Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• the CuAAC process to more challenging substrates. Using fluorophore- and cholesterol-derived azides, coupling with the triethylgermanyl alkyne delivered the expected products 26 and 27, respectively, in good yield, enabling possible downstream diversification of these functional molecules of relevance

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• . The synthesis of methyl 4,6-dimethyldodec-5-enoate allowed the correct assignment of structures and showed the (E)-configuration of the double bond for the major naturally occurring diastereomers. These acids occur in small amounts compared to the major glandular components, cholesterol, and 1-O

• (see, e.g., [1][2]). Comparative analysis of SGS through GC–MS has revealed an assortment of lipids (reviewed in [2]), such as cholesterol [3][4][5][6][7][8], carboxylic acids [4][5][7][8][9][10][11][12], alcohols [8], 1-O-monoalkylglycerols [6][8], and others [13]. Nitrogen-containing compounds

• various lipid classes including sterols, triacylglycerols, and common fatty acid methyl esters [15]. Mass spectrometric analysis of the lipid content of crotalines, mainly the Western Diamondback Rattlesnake (C. atrox), confirmed the presence of cholesterol [3][6][11][16], fatty acids [11], fatty amides

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• complex molecules, such as naproxen and cholesterol derivatives, demonstrated good functional group compatibility (Scheme 23a). In the same year, Wang and Huang group reported a similar approach using electrochemical methods to synthesize 3-selenylindoles via the cyclization of 2-ethynylanilines and

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• diazo precursor. To achieve this, cholesterol was first esterificated using 2-(4-methoxyphenyl)acetic acid and DCC. The resulting arylacetic ester 12 was then reacted with 4-acetamidobenzenesulfonyl azide (p-ABSA) and DBU in anhydrous acetonitrile to yield the diazo compound 13 in 22% yield. The carbene

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• secondary metabolites, filamentous fungi stand out as the most prolific producers of meroterpenoids [1][2][3]. Representative fungal meroterpenoids of medicinal importance include pyripyropene A, a cholesterol acyltransferase inhibitor [4]; fumagillin, an antimicrobial agent [5]; and mycophenolic acid, a

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• of acyl-CoA: cholesterol acyltransferase [4]. In this mini-review, we focus on the fungal meroterpenoids biosynthesis, especially terpenonid cyclizations and post-cyclization modifications, which mostly contribute to the skeletal diversity. Several terpenoid cyclases and αKG-dependent dioxygenases

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• synthetic and biological membranes and therefore to induce an increase of membrane permeability. However, the effect of cholesterol (CHOL) content in the membrane on the CD permeabilizing effect was not considered yet. Given that an increase in CHOL content reduces the membrane permeability, the aim of this

• content membrane increase. Keywords: cholesterol; cyclodextrins; liposome; membrane permeability; Introduction Cyclodextrins (CDs) are a family of cyclic oligosaccharides made of glucopyranose units connected by α-1,4-glycosidic bonds. They possess a cone-shaped molecular structure with a hydrophobic

• extraction demonstrated that some CDs displayed a higher affinity towards phospholipids such as α-CD for phosphatidylinositol (PI), phosphatidylserine (PS), and dipalmitoyl phosphatidylcholine (DPPC) [10][11], etc., while other CDs preferentially extracted cholesterol (CHOL) from membranes such as β-CD and

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• other neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. Due to their ability to extract cholesterol, treatment with CDs could reduce atherogenesis and atherosclerotic plaque size by solubilizing cholesterol crystals [9]. In addition, CDs can sequester cholesterol

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• -C6 nanoparticle formulation decreased upon incubation. Based on previous studies with breast cancer cell lines, it is comprehensible that anionic nanoparticles induce cell proliferation inhibition earlier than polycationic nanoparticles. The impact of anionic nanoparticles on free cholesterol level

• was shown to decrease after 24 hours in a cholesterol extraction assay from MCF-7 cells. Poly-β-CD-C6 nanoparticles, on the other hand, removed three times more cholesterol from cells in 48 hours than anionic CD nanoparticles. In addition to surface charges, the molecular weight, and number of

• our group, and detailed studies were carried out to elucidate the mechanism. Both the results of our studies and the literature emphasize that cyclodextrins show high affinity for lipid-based molecules such as cholesterol and phospholipids in biological membranes [50][55][56]. Furthermore, it was

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• of Science, Port Said University, 42522-Port Said, Egypt 10.3762/bjoc.19.9 Abstract Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3β-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates

• –517. Keywords: Appel reaction; azidolysis; cholesterol; crystal structure; Walden inversion; Introduction 3β-Hydroxycholest-5-ene (cholesterol) is a structural and physiologic amphipathic steroid in human and animals as well. Cholesterol is an essential component of the plasma membrane, where it

• acts as fluidity buffer, permeability switch, and consequently in cell signaling pathways. Physiologically, cholesterol is the substrate for the biosynthesis of steroidal hormones, vitamin D and bile acids [1][2]. Although cholesterol can adopt 256 stereoisomeric structures, biological significances

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• and cholesterol lowering properties, for example [10]. As reported by Liu et al. [19], saponins can show interesting interactions with hydrophobic organic compounds (HOC) and more precisely with polycyclic aromatic hydrocarbons (PAHs). For example, phenanthrene can be removed by saponins [20], by

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• on steroid, cucurbitacin, or simple tetracyclic triterpenoid scaffolds. Important scaffolds here are campesterol (1), β-sitosterol (2), cholesterol (3), cucurbitadienol (4), and dammarenediol-II (5). Not surprisingly, CYPs involved in the biosynthesis of essential sterols in plants are highly

• versatility of CYPs in plant triterpenoid and steroid metabolism (Figure 6). Diosgenin (13) is a specialised plant natural product with a unique 5,6-spiroketal moiety that serves as an inexpensive raw material for the industrial synthesis of steroidal drugs. Diosgenin (13) biosynthesis from cholesterol (3

• catalyse the initial C22,16 dihydroxylation of cholesterol (3) [35]; in contrast, the related CYP DzCYP90B71 was found to catalyse only the first hydroxylation at C22 [66]. This step is followed by a rate-limiting cyclisation step through unstable furostanol intermediate 14 that involves CYP-catalysed

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• region on chromosome 6 [172]. Chemically, pyripyropene (PP) analogs are meroterpenoids containing a fused pyridyl α-pyrone moiety and eight contiguous stereocenters [170]. Metabolically, PPPA non-covalently binds within the fifth transmembrane domain of acyl-coenzyme A (CoA):cholesterol acyltransferase

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• also been employed in modern medicine because of its antimicrobial [3], antiprotozoal [4], antiviral [5], and anti-inflammatory [6] activity, and it is used in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11]. Most interestingly

• [65]. Accordingly, the activity of these derivatives in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11] is worth to be tested, because the parent berberine is already employed as drug for these diseases. In summary, a new

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• challenging. In an effort to target LNPs composed of an ionizable cationic lipid (DLin-MC3-DMA), cholesterol, the phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG 2000) to particular cell types, as well as to generate

• lipid, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and PEG-lipid, each with an essential role in the design (Figure 1). These lipids promote the effective distribution of the LNP in vivo as well as aid in effective cargo release from the endosome [1][37]. To this end, we herein

• mixture of DLin-MC3-DMA, DSPC, cholesterol, and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG 2000). Lipids were first extruded and then complexed with negatively charged aptamers annealed with fluorescently tagged complementary DNA oligonucleotides (GP160:A-1 or CCR5:G-3) to

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• cholesterol 44 and histamine 45. Scientific literature [97] reports a three-step continuous synthesis of [6,6]-tert-butyl phenyl-C61-butyrate 47 based on tert-butyl 4-benzoylbutyrate hydrazone in a microstructured flow reactor that eliminates the need for stage-by-stage isolation of intermediate products and

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• transformation. Also, the substituent at C17 does not affect the KSH performance: steroids with C17 keto functionality (i.e., 2 and 3) or cholesterol-like side chains at C20 (i.e., 1) were all transformed efficiently to the corresponding 9,11-dihydroxylated products. 1H and 13C 1D and 2D (COSY, HSQ and HMBC) NMR

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• transformation for late-stage modification of complex natural products was explored, and as shown in Scheme 4, the protocol was tested with various natural-product-derived triazoles. Novel C2-triazolyl products 4a–c were synthesized in good yield of 61–70% from triazoles derived from thymol, cholesterol and

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• , Scheme 24), demonstrating the power of this method for LSF, especially given the biological activity and prevalence of steroids, such as cholesterol, progesterone and testosterone. Interestingly, under their conditions, 2-heptanone, 2-decanone and 2-dodecanone as the substrates gave in each case a

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• cholesterol acyltransferase (ACAT) inhibitors [35], insecticides, antimicrobial agents, and immunomodulators [36]. In the current study, beauverolide N (4) displayed weak antibiofilm activity against S. aureus DSM1104 (MIC 250 μg/mL) and weak cytotoxicity against KB3.1 cells (IC50 16 μg/mL), while

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• functional roles, which range from widely distributed metabolites like cholesterol, to those with more restricted distribution like vitamins A and D, carotenoids, and steroid hormones, to some with highly restricted distribution like pheromones, fragrances, and defense metabolites [2][3]. Many of the more

• chemical diversity. The biosynthetic promiscuity is not a result of intrinsic "sloppiness" of terpenoid biosynthetic pathways, as terpenes that are classified as primary metabolites, such as cholesterol, are produced with high fidelity [40]. In contrast, more promiscuous terpene pathways might only be a