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

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• nitrogen protection (Scheme 3). A first attempt here involved the reaction of 5 with PMBCl in DMF, using K2CO3 alongside KI. Two separable regioisomers 11 and 12 were isolated in an acceptable 53% overall yield and in a ratio of N1-PMB/N2-PMB = 1.1:1 (Scheme 3). HMBC NMR of 11 and 12 clarified the position

• , DMAP, DMF, rt, 24 h, 87%; h) TMSN3, Bu2SnO, toluene, 120 °C, 51%. a) PMBCl, KI, K2CO3, DMF, rt, 53% for 11 and 12; b) BnBr, DMF, Et3N, DCM, rt, 31% for 13 and 14. a) DMSO, SO3·pyridine, Et3N, rt, 1 h, 96%; b) H2NOH·HCl, THF, H2O, Na2CO3, 89%; c) POCl3, MeCN, 65 °C, 59%; d) TMSN3, Bu2SnO, toluene, 120

• °C, 55%; e) PMBCl, KI, K2CO3, DMF, 76% for 18 and 19; f) 3-(benzyloxycarbonylamino)-propan-1-ol, NIS, AgOTf, CH2Cl2, −40 to −10 °C, 3 h, 34%; g) H2(g), Pd/C, Pd(OH)2/C, HCl, EtOH, THF, rt, 56 h, 96%; h) dibenzyl phosphate, NIS, AgOTf, CH2Cl2, −30 to 0 °C, 3.5 h, 72%; i) H2(g), Pd/C, Pd(OH)2/C, 5

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• previously reported to bind to the cannabinoid receptors, CB1 (Ki 4.3 µM) and CB2 (Ki 1.1 µM) [41]. Both receptors are considered important therapeutic targets, e.g. for neurodegenerative and inflammatory diseases. Selected final products (3a, 3b, 3e, 3g, 3h, 3n, 3ad) were tested for their binding affinities

• bearing 5-OMe,6'-F (3e), 5-OMe,7'-Br (3g), and 5-OMe,5',6'-diF substitution (3h) exhibited similar binding affinities to lead compound I. 5,6-DiF-DIM derivative 3n (CB1: Ki 2.04 µM) showed a slightly improved binding affinity compared to lead compound I. These results suggest that compounds with small

• substituents like fluoro on only one indole ring are favorable for CB receptor binding. The pentafluoroethylated DIM derivative 3ad was the best CB1 ligand of the present series with a Ki value of 1.82 µM. The binding curves of 3e and 3ad are depicted in Supporting Information File 1, Figure S1. Compound 3e

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• . Biphenyl-derived mycotoxins. Synthesis of arylboronates 6. Conditions: a) TBSCl, DMAP, imidazole, DMF, 50 °C, 4 h (96%); b) NBS, MeCN, rt, 71 h (quant.); c) NBS, MeCN, rt, 72 h (R = TBS, 96%); d) BnBr, KI, K2CO3, DMF/acetone, 70 °C, 29 h, (R = Bn, 86%); e) R = TBS: BuLi, 2-isopropoxy-4,4,5,5-tetramethyl

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• pyrrole-3-carboxamides. In the presence of 1.2 equiv of KI, a polysubstituted pyrazolo[3,4-b]pyridine derivative was also successfully synthesized. Keywords: acid catalyst; [1 + 2 + 2] annulation; KI; pyrazolo[3,4-b]pyridine; pyrroles; Introduction Among nitrogen-containing heterocycles, pyrroles have

• synthesis, we also observed an unexpected reaction in which the pyrazolo[3,4-b]pyridine scaffold was constructed under analogous conditions. As shown in Scheme 6, In the presence of a catalytic amount of AlCl3 and 1.2 equiv of KI, 3-methyl-1-phenyl-1H-pyrazol-5-amine (1b) reacted smoothly with 2a and 3a

• aromatization to produce 5a. KI may play a key role in the last step, and we suspected that it can promote the removal of bromide. Although 5a can theoretically be synthesized through a three-component reaction of 1b, 2a, and an appropriate aldehyde, for example, acetaldehyde [50][51] owing to the insufficient

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• . Conditions: i) potassium phthalimide, DMF, 25 °C, 18 h, 67%; ii) 2,2'-dipicolylamine, K2CO3, KI, acetone, reflux 14 h, 50%; iii) N2H4⋅H2O, ethanol, 25 °C, 16 h, 56%; iv) (R)-lipoic acid, EDC⋅HCl, DMAP, CH2Cl2, 25 °C, 18 h, 52%. Minimum salt concentrations required to precipitate and to subsequently

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• yield. Next, compound 202 was treated with KI/NaNO2 under Sandmeyer reaction conditions to afford the triiodo compound 203 which on subsequent reaction with mCPBA and triflic acid (TfOH) provided the iodine-doped sumanene 204 in 68% yield. Finally, compound 204 was converted to the required

• sumanene building block 204. Furthermore, the precursor 204 was converted to the 1,4,5,8,9,12-hexaiodotriphenylene 208 via ring-opening with KI in the presence of a copper/diamine catalyst (Scheme 50). Gratefully, compound 208 was also used as building block for the construction of heterasumaneness 151

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• are listed in Table 1. Firstly, the UDP-Galf native donor substrate was docked into the GlfT2 crystal structure to observe the reference docking score and to predict the Ki value for the native donor substrate. The predicted Ki value of the UDP-Galf is 0.333 µM, however, the experimentally observed Km

• Km or Ki values of the structures similar to the studied compounds were not available and therefore we were not able to create a more precise linear regression model for the binding affinity prediction. For this reason, we could use only a coarse correction for the calculated Ki values and the

• experimental Ki values can be expected in the mM and sub-mM range rather than in the µM and sub-µM range. However, the obtained predicted Ki values were reliable for the comparison of the fructofuranose and tagatofuranose compounds binding affinities with the UDP-Galf binding affinity. Moreover, the Ki values

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• activator but encouraging results were not obtained (Table 1, entries 11–15). Similarly, the use of KI as an activator also failed to promote the reaction (Table 1, entry 16) [62]. Eventually, we came to the conclusion that a combination of Et3N and DMSO excellently activated elemental sulfur at 70 °C and

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• ) MeOTf, CH2Cl2, 25 °C, 2.5 h; 2) NaBH4, THF/MeOH 4:1 v/v, 0 °C, 2.5 h; 3) oxalic acid, THF/H2O 4:1 v/v, 25 °C, 20 h, 85%. Overall yield from 4-methylbenzaldehyde to 4: 41% (5 steps). Reaction conditions: a) Br2, Fe powder, CHCl3, 0 °C, 4 h, 99%; b) KOH, KI, MeI, DMSO, 25 °C, 18 h, 92%; c) 1) n-BuLi, THF

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• ppm) or tetramethylsilane (δ = 0 ppm). Mass spectrometry was performed using a MALDI–TOF spectrometer AB SCIEX TOF/TOF 5800 system using 3-hydroxycoumarin or α-cyano-4-hydroxycinnamic acid as a matrix in combination with KI for the ionization. Unless otherwise stated, all starting materials, catalysts

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• . NaN3 and KI were added to the reaction mixture, and this was heated at 60 °C for two days to afford the azido-functionalized GO GO@N3 (82). In the next time, tripropargylamine (83), CuSO4, and sodium ascorbate were added to dispersed 82. The azide/alkyne “click” reaction proceeded well at rt over two

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• conditions. Toluene was very effective in our previous reaction system [17] but was not effective at all in this case (Table 1, entry 2). The reaction without NaI resulted in the formation of 3a-Br in 30% yield, instead of 3a (Table 1, entry 3). If KI was used instead of NaI, the yield of 3a decreased (Table

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (Ki = 0.011 µM) and I23 (Ki = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (Ki

• title compounds displayed promising AtHPPD inhibitory activities, with Table 1 and Table 2 revealing that compounds I12 (Ki = 0.011 µM) and I23 (Ki = 0.012 µM) exhibit similar inhibitor potencies to that of mesotrione (Ki = 0.013 µM). Docking studies using the CDOCKER module within Discovery Studio 4.0

• -withdrawing and electron-donating groups were introduced onto the benzene ring of I1, which significantly influenced the HPPD inhibition activity. We found that electron-withdrawing groups improve the activity; for example, I3 (Ki = 0.36 µM) and I4 (Ki = 0.59 µM) were more potent than I1 (Ki = 1.5 µM) and I2

Preparation of anthracene-based tetraperimidine hexafluorophosphate and selective recognition of chromium(III) ions

• Qing-Xiang Liu,
• Feng Yang,
• Zhi-Xiang Zhao,
• Shao-Cong Yu and
• Yue Ding

Beilstein J. Org. Chem. 2019, 15, 2847–2855, doi:10.3762/bjoc.15.278

• of 58% [41]. Compound 1 was then treated with SOCl2 to generate 9,10-bis{[N,N-di(2-chloroethyl)amino]methyl}anthracene (2) in 75% yield, which reacted with 1-ethylperimidine in the presence of KI to afford the analogous iodide salt to tetraperimidine 3. Subsequently, an anion exchange reaction with

• diethanolamine (9.988 g, 95 mmol) and K2CO3 (25.015 g, 181 mmol) in 100 mL of CH3CN/CHCl3, 1:1, v/v was stirred under reflux for 1 h. Subsequently, 9,10-bis(chloromethyl)anthracene (8.255 g, 30 mmol) and KI (0.914 g, 5.5 mmol) were added to the solution, and the mixture was reacted for 30 h at 35 °C. Then, the

• (1.177 g, 6 mmol), 9,10-bis{[N,N-di(2-chloroethyl)amino]methyl}anthracene (2, 0.389 g, 0.8 mmol), and KI (0.5 g, 3 mmol) in 30 mL of DMF/dioxane, 1:4, v/v was stirred under reflux for 5 days. After the solvent was removed, water (50 mL) was added to the residue. This was extracted with CHCl3 (3 × 30 mL

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

• (trans-isomers) bind CXCR3 with Ki values in the high nanomolar range. In contrast, compounds 2a–e after 360 nm illumination bind CXCR3 with Ki values in the low micromolar range, although the observed photoinduced affinity shifts (PAS) are not large (<4.0-fold). To assess if the compounds have agonist

• electron delocalization of π-electrons that is translated to a bathochromic shifting of the band to lower energy wavelength (337 nm). PSS values of 81–92% are obtained when illuminating with 360 nm light. The binding properties of 3a–h also result in outcomes similar to those of 2a–e. That is, Ki values

• ) pTsOH·H2O (3.0 equiv), MeCN, 10–15 °C; ii) NaNO2 (2.0 equiv), KI (2.5 equiv), H2O, 10–15 °C to rt, 2 h, 13%; (c) i) Et3N (1.2 equiv), DCM, rt, 30 min; ii) NaBH(OAc)3 (1.6 equiv), rt, 16 h, 54%; (f) MeI (20 equiv), DCM, rt, 20 h, 57%. Synthetic strategies for compounds 6f–h (Y = OMe, OiPr, SMe). Reagents and

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• evokes the synthesis of IL-6, INF-γ and TNF-α (see section “Abbreviations” at the end of the text). Furthermore, compound 2 has a very similar structure to the well-described SL thapsigargin, which is the best-known inhibitor of sarcoplasmic/endoplasmic reticular calcium ATPase (SERCA) with Ki values in

Halide metathesis in overdrive: mechanochemical synthesis of a heterometallic group 1 allyl complex

• Ross F. Koby,
• Nicholas R. Rightmire,
• Nathan D. Schley,
• Timothy P. Hanusa and
• William W. Brennessel

Beilstein J. Org. Chem. 2019, 15, 1856–1863, doi:10.3762/bjoc.15.181

• energies of formation of CsI and KI (−341 and −325 kJ mol−1, respectively; ∆∆G = +16 kJ mol−1) [26] means that the formation of the metal halide byproduct (KI) is non-spontaneous, and does not contribute to the driving force for the reaction. The relative free energies of the allyl complexes then must

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• (Scheme 3). In order to exclude false positive hits, two biorthogonal assays were chosen; 1H,15N HSQC NMR and fluorescence polarization (FP, Table 1). FP assay was employed to determine the inhibitory affinities (Ki) of the derivatives against MDM2 as previously described [36]. Besides 2h (Ki = 2.3 μΜ, Kd

• = 12.1 μΜ), it was shown that 2i demonstrated a promising activity with a Ki of 5.5 μΜ. Furthermore, 1H,15N HSQC showed a Kd of 4.8 μΜ (Table 1, Figure 2). Moreover, macrocycles 2g and 2n demonstrated a Kd of 9 μΜ and 17 μΜ, respectively (Table 1). With this preliminary analysis, it was found that a ring

• the size number of the macrocycle. Measurement of Ki and Kd of the selected macrocycles based on FP and 1H,15N HSQC NMR assays, respectively.a Supporting Information Supporting Information File 54: Experimental procedures, analytical data, NMR spectra, fluorescence polarization binding assays, 1H,15N

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• eigenvalue in the Hessian second order matrix) [28][38][39][40][41]. Structures of some bioactive 4-oxoquinoline-3-carboxamide derivatives 1–4 with different bioactive profiles. Ki = binding affinity; AHA = acetohydroxamic acid (standard urease inhibitor); SAHA = suberoylanilide hydroxamic acid (an FDA

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• ) Na2CO3, ACN, 80 °C, 24 h, 33%. a) MsCl, Et3N, DMAP, DCM, −78 °C to rt.; b) Na2CO3, KI, ACN, reflux. a) AllBr, TBAB, PhMe, 50% NaOH, 50 °C, 18 h, 94%; b) i. O3, DCM, −78 °C; ii. NaBH4, DCM, MeOH, rt, 16 h; c) MsCl, Et3N, DMAP, DCM, −78 °C to rt, 43% over 3 steps; d) Na2CO3, KI, ACN, 15, reflux. a) 50

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• . Accordingly, the titration was carried out and, indeed, even at (R)-mandelate concentrations well in excess of its Ki value of 1 mM [49], no change in the spectrum was observed (see Supporting Information File 1 for details). Discussion Since it was first purified from beer yeast over 80 years ago [51], the

• to be a competitive inhibitor of both transketolase and PDC, with a Ki value for the latter only ca. 20 times the Km for ThDP measured in the same experiment [56]. The current calculations show that, in the presence of substrate, TC/TCH+ are the most stable states of ThDP on BFDC. Yet, even though a

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• concentrations may be sufficient to define kcat and kcat/Km and Ki for product inhibition. The ready availability of computer programs for fitting by numerical integration of the rate equations renders the initial velocity measurements obsolete. In setting up initial velocity measurements one must first decide

• this case, kcat and kcat/Km can be approximated as follows (Note Ki = ki/k−i): Note that kcat is not simply defined by k3; rather, the equilibrium constant for the conformational change step defines the fraction of the bound substrate that is in the FS state (K2/(1 + K2)). An unfavorable equilibrium

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

• competition assay. Of the twenty compounds evaluated, five showed Ki values in the high micromolar range, but only vedaprofen, bromfenac and carprofen (13–15, Figure 3) displayed the strongest effects (Ki < 300 μM) [64]. Similarly to the preliminary study by Yin et al. [62] the antibacterial activity of the

• potent with a Ki of 12 μM as measured by a FP competition assay [87]. Kenny et al. succeeded in obtaining a crystal structure of 34 bound to ZipA which provided detailed knowledge of the basis of the binding mode. Interestingly, it was found that, although 34 occupies only half of the ZipA/FtsZ binding

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• Discussion PSMA has a very high affinity [39] for a small molecule homing ligand called DUPA or 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid with an inhibition constant Ki of 8 nM. Folate protein binds to folic acid and their derivatives [40] such as pteroate ligand [41] with high degree of specificity