Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• to the inhibition of FAT [10]. In search for further chemical entities that can control resistant weed species via the inhibition of FAT, we were interested in exploring a compound class containing a 1,8-naphthyridine core that was first reported by BASF, e.g., compound 4 [11]. In contrast to

• bicyclic cinmethylin (1) and methiozolin (2), substituted 1,8-naphthyridine 4 does not contain any stereocenters but still displays promising efficacy against grass weeds. Further considering the rather low molecular weight (220 g/mol) and structural simplicity, compound 4 is a highly attractive initial

• lead structure with ample space for structural variations. By formally replacing one pyridine moiety of 1,8-naphthyridine 4 by a five-membered thiazole unit, we have identified thiazolo[4,5-b]pyridine 5 as a strong inhibitor of acyl-ACP thioesterase, which has further been confirmed via an X-ray co

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• ; isoquinolino[1,2-f][1,6]naphthyridine; Introduction Among various well-known cycloaddition reactions such as the 1,3-dipolar cycloaddition reaction, Diels–Alder reaction, and the Povarov reaction, the cycloaddition reaction of Huisgen 1,4-dipoles with activated alkenes received increasing attention [1][2][3

• Povarov reaction of 3-aminocoumarins, aldehydes, and 5,6-unsubstituted 1,4-dihydropyridine derivatives for the construction of exo-hexahydrochromeno[3,4-h][1,6]naphthyridine-3-carboxylate derivatives (reaction 3 in Scheme 1) [44]. In these reactions, the 5,6-unsubstituted 1,4-dihydropyridines usually

• ]naphthyridine and 2-azabicyclo[4.2.0]octa-3,7-diene derivatives. Results and Discussion Initially, the reaction conditions were briefly examined by using isoquinoline (1), dimethyl acetylenedicarboxylate (DMAD, 2) and 5,6-unsubstituted 1,4-dihydropyridine 3 as standard reaction (Table 1). The three-component

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• ]naphthyridine motifs 188 as desired products. Based on the experimental results and annulation chemistry a catalytic mechanism has been proposed (Scheme 36b) that involves the C3 hydrogen of pyridine undergoing a cyclorhodation with the catalyst in the presence of NaOAc, directed by in-built NHC ligand

• 205 were accessed in moderate to excellent yields and also naphthyridine derivatives (205k and 205l) were synthesized. In the proposed mechanism, the initial deprotonation of HNBn2 by Ln[N(TMS)2]3 provided the lanthanide amide. Activation of the vinyl-substituted pyridin-3-amine 204 by the lanthanide

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

• physiological conditions, development of novel nucleobases for Hoogsteen recognition of A has attracted less attention than the problem of C protonation discussed above. Similar to K, 7-Cl-bT, a substituted naphthyridine derivative (Figure 6), forms stronger Watson–Crick base pairs and Hoogsteen triplets with A

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• tetrahydronaphthyridines predominantly revolve around late-stage hydrogenation of fully aromatic 1,8-naphthyridine derivatives 3, usually prepared via an acid or base-catalysed Friedländer reaction between 2-aminonicotinaldehyde (1) and the corresponding ketone 2 (Scheme 1). Both reactions employ harsh conditions with

• , GlaxoSmithKline disclosed a route to a fluoropyrrolidine 6 using a Wittig reaction between phosphonium salt 4 and aldehyde 5 [2]. The synthesis of phosphonium salt 4 (itself requiring 6 steps including partial saturation of a 1,8-naphthyridine moiety) and the formation of the triphenylphosphine oxide byproduct in

• -1,8-naphthyridine analogues. The investigation initially began using commercially available N-Boc-protected tetrahydro-1,8-naphthyridine 8 [16]. Upon deprotonation and quenching with diethyl chlorophosphate, migration of the Boc group from the nitrogen atom to the exocyclic methyl group was observed

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• Benedikt C. Melzer Alois Plodek Franz Bracher Department of Pharmacy – Center for Drug Research, Ludwig-Maximilians University Munich, Butenandtstr. 5–13, 81377 Munich, Germany 10.3762/bjoc.15.222 Abstract Readily available 4-bromobenzo[c][2,7]naphthyridine undergoes regioselective direct ring

• -mn]acridones has been worked out. Keywords: alkaloids; cyclization; metalation; naphthyridine; pyridoacridine; Introduction Polycyclic aromatic alkaloids are a unique class of natural products with a broad pattern of biological activities. One of the most prominent classes are the so-called

• common structural feature of the abovementioned alkaloids is the benzo[c][2,7]naphthyridine ring system, as exemplified by the marine alkaloids amphimedine (1), ascididemin (2), kuanoniamine A (3), styelsamine D (4), and eilatin (5). Skyler and Heathcock described, based on the occurrence and proposed

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• , Florida 32611, USA 10.3762/bjoc.14.175 Abstract Chiral bisoxazoline ligands containing naphthyridine, pyridazine, pyrazole, and phenol bridging units were prepared and shown to form bimetallic complexes with various metal salts. X-ray crystal structures of bis-nickel naphthyridine-bridged, bis-zinc

• was reported to form a bis-palladium complex with one equivalent of [(η3-C3H3)PdCl]2 [51]. Little is known about the complexing abilities of compounds 9 and 11 [49][52]. The naphthyridine-based ligand 10 forms a dinuclear complex with nickel(ΙΙ) acetate (Ni∙∙∙Ni distance = 3.132 Å). Compound 12

• available. This led to the selection of naphthyridine, pyridazine, pyrazole, and phenol building blocks. We opted to connect these linkers to oxazolines via amide bonds. The reasoning for this was twofold. Firstly, this should provide ligands with significantly improved stabilities over for instance imine

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• diphosphorylated products [95]. The 1,5-naphthyridine 274 and phenanthrolines 276, 278 and 280 in the presence of more than 2 equiv of DMPTMS were converted to the corresponding diphosphorylated products 275, 277, 279 and 281 with a high diastereoisomeric ratio (Scheme 57). In this reaction, the 1,4-addition of

Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• [1][2][3][4][5][6][7][8][9][10][11][12]. A number of transition metal complexes of NHCs containing pyridine [13], pyrimidine [14], pyrazole [15][16], naphthyridine [17], pyridazine [18], and phenanthroline [19][20] donating groups have been studied in metal-catalyzed organic transformations. Recently

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• . Box 35, FI-40014, Jyväskylä, Finland 10.3762/bjoc.11.227 Abstract The association of substituted benzoates and naphthyridine dianions was used to study the complexation of dibutyltriuret. The title molecule is the simplest molecule able to form two intramolecular hydrogen bonds. The naphthyridine

• benzoates 2–9 and ditetrabutylammonium 1,8-naphthyridin-2,7-diolate (10) (Figure 1). The benzoate anions forming two hydrogen bonds [10] were chosen in order to obtain a series of anions with tuneable HB acceptor properties, while the naphthyridine derivative was used to test if the dibutyltriuret is able

• such effect is possible in other form∙∙∙benzoate complexes. This suggests that said alternate 1e∙∙∙benzoate binding may be present and that NO2 group has higher anisotropic influence on CH2 shift than -CO2– one. Association of 1 with naphthyridine dianion 10 The Kassoc equal to 300 M−1 for 1∙∙∙10

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• and benzo[b]indolo[1,2-h]naphthyridine heterocycles in one-pot, multi-step cascade sequences [3]. These ring systems are not only of chemical interest but biological testing revealed promising in vitro antiplasmodial activity and anticancer activity in certain cases [3]. While the analogous base

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• reaction to yield 5-aryl-3,4-dihydro-1,8-naphthyridin-2(1H)-ones by an efficient synthetic route. Keywords: inverse-electron-demand Diels–Alder reaction; microwave irradiation; naphthyridin-2(1H)-ones; Sonogashira cross-coupling; 1,2,4-triazine; Introduction 1,8-Naphthyridine derivatives are an important

Azobenzene dye-coupled quadruply hydrogen-bonding modules as colorimetric indicators for supramolecular interactions

• Yagang Zhang and
• Steven C. Zimmerman

Beilstein J. Org. Chem. 2012, 8, 486–495, doi:10.3762/bjoc.8.55

• Yagang Zhang Steven C. Zimmerman Department of Chemistry, 600 South Mathews Avenue, University of Illinois, Urbana, IL 61801, USA 10.3762/bjoc.8.55 Abstract The facile coupling of azobenzene dyes to the quadruply hydrogen-bonding modules 2,7-diamido-1,8-naphthyridine (DAN) and 7-deazaguanine urea

• -diamido-1,8-naphthyridine (DAN); polymer; quadruply hydrogen bonding; supramolecular; Introduction Lehn’s pioneering studies [1] have advanced supramolecular chemistry to the point where complex hierarchical self-assembled [2] and even dynamically assembled structures are routinely described [3

• -bromobutyrate to give 2 in 72% yield [47]. Acid-catalyzed deprotection of 2 afforded carboxylic acid 3 in 85% yield [48]. The coupling of 3 with the mono-heptanamide of 2,7-diamino-1,8-naphthyridine (DAN 4) was effected by using a standard peptide-coupling method. Thus, 1-(3-dimethylaminopropyl)-3