Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• either totally lipophilic (e.g., cholesterol) or amphipathic when possessing both polar and nonpolar groups (e.g., cholic acid). As shown in Figure 1, members of this family can be found in both plant and animal kingdoms, where they exert an amazing array of cellular functions such as structural and

• aldehyde and an enol functionality, which was subsequently reacted with isocyanide 31 – derived from cholesterol – and 3,5-dimethoxyaniline leading to the steroid–tetrahydropyridine hybrid 32 in good yield and excellent diastereoselectivity. As previously proven by the authors in their synthetic program on

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• Elias Christoforides Andreas Papaioannou Kostas Bethanis Department of Biotechnology, Agricultural University of Athens, 75 Iera Odos, Athens 11855, Greece 10.3762/bjoc.14.69 Abstract The role of beta-cyclodextrin (β-CD) in cholesterol removal primarily from mammalian cells and secondly from

• dairy products has been studied thoroughly in recent years. Although the physicochemical characterization of the inclusion compound of cholesterol in β-CD has been achieved by various methods, no crystal structure has been determined so far. We report here the crystal structure of the inclusion compound

• of cholesterol in β-CD. The inclusion complex crystallizes in the triclinic space group P1 forming head-to-head dimers which are stacked along the c-axis. One well-defined cholesterol molecule ‘axially’ encapsulated inside the β-CD dimer and 22 water molecules that stabilize the complexes in the

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• Fabio Tonin Isabel W. C. E. Arends Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands 10.3762/bjoc.14.33 Abstract Ursodeoxycholic acid (UDCA) is a pharmaceutical ingredient widely used in clinics. As bile acid it solubilizes cholesterol

• published in the 90’s, UDCA solubilizes cholesterol gallstones [2][3], it improves the liver function in cholestatic diseases [4][5][6][7][8] and it significantly decreases cholesterol saturation in the bile [8][9][10]. In terms of pharmacology, it is considered to be better than chenodeoxycholic acid (CDCA

• biosynthesis takes place in the liver starting from cholesterol: 17 enzymes are involved in the production of these molecules. The final products are the so-called primary bile acids: CDCA and CA [23]. Subsequently, these bile acids can be modified by intestinal bacteria to form the secondary bile acids as

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• the 3’-end of the sense strand to prepare cholesterol-conjugated siRNAs that were efficiently delivered to rat oligodendrocytes in vivo and achieved significant specific gene knockdown in these cells (Scheme 4A) [19]. The comparison with a non-cleavable alkyl linker suggests that a lipophilic siRNA

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• alcohol, 1-adamantanemethanol (2i) produced the desired glucoside 5i in 75% yield and moderate selectivity (Table 2, entry 8). Further, reactions with hindered acceptors, for instance, 1-adamantanol (2j), (+)-menthol (2k), (–)-menthol (2l), cholesterol (2m) required longer reaction times with high

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• reduces its potential medicinal applications. The targeted delivery of hydrophobic drugs can be achieved using liposome-based carriers. Therefore, we designed a traceable liposomal drug delivery system for trilobolide. The fluorescent green-emitting dye BODIPY, cholesterol and trilobolide were used to

• describe the synthesis and application of a fluorescent construct (further called construct 6, depicted in Scheme 1) based on a green-emitting BODIPY dye and trilobolide–cholesterol (Tb-ChL) in a liposome formulation. Trilobolide (Tb, Figure 1) is a potent natural compound of the sesquiterpene lactone

• green-emitting BODIPY, induced a dose-dependent NO production in primary rat macrophages. The potency of the fluorescent Tb to express inducible NO and cytokine secretion was shifted to a low micromolar range in comparison to the submicromolar activity of Tb itself. The introduction of cholesterol (ChL

Correlation of surface pressure and hue of planarizable push–pull chromophores at the air/water interface

• Frederik Neuhaus,
• Fabio Zobi,
• Gerald Brezesinski,
• Marta Dal Molin,
• Stefan Matile and
• Andreas Zumbuehl

Beilstein J. Org. Chem. 2017, 13, 1099–1105, doi:10.3762/bjoc.13.109

• values as before depicting a stably organized monolayer film with possible long-range order. The area per molecule of about 38 Å2 is comparable to that observed for cholesterol monolayers [21][22]. Simulation The molecular geometry of the mechanosensitive flipper probe was simulated in the gas phase at

• is a structural similarity between the flipper probes and cholesterol with both molecules being amphiphilic and flat. This called for a closer look at the influence of both molecules on phospholipid membrane organization (see Figure 4). For DPPC, the first-order phase transition between the

• disordered LE and the ordered LC phase can be identified as a plateau region in which the two phases are coexisting. The phase transition pressure amounts to ≈10 mN/m. Cholesterol has a fully condensed isotherm with low compressibility of the layer. The addition of flipper probes to DPPC does not influence

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• of important cellular functions, including pH-control [17][18], membrane trafficking, protein degradation, release of neurotransmitters [18], urinary acidification [19], bone resorption [20], sperm maturation [21], cholesterol biosynthesis [22] and cytokine secretion [23]. In recent years, a key role

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• Abstract Compared to cholesterol, hydroxycholesterols contain an additional hydroxy group in the alkyl chain and are able to efficiently cross the brain–blood barrier. Therefore, they are responsible for the sterol transfer between brain and circulation. The current study compares the membrane properties

• of several hydroxycholesterols with those of cholesterol using 2H NMR spectroscopy, a membrane permeability assay, and fluorescence microscopy experiments. It is shown that hydroxycholesterols do not exert the unique impact on membrane properties characteristic for cholesterol with regard to the

• influence on lipid chain order, membrane permeability and formation of lateral domains. Keywords: cholesterol; fluorescence; hydroxycholesterol; membrane structure; NMR; Introduction Cholesterol is a major component of mammalian cell membranes with various biological functions. It plays a key role in

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• )anthraquinones can be useful for non-covalent binding of lipids (such as cholesterol) or other lipophilic compounds. Results and Discussion Synthesis of bile acid derived ligands A series of different 24-aminocholanols (compounds 3a–c) was synthesized by reduction of the corresponding bile acid amides with

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• Niemann–Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β

• synthesize a novel multi-lactose-appended β-CD (multi-Lac-β-CD) and to evaluate its cholesterol-lowering effect in U18666A-treated HepG2 (NPC-like HepG2) cells. Further, the study aimed at delivering β-CD to hepatocytes via cholesterol-accumulated HepG2 cells, and indicated that the newly synthesized multi

• -Lac-β-CD had an average degree of substitution of lactose (DSL) of 5.6. This newly synthesized multi-Lac-β-CD was found to significantly decrease the concentration of intracellular cholesterol with negligible cytotoxicity as compared to HP-β-CD. An increased internalization of TRITC-multi-Lac-β-CD

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• topics including cholesterol manipulation, treatment of Alzheimer’s disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been

• their hemolytic activities. Indeed, several in vitro studies reported erythrocyte lysis although the toxicological implication in vivo is negligible. The lysis mechanism is related to their capacity to draw phospholipids and cholesterol out of the biological membrane (see below). Based on this, the

• view, they can be divided into eight categories: fatty acids (and their derivatives: mono-, di- and triglycerides and phospholipids), acylglycerols, phosphoglycerides, sphingolipids, glycolipids and polyketides, which result from the condensation of ketoacyl groups, sterols (e.g., cholesterol) and

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• complexation. In that way, it was possible to decorate CDVs with carbohydrates [32][33], with peptides [34], and also with DNA [35]. Moreover CDVs were also shown to form very dense membranes in combination with phospholipids and cholesterol [36]. Previous studies also showed promising results for PDT

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• versatility of the methodology we selected a set of representative molecules of different categories (Figure 1) such as pharmaceuticals (salicylic acid (2), paracetamol (7) and salbutamol (9)), cosmetic ingredients (cytronellol (6) and myrtenol (10)), biomolecules (cholesterol (3), N-Boc- tyrosine methyl

• had a low solubility in acetic anhydride as in the case of cholesterol, N-Boc-tyrosine methyl ester and salbutamol (entries 3, 8 and 9, Table 2). Comparing to data reported in the literature [42][43], the modest yields of peracetylated product obtained in case of cholesterol 3 and salbutamol 9 were

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• explore the structural diversity using different p-nitrophenyl carbonates which were prepared by treating an alcohol with p-nitrophenyl chloroformate in CH2Cl2 using pyridine as a base. Thus, homopropargyl alcohol, decanol, cholesterol and N-Boc-trans-4-hydroxy-L-proline methyl ester gave the

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• of luciferin yields the peroxy compound 1,2-dioxetane. This four-membered peroxide cycle is unstable and spontaneously decays to carbon dioxide and excited ketones, which release excess energy through light emission (bioluminescence) [62][63][64][65]. The in vivo oxidation of cholesterol by singlet

• oxygen produces the hydroperoxide cholesterol-5α-OOH, which undergoes a Hock oxidation to form atheronal A. The latter possesses proatherogenic effects and triggers the development of cardiovascular diseases [66][67][68][69][70][71]. The development of the chemistry of organic peroxides is closely

• model of the in vivo oxidation of cholesterol (219) by singlet oxygen produces cholesterol-5α-OOH 220, which is subjected to a Hock reaction to form the aldolization product 221 and keto aldehyde (atheronal A, 222) (Scheme 64) [67]. Keto aldehyde (atheronal A, 222) exhibits proatherogenic activity and

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• -reduction of an α,β-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-β-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent β-lactamic cholesterol absorption inhibitor. Keywords: β-lactam; ezetimibe; reductive

• . Finally the method is applied for the new synthesis of ezetimibe, a potent β-lactamic cholesterol absorption inhibitor. Results and Discussion First of all, we tried to solve the drawbacks of the previously reported method and found that changing the catalyst to [RhCl(cod)]2 greatly improved the reaction

• α,β-unsaturated lactone 2h, the β-lactam anti-3Ah that has a hydroxy group on the side chain was obtained in a low yield (Table 1, entry 11). This result was of interest because the reaction is applicable to the synthesis of ezetimibe. Ezetimibe is an inhibitor of the cholesterol transporter Niemann

Biradical vs singlet oxygen photogeneration in suprofen–cholesterol systems

• Fabrizio Palumbo,
• Francisco Bosca,
• Isabel M. Morera,
• Inmaculada Andreu and
• Miguel A. Miranda

Beilstein J. Org. Chem. 2016, 12, 1196–1202, doi:10.3762/bjoc.12.115

• i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia, Spain 10.3762/bjoc.12.115 Abstract Cholesterol (Ch) is an important lipidic building block and a target for oxidative degradation, which can be induced via free radicals or singlet oxygen (1O2). Suprofen (SP) is a

• membranes, cholesterol (Ch) is the most important lipidic building block. It is required for permeability, fluidity, and integrity of all animal cell membranes. However, as an unsaturated lipid, Ch is susceptible to oxidative degradation, which can result in potentially pathologic consequences encompassing

• the two competing mechanistic pathways. Experimental General Suprofen and β-cholesterol were commercially available. Solvents and other reagents were used as received from the supplier without additional purification. 1H NMR and 13C NMR spectra were recorded in CDCl3 as solvent on a Bruker AC-300 at

Superstructures with cyclodextrins: chemistry and applications III

• Gerhard Wenz and
• Eric Monflier

Beilstein J. Org. Chem. 2016, 12, 937–938, doi:10.3762/bjoc.12.91

• therapy [1]. Furthermore, it was found that lactose-appended β-CD lowers the cholesterol level in HepG2 cells – a result that is relevant for the treatment of Niemann–Pick-type C disease [2]. Metal-organic frameworks (MOFs) created from native CDs can be applied for the separation of isomeric xylenes or

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• direct assemblies, the structural definition and kinetic stability of 2:1 host–guest complexes might be low. We therefore wanted to introduce a bias by using very rigid guests. We were therefore grateful to discover that a range of steroids, from as small as estradiol to as large as cholesterol formed

• , e.g., cholesterol, NMR showed that the capsular complex was near its carrying capacity, but the complex was still stable on the NMR timescale. It transpires that any molecule that would energetically rather not be in water and is small enough to fit, forms a capsular complex with octa-acid. There are

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• formation yielding in the α-pyrone moiety can be accomplished in different ways. The different biosynthetic routes towards an α-pyrone ring will be presented. The biosynthetic mechanisms to yield saturated lactones, like the statin drug lovastatin, which is in application for lowering cholesterol, will not

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• binding affinity [21], inhibition of hepatic cholesterol [22], inhibition of aldose reductase [23], antiproliferative [24], antiviral, cytotoxic [25], antifungal [26], anti-HIV [27][28][29] and antibacterial activity [30]. Although rare, there are a few natural products, for example, melanervin (5), a

Thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) and complexation with β-cyclodextrin

• Daniel I. Hădărugă,
• Mustafa Ünlüsayin,
• Alexandra T. Gruia,
• Cristina Birău (Mitroi),
• Gerlinde Rusu and
• Nicoleta G. Hădărugă

Beilstein J. Org. Chem. 2016, 12, 179–191, doi:10.3762/bjoc.12.20

• –2.2 g/100 g of salmon [9][12]. The health benefit of omega-3 FAs (but especially EPA, (all-Z)-5,8,11,14,17-eicosapentaenoic acid and DHA, (all-Z)-docosa-4,7,10,13,16,19-hexaenoic acid) in reducing cardiovascular risk by reducing blood lipids (mainly LDL cholesterol and triglycerides), is well known

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• , grapefruit and orange. Several reports on biological effects of hesperetin and naringenin have been found [6], including blood lipid- and cholesterol-lowering effects [7][8][9], anti-inflammatory [10][11][12][13] and anticancer [14][15][16] activities, improved microcirculation, recovery of venous ulcers

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• and promoted a new dynamic view on biosynthesis research [4], leading to numerous breakthroughs such as the discovery of cholesterol biosynthesis [5]. With the rise of NMR and MS methods the usage of radioactive nuclei such as 14C and 3H shifted towards stable isotopes such as 13C and 2H [6], with the