determined by X-ray analysis. In addition, the configurations of the acetoxy derivatives 4-6, formed by the thermal lead tetraacetate oxidation of 1, were deduced from the relevant 1H-NMR parameters., Kristalna struktura 14-okso-13,14-seko-5α-holest-13(18)-en-3β-il-acetata (2). koji se dobiva (pored (E)-Δ12-izomera 3) oksidativnom fragmentacijom C(13)-C(14) veze 14α-hidroksi-5α-holestan-3β-il-acetata (1) određena je analizom X-zraka. Pored toga, konfiguracije njegovih acetoksi derivata 4-6, koji se grade pri termičkoj olovo-tetraacetatnoj oksidaciji, izvedene su na osnovu odgovarajućih 1H-NMR parametara.

Oxidations of 14α‐hydroxy‐5α‐cholestan‐3β‐yl acetate (5) with lead tetraacetate under thermal or photolytic conditions or in the presence of iodine proceed mainly by fragmentation of the C(13)−C(14) bond to give as the primary products the 13,18‐didehydro‐13,14‐seco derivative 6 and the (E )‐Δ12‐13,14‐seco ketone 11, respectively. Further transformations of these compounds under conditions of their formation afforded, in addition, the acetoxy derivatives 7 – 9 (from 6), and the D‐homo‐C‐nor compound 12 and (12R,13R)‐epoxide 13 (from 11). Unexpectedly, the photolytic lead‐tetraacetate oxidation of 5 resulted partly (to ca. 20%) in a reversible fragmentation involving scission and recombination of the C(8)−C(14) bond followed by formation of the 14β,22‐ether 10. Possible mechanisms for the observed transformations are discussed.

The two structurally similar 20‐phenyl‐ and 20‐(4‐methoxyphenyl)‐11‐(nitrosooxy)pregnan‐20‐ol derivatives 4 and 7 behave differently under photolytic conditions, the former nitrous acid ester affording, as a main product, the benzo‐fused hexacyclic compound 9, and the latter the 21‐nitro derivative 12. Mechanistic aspects of these transformations are discussed.

Photochemically induced HgO/I2 oxidation of cholest-5-en-3α-ol (6) and cholest-5-en-3β-ol (7) afforded (Scheme 3) products arising from the corresponding alkoxy radicals (12, 13 and 14a,b) and from attack of the I2O intermediate at the olefinic double bond (epoxides 15a and 16a,b respectively). With cholest-5-ene-1α,3β-diol 3-acetate (8) and cholest-7-ene-3β,5α-diol 3-acetate (9) the HgO/I2 oxidation led to unresolvable complex mixtures (Scheme 5). With the same reagent cholest-5-en-3α-ol acetate (10) and cholest-5-en-3β-ol acetate (11) underwent exclusively attack by I2O, to give epoxides 20a,b, iodohydrin 21, and rearranged products 19 and 22 (Scheme 7), in the case of 10, and predominantly epoxides 23a,b (Scheme 8), in the case of 11. © 1994.

The oxidation of androst-4-ene-3β,9α,17β-triol 3,17-diacetate (2) with lead tetraacetate resulted mainly In β-fragmentation of the C(9)-C(10) bond to give a mixture of 10α- and 10β-acetoxy-Δ4-unsaturated 9,10-seco-steroidal ketones (3a and 3b) as the minor components (in ~7% yield) and the rearranged 4β-acetoxy-Δ5(10) -unsaturated 9,10-seco-9-ketone (4) as the major product (in 61% yield). Unexpectedly, when the same substrate (2) was subjected to the mercuric oxide - iodine oxidation, it underwent predominantly α-epoxidation of the olefinic double bond to produce the 4α,5α-epoxy derivative (5) (in 58% yield). © 1988.

Unsubstituted medium‐ring 1,2‐epoxycycloalkanes and certain vic‐epoxyalkanes are reduced to the corresponding alcohols very slowly when LiAlH4 alone is used as reducing agent. However, the combination of LiAlH4 and AlCl3, in a 2:1 molar ratio (with respect to 1 mol‐equiv. of epoxide) used in refluxing Et2O, greatly enhances these reductions, rendering them of interest for practical purposes.