Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• prepared by a double displacement reaction between 2,6-dichlorothiobenzamide and 1,4-butylene dibromide [29]. In 1970, Mente prepared a dehydro analogue, namely 2-(4-chlorophenyl)-4,7-dihydro-1,3-thiazepine, via thermolysis of N-(4-chlorothiobenzoyl)-2-vinylaziridine [30]. No yields were reported for these

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• using an aqueous ammonium sulfide solution to furnish aniline 6 in 65% yield [20]. After oxidation of 6 to its nitroso analogue 7 [21], a Baeyer–Mills reaction with aniline yielded the targeted azobenzene building block 8 in 87% yield (i.e., 53% yield over four steps). After the successful synthesis of

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

• has been observed in many cases that exogenous substrates can be incorporated by bacteria into biosynthesis cascades of natural products. The use of substrates which lead to nonnatural derivatives of the natural product coined the field of mutasynthesis, e.g., siderophore analogue biosynthesis by P

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• compare the monofunctionalized BQ 2 with a difunctionalized analogue, 5 was also prepared for our investigation. As 2,5-difunctionalized BQs with electron-donating groups are not accessible via the Pd(II)-catalyzed direct C–H functionalization method utilized in Scheme 2 (since the selectivity for

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• (Scheme 2) showed supramolecular features, i.e., their DMSO solutions prepared for NMR analyses spontaneously transformed into gels inside the NMR tubes. Three cis-/trans-configured pairs of compounds were chosen for a gelation ability study. Thus, analogue pairs 8f/7f (Scheme 2), 10/9 (Scheme 3), and 14

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• penetration is an essential requirement of the compound but would be an ideal peripherally restricted control. These data will contribute to the understanding of drug levels of 1 to overlay with appropriate in vivo efficacy endpoints, i.e., the PK-PD relationship. The identification of a suitable analogue of

• tool by capping off the acid as an amide. Although significant Notum inhibition activity could be achieved, none of these amides demonstrated the required combination of metabolic stability along with cell permeability without evidence of P-gp mediated efflux. The identification of a suitable analogue

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• the Z-isomer-enriched PSS. Theoretical π–π* band separations for the E-isomers of 4pzMe-F2 and 4pzMe-Cl2 (Table 2) match very closely with the experimental data (Table 3), with the exception of the methoxy 4pzMe-OMe2 analogue. A large conformational space is expected for the twisted 4pzMe-OMe2 (vide

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• significant differences being the absence of the 6-OH proton, the presence of additional signals for a C6 acyl chain, and significant deshielding of H-6 from δH 4.30 to 5.47 ppm. Therefore, the structure of 2 was assigned as the 6-O-hexanoyl analogue of 1, as shown in Figure 1. Compound 2 was previously

• File 1) with those for 2 revealed the only significant differences to be the absence of the H-1 and 1-OH protons and the presence of an additional methylene group (H2-1). Therefore, the structure of 4 was assigned to be the 1-deoxy analogue of 2, as shown in Figure 1. Compound 4 was previously reported

• , while HMBC correlations from H-7 to C-12 and from H3-12 to C-9 positioned the methyl on C-8. Therefore, the structure of 8 was assigned as the seco analogue of 2, as shown in Figure 1. The absolute configuration of 8 was assigned to be the same as 2 based on their similar NMR data and optical rotations

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• clinical trials against colon cancer, gall bladder cancer and acute myelogenous leukemia in humans [40] and its 2-aza analogue 3 is also active against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) [41]. To the best of our knowledge, this case of α-imino silver-carbene is not yet

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• blood cells (see Supporting Information File 1, assay 3) [43]. Analogue 9e showed better capacity to inhibit the hemolysis than 9g at the same concentration (Figure 3). At concentrations of 10 µM and 200 µM of 9e, the hemolysis production by S. aureus was inhibited by 63% and 84%, respectively. Also, a

Formation of alkyne-bridged ferrocenophanes using ring-closing alkyne metathesis on 1,1’-diacetylenic ferrocenes

• Celine Bittner,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2019, 15, 2534–2543, doi:10.3762/bjoc.15.246

• analogue of the formula [Fe{C5H4COO(CH2)3 C≡}2]2 in a ratio of approximately 4:1. Related NMR spectra can be found in Supporting Information File 1 (Figures S9 and S10). Separation of the monomer 2b could be achieved with column chromatography on silica gel with a yield of 53%. The ring-closed dimer

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• induce apoptosis, and to induce generation of ROS. Compounds 11b and 11f were arbitrarily chosen, while the shorter chain analogue 11g was selected to compare the effect of chain length, if any. Direct comparison with SAHA was made to quantify the effects shown by these three compounds in each of the

• clearly the truncated analogue 11g is less effective. Loss of cell viability by LDH assay LDH assays quantitatively measures lactate dehydrogenase (LDH) released into the media from damaged cells as a biomarker for cellular cytotoxicity [35][36]. Hence, to further characterize compound-induced HeLa cell

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• azobenzene analogue 2a, we explored the substitution pattern of the outer aromatic ring with chlorine atoms in the ortho, meta and para-position (compounds 2b–d, respectively) to also assess the possibility of agonism provided by a halogen bond. Compound 2e, which contains a bromine atom in the ortho

• unit Aiming to improve the position and directionality of the halogen atom, we next designed a subseries with the azo group at the meta-position of the central ring (scaffold 3) instead of at the para-position as in 2a–e. The analogue without halogen substitution (3a) as well as Cl/Br analogues

• oxidation of methyl 3-aminobenzoate (17a) using Oxone® to obtain a crude nitroso product 18a, which was used in a Mills reaction with an iodoaniline (19a–c) at 100 °C to obtain azobenzenes 20g,h in high yields and ortho-analogue 20f in a decreased yield presumably due to steric hindrance. The methyl ester

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• melting temperatures (TM) by the analysis of the first derivative [50]. TM values are summarized in Table 2. The incorporation of the visible-light responsive azobenzene (PNA 3) stabilized the duplex in comparison with the Aeg(Ac)-modified analogue 5. However, the TM of 3 is 14 °C lower than the one

• calculated for the unmodified PNA analogue (20). Unfortunately, no difference between isomers was observed. The potential of the functionality of our compounds could be enhanced by both changing the localization and the number of incorporated photoswitches. To try to maintain the cooperative base pairing, we

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• demonstrated that imidazole as a heteroaryl moiety decreases thermal stability [42]. In particular, a close analogue of 3 with a phenyl instead of a pyridyl group showed a half-live of the ring-closed isomer as low as 7.3 days. In accordance to this data, diarylethene 3 showed a half-life of 8.6 days. However

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• of 1a–d and of the reference compound 7 calculated using B3LYP. The results show a pronounced effect of linker length on the energy difference between Z- and E-isomers. Ring strain for E and Z-isomers of 1a–d expressed as the Gibbs free energy difference to an acyclic analogue, using an isodesmic

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• structure of CotB2wt with bound inert substrate analogue geranylgeranyl thiodiphosphate (GGSDP; CotB2wt·Mg2+B·GGSDP; PDB-ID 5GUE; [36]), resembling the next precatalytic state of CotB2. Surprisingly, there is only Mg2+B bound to the enzyme and not the full set of three Mg2+-ions needed for catalysis. The

• [11]. Structural information on selina-4(15),7(11)-diene synthase (SdS), revealed that upon substrate binding by an induced fit mechanism, R178 changes its side chain conformation thereby approaching and interacting with the diphosphate function of the substrate analogue and forming a salt bridge to

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• optical properties for medical and bioimaging. As a compound with intrinsic mitochondria targeting ability, the radiolabelled analogue can be applied in multimodal (PET/OI) imaging of mitochondria for diagnostic and therapeutic use in, e.g., cancer patients. Keywords: halogen-dance reaction

• -fluoroazetidine moiety in 10 (“JF635”) causes a hypsochromic shift without affecting the high quantum yield compared to the azetidine analogue 9 (“JF646”) (Table 1, entry 9 vs 10). Comparing the phenyl substituted rhodamine 2 with its 2’-methyl substituted analogue 3, restricted rotation around the xanthene

• coexistence of 19 and its lithiated analogue. Using high excess of 19 could force the reaction to completeness leading to the dihalogenated pyridinyl silicon rhodamine in 85% yield without any monohalogenated byproduct and no necessity of HPLC purification. Although 15 can be coupled or further functionalized

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

• had utilised for the construction of oxoaporphine alkaloids before [21] failed to give kuanoniamine A (3, Scheme 4). In order to explore alternative cyclization protocols, we performed model reactions with 2-bromophenyl analogue 12c. Neither the reaction with diverse Pd catalysts, nor Oliveira’s Pd

• material could not be recovered, another product 23, which is most likely the debrominated, not cyclized analogue of 20a, was observed in traces. The outcome of this experiment shows that the bromine–magnesium exchange reaction was most likely completed, but the intramolecular trapping of the ester group

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• catalysis (Scheme 61). The method tolerates a myriad of primary, secondary and tertiary carboxylic acids and provides the corresponding CF3 analogue in good to excellent yields. Details of the proposed dual copper–photoredox cycle are shown in Scheme 61. The Ir(III) photocatalyst Ir[dF(CF3)ppy]2(4,4

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• ]. Mechanistically, isomerisation of 12 to the methoxy-NDP analogue 28 allows for an ADS-catalysed 1,6-cyclisation to the 12-methoxy-bisabolyl cation (29) followed by a [1,3]-hydride shift, which relocates the positive charge on C1 in 30. With FDP and 12-hydroxy-FDP, a subsequent 1,10-ring closure has been proposed

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• original stilbenoid structure exerted unfavourable photochemical characteristics it was remodelled to its heteroarylic diazeno analogue. By this intramolecular azologization, the shape of the molecule was left unaltered, whereas the photoswitching ability was improved. As anticipated, the highly analogous

• strength accordingly. Synthesis and photochemistry of photoswitchable diazeno analogue Even though the photochemical properties of ortho methylated azastilbenes like 2f could be improved by preventing photocyclization, they were still unsuitable for the use as photoswitchable sirtuin inhibitors in the

• stilbene motive of selected stilbene 2c by a diazeno group, because photoisomerization of azo dyes was anticipated to proceed fast and reversible by application of UV irradiation and visible light, respectively in this analogue. 5-Diazenylnicotinamide 11 was synthetically accessible in two steps through

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• its bis(imidazolium) analogue. Given that, the highest affinity of this heterophane system was toward acetate (Ka = 5.0 × 103 M−1) in CD3CN. Although the iodide ion is biologically important because of its indispensable role in thyroid gland function, among all of the reported receptors in the

• macrocycle has been reported by Nakamura and his co-workers containing three 1,2,3-triazolium and carbazole moieties 12 (Figure 10). π–π stacking interactions and the self-association ability of the synthesized macrocycle are increased in comparison with its neutral analogue due to the decreased electron

• density of the triazolium derivative. Rigid macrocycles 12 display selective complexation with I− because of the complementary size of the cavity of the macrocyclic ring and the iodide ion. In addition, the acidity of the inner protons of 12 is higher than the corresponding neutral analogue which also

Synthesis and properties of sulfur-functionalized triarylmethylium, acridinium and triangulenium dyes

• Marco Santella,
• Eduardo Della Pia,
• Jakob Kryger Sørensen and
• Bo W. Laursen

Beilstein J. Org. Chem. 2019, 15, 2133–2141, doi:10.3762/bjoc.15.210

• ] lacking para-substituents and for the para-amino-substituted analogue [17] (step 2 in Figure 1). It was found that the reactivity in SNAr reactions of 1 with primary amines was high and the acridinium compounds 4a,b were obtained in few minutes after the addition of 2 equiv of the corresponding primary

• (Figure 5), with increasing intensity as the number of -SEt groups on the TOTA+ core increases. This behavior resembles the trend observed for the analogue series of amino-substituted TOTA’s (Table 2) [18][31]. In the two low-symmetry derivatives 8 and 9 transitions to the S2 excited states are observed

• less bright fluorophores. Thus, the dialkylamino-substituted analogue of 5a (A3-ADOTA+) has a reported quantum yield as high as 64% in acetonitrile [17], on par with A3-TOTA+ and A2-TOTA+ which display quantum yields from 50–100% depending on the solvent [31]. A similar reduction in fluorescence

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• suggested that 1 was the 9-hydroxy analogue of 5, which was further confirmed by detailed analysis of key 2D NMR correlations (Figure 2). Compound 1 was previously reported in 1970 as a semi-synthetic analogue of 9-hydroxyprehelminthosporol [18], but has not been previously isolated and characterised from a

• difference being the presence of a hydroxymethylene group (δC 65.8; δH 3.58 and 3.44) in place of the methyl group at C-11. Thus, the structure of 2 was assigned as the 11-hydroxy analogue of 5. The absolute configurations of the chiral centres in 2 were established to be the same as for 1 after

• quaternary carbon (δC 74.8) in 3. This suggested that 3 was the 6-hydroxy analogue of 5, which was further confirmed by detailed analysis of key 2D NMR correlations (Figure 2). The absolute configurations of the stereocentres in 3 were established to be identical to 1 and 2 based on the analysis of proton