Electrochemical oxidation of cholesterol

Indirect cholesterol electrochemical oxidation in the presence of various mediators leads to electrophilic addition to the double bond, oxidation at the allylic position, oxidation of the hydroxy group, or functionalization of the side chain. Recent studies have proven that direct electrochemical oxidation of cholesterol is also possible and affords different products depending on the reaction conditions

Two-step Synthesis of Solasodine Pivalate from Diosgenin Pivalate

A two-step synthesis of solasodine pivalate from diosgenin pivalate is described. The key transformation involves the reaction of diosgenin pivalate with benzyl carbamate (CbzNH2) promoted by TMSOTf. During the reaction the F-ring of the spiroketal moiety opens up with a simultaneous introduction of a Cbz-protected amino group in position 26. A one-pot deprotection of 26-amine with AcBr/BuOH followed by the N-cyclization affords solasodine pivalate in 45% overall yield

Synthesis of Demissidine Analogues from Tigogenin via Imine Intermediates

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO4 oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

3α,5α-Cyclocholestan-6β-yl alkyl and aryl ethers were proved to be efficient cholesteryl donors in the electrochemical synthesis of glycoconjugates. 3α,5α-Cyclocholestan-6β-ol (i-cholesterol) and its tert-butyldimethylsilyl ether can also be used for this purpose. The i-cholesterol derivatives show similar reactivities to those of previously studied 3α,5α-cyclocholestan-6β-thioethers

Synthesis of 25-Hydroxy-provitamin D₃ by Direct Hydroxylation of Protected 7‑Dehydrocholesterol

A new synthetic route to 25-hydroxy-provitamin D3 was elaborated. The synthesis consists of direct hydroxylation at C-25 of 7-dehydrocholesterol hetero Diels–Alder adducts. The adducts were prepared by [4 + 2] cycloaddition of azadienophiles to the steroidal diene. The hydroxylation reactions of adducts were carried out with different dioxiranes or with chromyl trifluoroacetate. The byproducts of these reactions were isolated and identified. The strengths and weaknesses of hydroxylation methods with different oxidizing agents were discussed

A Study on the Chemistry and Biological Activity of 26-Sulfur Analogs of Diosgenin: Synthesis of 26-Thiodiosgenin S-Mono- and Dioxides, and Their Alkyl Derivatives

A chemoselective procedure for MCPBA oxidation of 26-thiodiosgenin to corresponding sulfoxides and sulfone was elaborated. An unusual equilibration of sulfoxides in solution was observed. Moreover, α-alkylation of sulfoxide and sulfone was investigated. Finally, the biological activity of obtained compounds was examined

Synthesis of New Cisplatin Derivatives from Bile Acids

A series of bile acid derived 1,2- and 1,3-diamines as well as their platinum(II) complexes were designed and synthesized in hope to get a highly cytotoxic compound by the combination of two bioactive moieties. All complexes obtained were subjected to cytotoxicity assays in vitro and some hybrid molecules showed an expected activity

Syntéza a cholinesterázová inhibiční aktivita analogů solasodinu se sedmičlenným F kruhem

Solasodine analogues containing a seven-membered F ring with a nitrogen atom placed at position 22a were prepared from diosgenin or tigogenin in a four-step synthesis comprising of the simultaneous opening of the F-ring and introduction of cyanide in position 22 alpha, activation of the 26-hydroxyl group as mesylate, nitrile reduction, and N-cyclization. Solasodine, six obtained 22a(N)-homo analogues, as well as four 26a-homosolasodine derivatives and their open-chain precursors (13 in total) were tested as potential inhibitors of acetyland butyryl-cholinesterases and showed activity at micromolar concentrations. The structure-activity relationship study revealed that activities against studied esterases are affected by the structure of E/F rings and the substitution pattern of ring A. The most potent compound 8 acted as non-competitive inhibitors and exerted IC50 = 8.51 mu M and 7.05 mu M for eeAChE and eqBChE, respectively. Molecular docking studies revealed the hydrogen bond interaction of 8 with S293 of AChE; further rings are stabilized via hydrophobic interaction (ring A) or interaction with Y341 and W286 (rings B and C). Biological experiments showed no neurotoxicity of differentiated SH-SY5Y cells. More importantly, results from neuroprotective assay based on glutamate-induced cytotoxicity revealed that most derivatives had the ability to increase the viability of differentiated SH-SY5Y cells in comparison to galantamine and lipoic acid assayed as standards. The newly synthesized solasodine analogues are able to inhibit and to bind cholinesterases in noncompetitive mode of inhibition and exhibited neuroprotection potential of differentiated neuroblastoma cells after Glu-induced toxicity.Analogy solasodinu obsahující sedmičlenný kruh F s atomem dusíku umístěným v poloze 22a byly připraveny z diosgeninu nebo tigogeninu čtyřstupňovou syntézou zahrnující současné otevření F-kruhu a zavedení kyanidu do polohy 22 alfa, aktivaci 26-hydroxylová skupina jako mesylát, redukce nitrilu a N-cyklizace. Solasodin, šest získaných 22a(N)-homo analogů, stejně jako čtyři deriváty 26a-homosolasodinu a jejich prekurzory s otevřeným řetězcem (celkem 13) byly testovány jako potenciální inhibitory acetyl a butyryl-cholinesteráz a vykazovaly aktivitu při mikromolárních koncentracích. Studie vztahu struktura-aktivita odhalila, že aktivity proti studovaným esterázám jsou ovlivněny strukturou E/F kruhů a substitučním vzorem kruhu A. Nejúčinnější sloučenina 8 působila jako nekompetitivní inhibitory a vykazovala IC50 = 8,51 uM a 7,05 mu M pro eeACHE a eqBChE, v daném pořadí. Studie molekulárního dokování odhalily interakci vodíkové vazby 8 s S293 z AChE; další kruhy jsou stabilizovány hydrofobní interakcí (kruh A) nebo interakcí s Y341 a W286 (kruhy B a C). Biologické experimenty neprokázaly žádnou neurotoxicitu diferencovaných buněk SH-SY5Y. Ještě důležitější je, že výsledky neuroprotektivního testu založeného na cytotoxicitě indukované glutamátem odhalily, že většina derivátů měla schopnost zvýšit životaschopnost diferencovaných buněk SH-SY5Y ve srovnání s galantaminem a kyselinou lipoovou testovanými jako standardy. Nově syntetizované analogy solasodinu jsou schopny inhibovat a vázat cholinesterázy nekompetitivním způsobem inhibice a vykazují neuroprotektivní potenciál diferencovaných neuroblastomových buněk po toxicitě indukované Glu