Leszek Siergiejczyk

13C-NMR study of 4-azasteroids in solution and solid state.

A group of biologically active 4-azasteroids was studied by 13C-NMR spectroscopy in solution and in the solid phase. A full assignment of signals in the spectra of samples in chloroform was performed for thirteen 4-azasteroids using two-dimensional techniques. Substituent and steric effects of a nitrogen atom, and their influence on chemical shifts of the neighboring carbon atoms are discussed. CP MAS spectra were obtained for five 4-azasteroids including finasteride. The spectra confirmed polymorphism of the latter compound. In addition to the polymorphic forms that are already known, a new molecular complex of finasteride with dioxane is reported.

The possible association between serum cholesterol concentration and decreased bone mineral density as well as intravertebral marrow fat in HIV-1 infected patients

Metabolic and morphologic abnormalities as well as disturbances in bone mineral density (BMD) are prevalent among HIV-infected patients, particularly during highly active antiretroviral treatment (HAART) [1–3]. Hyperlipidaemia may affect up to 60–80% of HIV-infected patients treated with protease inhibitors (PI) and is commonly associated with abnormalities in body composition [1]. Osteoporosis and osteopenia affects at least a half of antiretroviral treated HIV-infected population [2]. Even though the relationship between metabolic and bone alterations has not been clearly established, it has received increased attention in the recent years [4]. In the general population BMD is correlated with serum lipids in one study: negatively for HDL cholesterol and positively for triglycerides and LDL cholesterol [5]. Moreover, data emerging from other clinical studies demonstrate that lipid-lowering agents, mainly statins, enhance bone mineralization and may reduce the risk of osteoporotic fractures in non-HIV infected patients [6]. The mechanism underlying this relationship remains largely unknown. Some authors cite the role of lipid oxidation products in osteoclast differentiation and osteoblast inhibition, which results in the induction of bone resorption [7]. The most commonly used technique to assess BMD is dual-energy X-ray absorptiometry. In the recent years, vertebral marrow fat content as assessed by proton magnetic resonance spectroscopy (1H-MRS) has been recommended as a valuable tool of the evaluation of bone disorders [8]. Schellinger et al. [9] demonstrated a relationship between bone marrow fat content and bone mineral density and suggested that the combination of DEXA and MR spectroscopy may contribute to higher accuracy in estimating bone weakeness. The exact mechanism of this relationship is unclear, though the presence of decreased marrow fat and osteopenia in HIV-infected population has been reported [10]. The aim of our study is to evaluate the relationship between abnormalities in serum lipids and BMD and intravertebral marrow fat content in HIVinfected individuals. We performed a cross-sectional analysis of 55 HIVinfected individuals (39 males, 16 females, aged from 20 to 53 years, median 37) treated in the outpatient Clinic of Infection Correspondence

Hindered Rotation in New Air-Stable Ruthenium Olefin Metathesis Catalysts with Chromanylmethylidene Ligands

Three new ruthenium complexes with chromanylmethylidene ligands were synthesized and dynamic NMR analysis of these compounds was carried out. The activation energy for the C–Ru rotation was measured for the first time and found to be of ~60 kJ mol–1. The complexes may potentially serve as latent catalysts for olefin metathesis – they promote the simple ring-closing metathesis reactions very slowly at room temperature, but are much more active at slightly elevated temperatures. No asymmetric induction was observed when the chiral α-tocopherol-derived catalyst was used.

Electrochemical synthesis of glycoconjugates from activated sterol derivatives.

Several derivatives of cholesterol and other 3β-hydroxy-Δ(5)-steroids were prepared and tested as sterol donors in electrochemical reactions with sugar alcohols. The reactions afforded glycoconjugates with sugar linked to a steroid moiety by an ether bond. Readily available sterol diphenylphosphates yielding up to 54% of the desired glycoconjugate were found to be the best sterol donors.

Photoinduced Isomerization of 23-Oxosapogenins: Conformational Analysis and Spectroscopic Characterization of 22-Isosapogenins

The first synthesis of 22-isospirostane derivatives is described. They were obtained by photochemical isomerization of 23-oxosapogenins. The structure of 23-oxo-22-isotigogenin acetate (12) was proved by a single crystal X-ray diffraction, while structures of 23-oxo-22-isodiosgenin acetate (13) and 23-oxo-22-isosarsasapogenin acetate (14) were elucidated by spectroscopic methods. 22-Isodiosgenin acetate (17) was obtained by NaBH(4) reduction of the 23-oxo derivative 13 followed by the two-step Barton-McCombie deoxygenation procedure. Conformational analysis of 22-iso compounds was carried out with CD and NMR, as well as DFT calculations.

A selective electrochemical method of glycosylation of 3β-hydroxy-Δ5-steroids

A new electrochemical glycosylation method is presented. According to the method cholesterol and other 3beta-hydroxy-Delta(5)-steroids can be selectively transformed to glycosides using non-activated sugars. The method is also useful for the synthesis of glycoconjugates with sugar linked to a steroid moiety by an ether bond.

On reactions of steroidal 23-oxo and 23,24-epoxysapogenins with Lewis acids

The reaction of 23-oxotigogenin acetate with TMSOTf in THF afforded the corresponding bisnorcholanic lactone in 60% yield. The analogous reactions carried out in dichloromethane or benzene gave the rearranged products--the isomeric spirostanic ketone (10-15%) and bisfuran (40-42%). Similar products were also obtained upon treatment of 23,24-epoxysapogenins with BF(3). The epoxides treated with TiCl(4) afforded mostly chlorohydrins and no rearranged products were detected.

1H and13C NMR spectral analysis of (E)-asarone and its isomers

1H and 13C NMR data for six [(E)‐1‐propenyl]trimethoxybenzene isomers are reported. Spectral assignments were made on the basis of chemical shifts, 1H,1H coupling constants and two‐dimensional heteronuclear 1H,13C correlation techniques (HETCOR, COLOC). Copyright

Synthesis of Aromatic Retinoids and Curcuminoids and Evaluation of their Antiproliferative, Antiradical, and Anti-inflammatory Activities.

Abstract Natural retinoids and curcuminoids are known for their broad spectrum of biological properties, such as antioxidant, anti‐inflammatory, antitumor, and so forth. In this work, a convenient synthesis of aromatic retinoids and curcuminoids from vinyl or allyl ketones, and the corresponding alcohols, using olefin metathesis as a key reaction, was elaborated. The best yields and diastereoselectivities were obtained from allylic or homoallylic alcohols by employing the two‐step cross‐metathesis/oxidation procedure. The synthesized analogues were tested for their antiproliferative activity on human cancer cell lines of various origin (leukemia CEM, adenocarcinoma MCF7, cervical carcinoma HeLa) as well as for their antioxidant and anti‐inflammatory activity in vitro. All examined derivatives exhibited strong anti‐inflammatory activity in vitro without affecting cell viability. They also showed strong cytotoxicity against leukemia cell line CEM, except for 18 and 35. The antioxidant activity of the tested compounds was rather weak.

Oxidation of Olefins with Benzeneseleninic Anhydride in the Presence of TMSOTf

A new oxidizing system for olefins, consisting of benzeneseleninic anhydride and trimethylsilyl triflate, was studied. The highly reactive benzeneseleninyl cation is presumably formed under these conditions. It has been shown that different products are formed with this species depending on the specific structure of olefin. The 1,1-disubstituted olefins afforded mostly α,β-unsaturated carbonyl compounds. The sterically encumbered tri- or tetrasubstituted olefins yielded 1,2- or 1,4-dihydroxylated products, presumably via four-membered cyclic intermediates.