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

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

• mimetics More recently, Ji et al. published two classes of sulfonyladenosine inhibitors, more precisely the sulfamate/sulfamide inhibitors 5–9 and the vinyl sulfonamide inhibitors 10 and 11 (Figure 5). While the latter showed very low affinity for the protein, the former displayed Ki values between 88 nM

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• induced by the four salts ranged from 170 and 180-mers in the presence of KI and CsI, to ≈724-mers for NaI. Evidently the difference in the free energies of solvation of Br− and I− (ΔGhyd = −321 and −283 kJ mol−1, respectively) is key to allowing more ion pairing between the trimethylammonium groups of 2

• and I− to induce substantial aggregation. The data for the I− salts illustrate a further complexity to the ability of salts to induce precipitation of ammonium ions such as 2. Thus, although the aggregation induced by KI and CsI are not significantly different, there is a trend for cation-induced

• trend in the aggregation of 2 (NaI > LiI > KI ≈ CsI) is therefore not in full agreement with the LMWA. The LMWA correlates with our data that K+ and Cs+ should pair strongly with I– and therefore induce weak aggregation. However, it also predicts that Li+ and I− should form the weakest ion pair and that

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• . Regioselective ring opening of the sulfonium ion then provides the β-hydroxy sulfide 95. The R2SCu(I)Ln generated in the reaction is oxidized to form the disulfide and regenerates the Cu(I)Ln catalyst. 3.3.4 Acetoxysulfenylation of alkenes using DIB/KI. Muangkaew et al. reported a convenient method for 1,2

• -acetoxysulfenylation of alkenes using diaryl disulfide promoted by diacetoxyiodobenzene (DIB) and KI as shown in Scheme 37 [71]. The method is compatible with styrenes possessing various substituents, namely: halides, methoxy, hydroxy, nitro, ester and alkyl halides. Similarly, the nature of the substituents on the

• amount of iodine was used instead of stoichiometric amount of KI [72]. The proposed mechanism is depicted in Scheme 38 [71]. The DIB reacts with the iodide yielding acetylhypoiodite (97, AcOI) as an intermediate which according to the authors readily reacts with the disulfide 99. The thus formed

Synthesis of diamido-bridged bis-pillar[5]arenes and tris-pillar[5]arenes for construction of unique [1]rotaxanes and bis-[1]rotaxanes

• Ying Han,
• Li-Ming Xu,
• Cui-Yun Nie,
• Shuo Jiang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2018, 14, 1660–1667, doi:10.3762/bjoc.14.142

• The synthetic route for the pillar[5]arene mono(oxyalkoxy)benzoic acids was illustrated in Scheme 1. Firstly, the alkylation of mono(bromoalkoxy)pillar[5]arene 1a–c (n = 4, 5, 6) [64] with methyl or ethyl p-hydroxybenzoate was carried out in the refluxed medium of KI/K2CO3/CH3CN for one day. The

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• regioselective iodination of glycals by using CTAB and hypervalent iodine reagents for the synthesis of 2-deoxy-2-iodoacetates. In the preliminary experiments, the reaction between per-O-acetylglucal (177) and PhI(OAc)2 in CTAB and KI gave trans-2-iodo α-acetate and its corresponding bromo acetate in a 94:5

• ratio. The latter was expected to be formed by halide counter ion exchange between CTAB and KI. Since the reaction occurred as expected, it was applied to the synthesis of amino acid conjugates. Acetyl groups of the (diacetoxyiodo)benzene were exchanged with N- and O-protected amino acids by slow

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• case the analogous bromoethoxylated adduct 4a’ could be isolated in 68% yield, albeit along with 25% of 2a (Table 1, entry 6). Turning our attention to iodination, we first used the combination of PIFA and KI that had given the best results with enamides [13]. Thus, iodo(trifluoro)acetoxylated adduct

• 5a was obtained in 70% yield (Table 1, entry 7). Interestingly, no traces of the diiodo compound were observed even if the hypervalent iodine(III) reagent was slowly added. Transposing the previously optimized bromo(trifluoro)acetoxylation conditions but using TBAI instead of KI did not improve the

• did isolate dibromo adduct 2a but only with 47% yield and we also observed the formation of various byproducts such as ene-bromination adduct 6a’ (Scheme 7b) [27]. Moreover, for the iodination of enamides using the PIFA/KI combination we had already shown that the observed reactivity is more akin to

Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• Sang Won Park Soong-Hyun Kim Jaeyoung Song Ga Young Park Darong Kim Tae-Gyu Nam Ki Bum Hong Department of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of Korea New Drug Development Center (NDDC), Daegu-Gyeongbuk Medical

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• and sodium nitrite were used to generate the diazonium ion and then KI was used to introduce iodide, providing the desired product 7 in 87% yield. With 7 in hand, the synthesis of target ortho-SF5 phenylaryl-λ3-iodonium salts 3p, 4b, 5a and 6a was carried out according to a previously reported method

• allowed to stir at 0 °C for 15 min after which it was added dropwise to a cold stirred solution of KI (1.33 g in 10 mL distilled water) at 0 °C. The reaction was allowed to warm to room temperature then stirred for 20 min. The reaction mixture was extracted with diethyl ether (3 × 20 mL). The combined

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• Jun Ki Kim Hwan Jung Lim Kyung Chae Jeong Seong Jun Park Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology (KRICT), 141 Gajeong-ro, Yuseong-gu, Daejeon 34114, Korea Department of Chemistry, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134

Microfluidic radiosynthesis of [¹⁸F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

• Thomas Lee Collier,
• Steven H. Liang,
• J. John Mann,
• Neil Vasdev and
• J. S. Dileep Kumar

Beilstein J. Org. Chem. 2017, 13, 2922–2927, doi:10.3762/bjoc.13.285

• receptor, [18F]FEMPT (pKi = 9. 79; Ki = 0.16 nM) by microfluidic radiochemistry. [18F]FEMPT was obtained in ≈7% isolated radiochemical yield and in >98% radiochemical and chemical purity. The molar activity of the final product was determined to be >148 GBq/µmol (>4 Ci/µmol). Keywords: agonist; fluorine

• Psychoactive Drug Screening Program (NIMH-PDSP). FEMPT shows 0.2 nM binding affinity (Ki) to 5-HT1AR. The next closest bindings for MPT are Sigma2 PC12, H1, 5-HT7, and 5-HT1B (Table 1) and are >50 times higher than 5-HT1AR. The Ki values for several other brain receptors and transporters were low (0.1 to 10 μM

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• presence of the respective secondary amine, K2CO3 and KI in DMF (Scheme 6 and Table 4). Subsequent work-up and isolation by column chromatography furnished the desired 2-dialkylaminoalkyl-3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones 8a–y in moderate yields of 49–61% (Table 4), among these the