Zenon Łotowski

SYNTHESIS OF DIMERIC STEROIDS AS COMPONENTS OF LIPID MEMBRANES

Abstract The synthesis of three dimeric steroids 1,2, and 3, as components of artificial lipid bilayer membranes, is described. Di(3β-hydroxyfurost-5-en-26-yl) (1) was obtained from diosgenin by reductive fission of a ring F, substitution of -OH by -l, and the Wurtz reaction. Two other dimers 2 and 3 were synthesised from the pregnanoic ester 10 by an “alkylation-reduction” procedure.

Electrochemical studies of blocking properties of solid supported tethered lipid membranes on gold

The insulating properties of self-assembled thiolipid monolayers and tethered lipid bilayers on polycrystalline gold electrodes were studied by means of cyclic voltammetry (CV). These films were formed by two-step self-assembly processes. Electrochemical measurements of the heterogeneous electron transfer rate constant of different redox couples such as potassium ferrocyanide (K(4)[Fe(CN)(6)]) and dopamine (DP) were used to examine the molecular integrity and structural defects and pinholes within the monolayers. We demonstrate by means of cyclic voltammetry that the bilayer lipid membranes tethered to the gold surface are blocking, stable, yet retaining their dynamic properties and can be used as a model of the cell membrane.

Spectroscopic and Electrochemical Studies of Bilayer Lipid Membranes Tethered to the Surface of Gold

This work presents the results of the structural characterization and blocking properties of thiolipid mono- and bilayers containing dipalmitoylphosphatidylethanolamine and cholesteryl moieties tethered to a gold electrode via suitable side-chain alkanethiol molecules. Various electrochemical and spectroscopic techniques were used to evaluate the organization, thickness, and stability of both the monolayers and bilayers on the surface of polycrystalline gold electrodes. Infrared absorbance-reflectance spectroscopy, surface-enhanced Raman spectroscopy, and Langmuir-Blodgett techniques were used to assess the molecular structure, intermolecular orientation, and fluidity of self-assembled thiolipid films on gold surface. Electrochemical measurements were used to examine the molecular integrity within the monolayers and bilayers. We demonstrate that the investigated bilayer lipid membranes attached to gold form well-blocking, well-oriented, fluid-like films that can be used in future investigations as a good model of cell membranes addressing numerous applications. ranging from the understanding of functioning of membrane integral proteins to the development of biomembrane-based sensing techniques.

Unusual electrochemical oxidation of cholesterol.

It has been found that cholesterol undergoes direct electrochemical oxidation on platinum electrode in dichloromethane. Voltammetric measurements show that the process is controlled by the rate of electron transfer and the height of the oxidation peak is linear vs. concentration of cholesterol. Preparative electrolysis with separated cathodic and anodic compartments afforded dicholesteryl ether in a relatively high material yield. Depending on electrolysis conditions (composition of supporting electrolyte and electrolytic cell construction) various by-products with a 3beta-chloro, 3beta-acetoxy, or 3beta-acetylamino group were obtained.

On reaction of enamides with acetyl nitrate

Abstract The reactions of four steroidal enamides with acetyl nitrate were studied. The nitronium ion attacks the terminal carbon atom of the enamide moiety. Further transformations of the unsaturated nitro derivative consist of an allylic oxidation or a Nef-type reaction.

Nitration of N-acetyl enamines with acetyl nitrate

Abstract N-acetyl enamines undergo nitration at the double bond. Products of further nitration and oxidation in an allylic position are also formed. Sterically unhindered enamide, N-acetyl-cholest-2-en-3-amine, yields oxadiazole, as one of the reaction products.

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.

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.

N-Alkylation of 17-azasteroids

N-Alkylation of 17-azasteroid lactams (16-oxo-17-azaandrost-5-en-3 beta-ol acetate 3 and its D-homo analog 4) was studied. It has been found that both lactams are readily alkylated with iodomethane or iodoethane. In contrast to this there was no reaction with 2-iodo-6-methylheptane due to the steric hindrance. 1,4-Addition of lactam to the conjugated systems was also studied. The addition to acrylonitrile proved to be easy compared to crotononitrile. However the efficient addition to the latter compound was also attained by using potassium t-butoxide as a base in t-butanol.

Studies on the synthesis of cholane derivatives containing a mercapto group and their dimers with disulfide spacers. Part 2. 3α-Mercapto-5β-cholane-7α,12α,24-triol and its C(3)-C(3) disulfide dimer

Two new sulfur-containing cholane derivatives were obtained from cholic acid: 3α-mercapto-5β-cholane-7α,12α,24-triol 2 and its C(3)–C(3′) disulfide dimer 3 as a potential supramolecular host.