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

• 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

• -crystal structure [12]. Additionally, greenhouse trials have shown that thiazolopyridine 5 and a large number of closely related analogues display excellent control of grass weed species in preemergence applications [13][14]. Independently, researchers at Syngenta have shown that the pyridine unit in the

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• as guest molecules. Here we report the co-crystal structures of phenol, which is solid at room temperature, with both 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane (TDA) and 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO). The co-crystals were obtained from solutions in dichloromethane by slow

• configuration [18]. One limitation of the EnOC method was that the guest compound to be encapsulated had to be a liquid, so that it could act as solvent for the TAA, which would rapidly crystallize upon cooling of a hot, saturated solution. Here we report two co-crystal structures of TAAs with phenol, obtained

• conventional approach, using dichloromethane as solvent and slow evaporation or diffusion of a poor solvent into the dichloromethane solution to obtain co-crystals. Two such solvent-based crystallization runs produced the co-crystal structures shown in Figure 2. For TDA, 5 mg of the chaperone and 1 mg of

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• be detected by its luminescence [77][78][79]. Overall, while crystal structures provide fantastic insight into molecular interactions of such supramolecular ligands, they do not necessarily reflect the binding situation in solution. Furthermore, to our knowledge no protein co-crystal structures with

• the number of methyl groups [29][49]. On the protein surface, both ligands showed a clear preference for the sterically most accessible dimethyl-lysine residue K34Me2 which is located in a solvent-accessible loop. Binding of cucurbit[7]uril to this residue was confirmed by the co-crystal structure of

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• this software a user uploads a glycan binding protein complexed to a carbohydrate fragment in PDB format. This need not be a co-crystal structure, and can be a modeled structure as well. The application then finds glycans that contain this fragment which are present on the CFG microarray data and

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• , encoded by the gene fusA1) as their target [11][12]. The co-crystal structure of argyrin B (2) and P. aeruginosa EF-G1 provides structural information of the complex at atomic resolution as basis for further structure-based optimization [11]. Jones and colleagues analyzed possible resistance mechanisms to

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• . employing substitutional disorder, achieved the co-crystallization of six components [28]. As for positional disorder, it generally indicates the same molecule or assembly can adopt more than one favourable conformation. From this perspective, disorder can be considered as a special case of a co-crystal or

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• -bond formation in supramolecular chemistry which occurs in solution-phase synthesis is almost impossible in solid-state reactions. However, MacGillivray’s group demonstrated several examples of co-crystal formation or supramolecular synthesis in the solid phase through mechano-milling or dry grinding

• ]-cycloaddition methodology. They used the vertex grinding technique where solid-state grinding and UV irradiation was done simultaneously [111] and verified co-crystal formation of a resorcinol derivative with dipyridylethylene in the solid state. Also, the supramolecular catalysis of [2 + 2] photodimerization

• [112]. In this work they have also demonstrated that metallic pnictogens do form sufficiently strong halogen bonds to enable co-crystal formation. Mal and co-workers have shown that a contact explosive, i.e., the mixture of primary amines and phenyliodine diacetate led to a high-yielding reaction at

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• also found that RU7 selectively disrupts the E. coli β-clamp without affecting its eukaryotic counterpart in Saccharomyces cerevisiae. In this same study, the co-crystal structure of RU7 with the sliding clamp revealed that the inhibitor occupies the deepest subsite (i.e., 1) of the two subsites that

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• -inducer binding site in complex with 36 was solved at 2.95 Å resolution (Figure 16), as well as a co-crystal structure of the native HHQ C9-congener NHQ [76] demonstrating a competitive binding mode. When compared to the native ligand NHQ, 36 shows similar hydrophobic interactions (Figure 16). In addition

• -inhibitors 24–26. PqsE co-crystal structures. (A) native product 2-ABA; (B–D) hit fragments 24–26. Structurally diverse PqsBC-inhibitors 27–30. Native PqsR ligand HHQ (31) which is converted

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• ) which were agitated using a membrane valve [80]. Within three minutes, almost complete disruption of Gram-positive bacteria was effected enabling downstream analysis by quantitative PCR. Associative processes Variable drug bioavailability associated with crystal and co-crystal polymorphism can be

• equimolar quantities of 9-methyladenine and 1-methylthymine in an amalgam mill gave powder diffraction patterns consistent with the formation of Hoogsteen-type base-pairing (Scheme 16) [81]. No co-crystal formation was observed using 1-methylcytosine with 9-ethylguanine or other combinations which did not

• -fluorouracil (5FU) and nucleoside analogue prodrugs subject to mechanochemical co-crystal or polymorph transformation. Nucleoside tritylation effected by hand grinding in a heated mortar and pestle. Persilylation of ribonucleoside hydroxy groups (and in situ acylation of cytidine) in a MBM. Nucleoside amine

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• other alternative energy inputs is still scarce. Only three examples highlight their peculiar role for metal-catalysed processes in a ball mill (Mirozoki–Heck reaction) [6], by ultrasound (copper-catalysed cyanation reaction) [7], and for co-crystal formation in the polymer-assisted grinding process

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• (−)-sparteine hydrobromide in chloroform was treated with racemic 1,2-dibromohexafluoropropane, a yellow co-crystal was isolated. The structure of the co-crystal was confirmed by single-crystal X-ray diffraction, and it showed that the co-crystal was made up from one molecule of (−)-sparteine hydrobromide and

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• ); His96 and p53 residue (yellow sticks, PDB-ID 1YCR) are included for reference. B) Co-crystal structure of MI63-analogue in MDM2 and redocked MI63-analogue (green sticks) superimposed on the key amino acid side chain residue of the p53/MDM2 (yellow sticks, PDB-ID: 1YCR). Synthesis of compounds 2

Donor–acceptor type co-crystals of arylthio-substituted tetrathiafulvalenes and fullerenes

• Xiaofeng Lu,
• Jibin Sun,
• Shangxi Zhang,
• Longfei Ma,
• Lei Liu,
• Hui Qi,
• Yongliang Shao and
• Xiangfeng Shao

Beilstein J. Org. Chem. 2015, 11, 1043–1051, doi:10.3762/bjoc.11.117

• and Discussion Synthesis and compositions On the basis of hundreds of experimental runs, we found that the Ar-S-TTFs possessing the first redox potential (E1/21) smaller than 0.6 V could form the co-crystal-type complexes with fullerene molecules C60 and/or C70, whereas those with E1/21 > 0.6 V could

• –S15). Complex 5·C70 crystallizes in the triclinic space group P-1 with one molecule 5 and one C70 crystallographically unique (Figure 1a). The central TTF core on molecule 5 has a chair conformation. The molecular geometry of 5 in the co-crystal, both the spatial alignment of pyridyl groups and the

• the AB sheet. The AB and CD sheets alternate along the crystallographic c-axis. Co-crystal 2·(C70)4·(PhCl)2 This complex crystallizes in the monoclinic space group C2/n, and the asymmetric unit contains half of molecule 2, two C70 molecules (A and B), and two halves of PhCl molecules. The central C6S4

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• protocol for resolving the racemate on large scale using (S)-BINOL was reported [88]. This method works via the co-crystal formation between (S)-BINOL and cis-(−)-lamivudine forming a binary complex which was characterised by single crystal X-ray crystallography. Raltegravir (3.18, Isentress), is another

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• ) predicted to interact with the tryptophan ring of (R)-5 (Figure 2A). This same hydrophobic site in TcCYP51 binds the fluoroaryl rings of fluconazole and posaconazole in co-crystal structures [14]. The predicted binding mode of the enantiomer (S)-5 was described previously [16] and is distinct from that

Intraannular photoreactions in pseudo-geminally substituted [2.2]paracyclophanes

• Henning Hopf,
• Vitaly Raev and
• Peter G. Jones

Beilstein J. Org. Chem. 2011, 7, 658–667, doi:10.3762/bjoc.7.78

• common disadvantage of solid-state photoreactions is the difficulty in predicting and controlling reaction selectivity. It remains a challenge to find the suitable crystal, co-crystal, or inclusion complex for the desired regio- or stereoselective outcome of a given reaction. Therefore, an attractive

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57