Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• cascade [45], and base-promoted annulations with isatoic anhydrides [46]. Many other contributions in this field up to 2019 have been extensively reviewed [47][48][49], with special attention to the total synthesis and functional analysis of 2-alkyl-4-quinolones as microbial signaling molecules [50][51

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• ]. Natural products that are structurally related to 1–6 were discovered in Pseudomonas aeruginosa. It was shown that these compounds function as signaling molecules involved in quorum sensing and stress response [24] which might be an explanation for their low bioactivity against the tested bacteria. Upon

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• responsible for the modification of many important signaling molecules that are involved in a wide variety of crucial biological processes, such as cellular respiration, detoxification, and photosynthesis, within almost all living organisms [8]. In general, Ptases can be distinguished by their substrate

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• be detected when comparing similar glycomes by this method. The articles by Groth et al. [12] and by Bagdonas et al. [13] illustrate how glycoinformation can be harvested and integrated from available -omics databases, with the former paper identifying putative cell signaling molecules and

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• recognition; peptide-based; Introduction Molecular recognition involving amino acids or peptides are important factors in biochemical and medicinal processes [1][2][3]. Amino acids work as biosynthetic building blocks or as signaling molecules. For example, the well-known neurotransmitters glutamate and γ

• a bound glutamate molecule [4]. Peptides often work as signaling molecules or hormones, such as small neuropetide endorphins, produced by the central nervous system to relieve stress or enhance pleasure. They produce signaling cascades in the brain by interacting with opiate receptors. Sometimes

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• . Though not alkylated, the close structural similarity to 3 suggests that 1 is also a member of the 2-alkyl-4-quinolone class signaling molecules/antibiotics known from Pseudomonas aeruginosa and some Burkholderia species [26][27]. Quinolones of this class are classified into two lineages, those with or

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• (HHQ, 1) are important signaling molecules involved in quorum sensing and as such play an important role in virulence regulation [3][10][11][12]. Another metabolite from the AQ biosynthesis pathway of P. aeruginosa is 2-heptyl-1-hydroxy-4(1H)-quinolone (generally referred to as 2-heptyl-4

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• sensing and representative signaling molecules. Inhibitors of bacterial quorum sensing.

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• central regulator mechanism of virulence expression that contributes to the formation and maintenance of biofilms and tolerance to conventional antimicrobials. QS Signaling molecules (QSSMs) may be recognized and may function also within the host cells, being potentially involved in the progression of the

• infections. P. aeruginosa produce two types of quorum-sensing signaling molecules (QSSMs): N-acylhomoserine lactones (AHL) and 2-alkyl-4-quinolone (PQS) derivatives. The AHLs molecules described so far in P. aeruginosa belong at two quorum sensing (QS) systems: las and rhl systems whose autoinducer (AI

• ) molecules are N-(3-oxododecanoyl)homoserine lactone (OdDHL, 3-oxo-C12-HSL), and N-butyryl-L-homoserine lactone (C4-HSL), respectively. AHL systems are interconnected by a third mechanism that uses signaling molecules such as 2-alkyl-4-quinolone (AQ), the most relevant one being 3-hydroxy-4-quinolone (PQS

Lipids: fatty acids and derivatives, polyketides and isoprenoids

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2017, 13, 793–794, doi:10.3762/bjoc.13.78

• constituents, for energy storage, or as signaling molecules. If the human lipid metabolism is disturbed, this may lead to serious illnesses such as adipositas and its subsequent complications including cardiovascular diseases or diabetes mellitus. Other consequences of a disordered lipid metabolism include

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• because of a high proliferation rate. In the quorum sensing process, bacteria constitutively secrete specific extracellular signaling molecules, called quorum sensing pheromones, to gather information about their cell population density [15][16][17][18]. Various phenomena are stimulated by an increase in

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• as well as in the design of chemical probes to dissect glorin-mediated signaling pathways. Keywords: Dictyostelium; glorin; multicellularity; Polysphondylium; signaling molecules; social amoebae; Introduction The emergence of multicellularity from unicellular ancestors is considered a major

• form a multicellular organism. Eventually, they culminate in fruiting bodies to spread some of the population as dormant spores into the environment. Secondary metabolites often constitute the key signaling molecules in these developmental processes [3][4]. For instance, aggregation of the amoebae is

• initiated by pulses of chemoattractive, low-molecular weight signaling molecules – so-called acrasins [5]. Additionally, it has been shown that natural products are also involved in interspecies interactions of social amoebae and bacteria [6][7][8][9][10]. A detailed investigation of both inter- and

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• mode of action of 4 and structure–activity relationship studies are ongoing and results will be reported in due course. BHL and OdDHL are two natural AHL-based signaling molecules used by P. aeruginosain quorum sensing. PQS is a natural quinolone signaling molecule also used by P. aeruginosa in quorum

Biosynthesis of α-pyrones

• Till F. Schäberle

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

• ), represent widely exploited building blocks in synthetic chemistry. Examples are the syntheses of compounds like α-chymotrypsin, coumarins, pheromones, and solanopyrones [1]. Known biological functions reach from intermediates and end products in primary metabolism to signaling molecules and molecules which

• ], and recently it was reported that so called photopyrones (8–15) act as signaling molecules in the cell–cell communication system of the bacterium Photorhabdus luminescens (Figure 1) [14]. Since the biological activities of α-pyrones are very diverse, these compounds are in the focus of synthetic

• thioester bond is cleaved and subsequently lactonization takes place, yielding in the final product (Figure 24 B). In Photorhabdus luminescens it was shown that α-pyrones act as bacterial signaling molecules at low nanomolar concentrations [14]. A similar mechanism for the biosynthesis of these photopyrones

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• evolutionary-based refinement for at least a billion years [9][10][11]. They function as chemical modulators and signaling molecules for intra- and interkingdom interactions such as defense, protection, behavior, virulence, and central physiological functions; thereby generating evolutionary benefits for the

• occurrence of these metabolites in often subinhibitory concentrations indicates that they might not primarily function as antimicrobials. Rather they work as signaling molecules leading to modulation of gene expression in the target organism, to alteration in factors contributing to the virulence or

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• [5] and selective COX-2 inhibitors [6]. Recently, it was shown that photopyrones (Figure 1) are signaling molecules in a new cell–cell communication system in the entomopathogenic bacterium Photorhabdus luminescens. The system consists of endogenously produced photopyrones as signaling molecules and

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• activation, and direct activation signaling pathways, have been described [88]. First, the integrins and growth factors can activate independent signals to trigger the same signaling molecules as concomitant activation. It has been reported that the Ras-MAPK (mitogen-activated protein kinase) pathway

• an environment to help some growth factor receptors for their interaction with downstream signaling molecules [90]. These receptors include the epidermal growth factor receptor (EGFR), Met, platelet-derived growth factor receptor (PDGFR), insulin receptor, and vascular endothelial growth factor

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• either anti- or pro-angiogenic activity, which are embedded together with enzymes and signaling molecules (Table 1) into a very complex network of signaling pathways [3][4]. For example, in the case of cancer development, the growing tumor disturbs the angiogenic balance in tissue and induces the

• , the tumor cells express pro-angiogenic factors including growth factors such as the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and enzymes such as cyclooxygenase 2 (COX-2) and protein kinase A (PKA) as well as signaling molecules such as integrins. The evoked cascade

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• acids vary in their side-chain functionality and possess different polarities that are important for their biological function. Peptides can be biologically active hormones, neurotransmitters and neuropeptides, growth factors, signaling molecules and antibiotics. These diverse functions make peptides an

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• unigenomic spores [2]. Aerial hyphae production and sporulation is triggered by nutritional stress and is accompanied by the production of secondary metabolites. These specialised metabolites likely function both as chemical weapons against competing organisms in the soil and as signaling molecules to

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• microorganisms communicate (within a single bacterial species or between diverse species) and alter their gene expression through production of certain signaling molecules [3]. In this regard, the culturing of microbial communities or the co-culture of two specific microbial organisms has been successfully

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• Ephrin/Eph system in determining motor neuron susceptibility to degeneration in ALS. Ephrins and their cognate receptors (Eph) are important in nervous-system development where they assist with axonal pathfinding and repulsion. In adults these signaling molecules have been demonstrated to play essential

• neuroprotection is to inhibit the signaling molecules that antagonize cellular survival and promote neuron death in disease models. Glycogen synthase kinase-3 (GSK-3) is an essential signaling molecule involved in many cellular processes including glycogen metabolism, cell-cycle regulation, cellular proliferation

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro- 1,3-dihydroxy- 2-(octadecanoylamino)octadec- 4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

• Gergana S. Nikolova and
• Günter Haufe

Beilstein J. Org. Chem. 2008, 4, No. 12, doi:10.3762/bjoc.4.12

• diastereo- and enantioselective synthetic route was presented for the preparation of the first analogues 1b and 2b, fluorinated in 4-position, of the natural signaling molecules sphingosine (1a) and ceramide (2a) with the required D-erythro-configuration (2S,3S) of the stereogenic centers and a Z configured