Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• =CH]-Gly and Phe-ψ[(E)-CF=CH]-Gly for the peptide transporter PEPT1 was investigated (see Scheme 17) [51]. As the (Z)-monofluoroalkenes had a better bioactivity than the (E), the conclusion was that the transporter preferred the s-trans peptide bond. The Ki values obtained were also compared to the

• mobilizing response in GPR103-transfected cells of different 26FRa analogues. Ki values of Phe-Gly and analogues based on inhibition of [3H]Gly-Sar uptake by PEPT1 in Caco-2 cells. Anti-HIV activities of FC131 and its fluorinated derivatives against three HIV strains. Anti-HIV activities of SC29EK and its

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• that when NaI, LiBr or KI was used alone in anhydrous solvents (acetone, MeCN or butanone) under heating (80–100 °C) a selective monodeprotection of the dialkyl phosphonates (alkyl = methyl or ethyl) was observed. The sodium or lithium salts being formed in high yields (87–97% yields) [170]. This

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• as KI, I2 or KIO3 could all catalyze the domino reaction to provide product 3a, wherein KIO3 displayed the highest catalytic activity (entries 2–4, Table 1). On the other hand, in the reactions performed in different media, including DMSO, ethyl lactate (EL), EtOH, MeCN, 1,4-dioxane and toluene, DMF

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• tetracyclic Erythrina alkaloids which were isolated from Erythrina species in the end of the 19th century; the majority of this family possesses neuromuscular blocking effects [2]. DHβE is one of the most potent nAChR antagonists of this class and displays prominent selectivity for the α4β2 subtype (Ki = 0.82

• studies concerning the construction of new designed [6,6]-bicyclic lactones and the deconstruction of the DHβE scaffold are currently underway in our laboratory. DHβE and related structures. The Ki values of the compounds at the rat α4β2 nAChR subtype determined in a [3H]cytisine binding assay are given

Substitution of fluorine in M[C₆F₅BF₃] with organolithium compounds: distinctions between O- and N-nucleophiles

• Anton Yu. Shabalin,
• Nicolay Yu. Adonin and
• Vadim V. Bardin

Beilstein J. Org. Chem. 2017, 13, 703–713, doi:10.3762/bjoc.13.69

• and PhLi were prepared from lithium and MeI or PhBr, they contain the corresponding lithium halides. It follows that the precipitate consists of KI and KBr, respectively, and the actual boron-containing reactant is lithium pentafluorophenyltrifluoroborate (1-Li). Independently, Li[C6F5BF3] was

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• intermediates, we first needed to synthesize the syn-dihydroxy esters 19 and 20 (Scheme 4). Toward that objective, 2-allyl-4-fluorophenol (15) was benzylated with BnCl and anhydrous K2CO3 in the presence of KI in acetone under reflux conditions to obtain benzyl ether 16 (Scheme 4). The subsequent hydroboration

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• described in literature [28]. First, PMMA was spin coated as a supporting layer. Then, the mica was removed by floating in solutions of I2/KI/H2O; KI/H2O and in the last step by immersing the substrate in H2O. The retaining gold film was etched in a solution of I2/KI/H2O. The membrane was washed 3 times

• then obtained by following a procedure described in literature [29]: First PMMA/PS was spin coated as a supporting layer and afterwards rinsed overnight in cyclohexane to remove the PS. Then, the mica was removed by floating in solutions of I2/KI/H2O; KI/H2O and in the last step by immersing the

• substrate in H2O. The retaining gold film was etched in a solution of I2/KI/H2O. The membrane was washed 3 times with water [28]. Afterwards the membrane was transferred to either a glass slide or a gold coated Si-wafer. The obtained membrane size was 2 cm × 2 cm. LbL synthesis with TPM-SH and TPM-alkyne

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• a functionalized resin by simple washing with aqueous KI3/KOH solution makes the process more sustainable. This method produces KI solution as waste, and it is an alternative way for the direct oxidation of hydrazones, that often requires the use of heavy metals such as HgO, Pb(OAc)4 and AgO [82][83

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• of the of cross-polarization contact time, t, is expressed as follows (Equation 1): where kIS is the rate constant for the “heat flow” between the I and S spins, and kI, kS are the inverse of the spin-lattice relaxation times in the rotating frame for the spin I (T1ρ(H)) and S (T1ρ(S)), respectively

• . The simplified Equation (2) is obtained assuming that: 1) kS < kIS (kS is negligible), 2) kIS + kS > kI, the system is in the fast CP regime. According to Equation 2, the magnetization of the S spins rises with the CP rate constant kIS, reaches the maximum SCPMAX at time tMAX and, subsequently

• , decreases with the time constant kI. Some experimental curves showing the trends mentioned before are shown in Figure 7. Finally, the two relaxation parameters TCH and T1ρ(H) can be determined, in principle, by fitting the experimental curves with the bi-exponential Equation 2. The I–I*–S model In the I–I

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• , presumably due to steric hindrance. Cyclisation of 4 to the THQ 3 was realised by heating a PPA mixture of 4 to 120 °C. Iodination of 3 using a variety of reagents including I2/HgO [19], ICl/AcOH, N-iodosuccinimide/TFA [20], KI/KIO3/AcOH [21], and N-chlorosuccinimide/NaI/AcOH [22], all gave poor yields (0–30

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• of a research program on phosphonate derivatives of nucleosides as mimics of 5’-monophosphate nucleosides, we explored the SAR of various beta-hydroxyphosphonate analogues. Such derivatives have been extensively studied and exhibited Ki values in the same range as the known natural substrates (IMP

• , inosine 5’-monophosphate and GMP, guanosine 5’-monophosphate) [6][7]. In the particular context of cN-II, which is also known as High-Km nucleotidase owing to the high substrate concentration required for activity (in the mM range), the Ki values of approximately 1 mM previously obtained for cytidine

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• identified as a lead template with HIV protease inhibitory activity, i.e., Ki = 1 µM [64]. However, the prototype of these anticoagulant drugs was dicoumarol (60), which was in use until it was replaced by other derivatives, e.g., 58 and 59 [65]. Aflatoxins are poisonous and cancer-causing monobenzo-α

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• average number molecular weight (Mn) can be used to characterize the ratio of initiation rate to propagation rate (ki/kp) of a given initiator to monomer combination [28][44][45][46]. Under the applied conditions (prolonged reaction time, reaction temperature up to 100 °C, UV-irradiation) none of the

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• of 62 and Cu(ClO4)2 which enabled the halogenations by using simple alkali salts such as KF, LiCl, LiBr, KI, etc. as the source of halogen (Scheme 20). Besides in providing various halogenated arene products, the copper-catalyzed arene C–H halogenation had also displayed important application in

• a catalytic system consisting of (BPMED)CuI (copper(I) bisimine complex), N-hydroxyphthalimide (NHPI), KB(C6F5)4 and KI. The protocol allowed the selective fluorination of various substrates, including cycloalkanes and benzylic compounds using commercially available Selectfluor as fluorine source

• . According to the obtained results, the presence of KB(C6F5)4 as the phase-transfer catalyst could accelerate the reaction rate and enhance the yield of the products. On the other hand, the KI could promote the formation of the active cuprate species (BPMED)CuI2−, thus allowing less reactive substrates to

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• excess of KI) [14]. The side-product in the iodination of 3 was bis(pyridine)iodonium tetrafluoroborate, which can be easily isolated from the reaction mixture by precipitation upon addition of diethyl ether. This iodonium salt was first synthetized by Barluenga [85] and later used for mild iodination of

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• the synthesis of the N-arylated pyrroles and indoles 1a,b,d,e and 2a–e [44]. To azole (6.0 mmol) and aryl halide (4.0 mmol) in acetonitrile (20 mL) were successively added Cu (50 mg, 0.80 mmol), Cs2CO3 (2.6 g, 8.0 mmol) and, in the case of aryl bromides, KI (99 mg, 6.0 mmol). The mixture was stirred

Consequences of the electronic tuning of latent ruthenium-based olefin metathesis catalysts on their reactivity

• Karolina Żukowska,
• Eva Pump,
• Aleksandra E. Pazio,
• Krzysztof Woźniak,
• Luigi Cavallo and
• Christian Slugovc

Beilstein J. Org. Chem. 2015, 11, 1458–1468, doi:10.3762/bjoc.11.158

• propagation rate (kp) and the initiation rate constant (ki), provided that no secondary metathesis occurs. In this case, Mn is only dependent on ki, because in all cases the same propagating species occurs and kp is the same. Accordingly, initiator 14 exhibits the highest initiation efficacy and initiator 5a

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• failed, probably due to the steric hindrance exerted by a bulky substituent at the α-position. Electrochemical α-alkoxylation of N-acyl-α-amino acid esters mediated by NaCl, NaBr, LiCl, KCl or KI is a well-known reaction [38][42][43][44][45][46], whereas the analogous reaction of N-acyl-α-aminophosphonic

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• and conditions: (a) Ac2O, pyridine, 94%; (b) BnBr, KI, K2CO3, acetone, 85%; (c) Me2SO4, K2CO3, acetone, MeOH, 82%; (d) MOMCl, N,N-diisopropylethylamine (DIPEA), CH2Cl2, 93%; (e) 3,3-dimethylallyl bromide, 18-crown-6, K2CO3, acetone, 86%; (f) Eu(fod)3, NaHCO3, PhCl, 85 °C, 61%; (g) MeOH, 3 M HCl (aq

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• , which are substituted by different functional groups in the 4´-position and were characterized by X-ray crystallography. We aimed to investigate the influence of electron-donating or electron-withdrawing substituents on the inhibitory constant Ki. With the aid of an hCAII crystal structure bound to one

• of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with Ki = 25–65 nM that are potentially photochromic and thus combine studies from chemical synthesis, crystallography and enzyme

• distance for classical hydrogen bonding is rather long (3.2 Å). In order to determine the half-maximal inhibitory concentrations (IC50) and the inhibitory constants (Ki) towards hCAII for our library, we used a colorimetric endpoint measurement of the catalyzed pNPA hydrolysis (Figure 1a). Usually, a

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• displayed low micromolar to even sub-micromolar Ki values against GP (Figure 1) [9][10][11][12][13]. Benzo-fused aglycons [14][15] (A–C) were initially identified as beneficial for the inhibition of GP. 1,2,3-Triazolyl-based aglycon D [16][17] proved valuable for the inhibition of GP and further design

• the desired product. A series of seven glucose-based inhibitors of GP were then evaluated but did not display any inhibition against RMGPb at 625 µM. Structures of the glycosylated heterocyclic GP inhibitors and corresponding Ki values against RMGPb. Structures of the two targeted 3-glucosyl-5-amino

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• −. The HOO− will be subsequently protonated to yield H2O2 as the by-product. H2O2 was detected after the reaction was completed by using KI/starch indicator (see the Supporting Information File 1). The involvement of radical pathway was supported by experimental result that the reaction was suppressed in

Bis(vinylenedithio)tetrathiafulvalene analogues of BEDT-TTF

• Erdal Ertas,
• İlknur Demirtas and
• Turan Ozturk

Beilstein J. Org. Chem. 2015, 11, 403–415, doi:10.3762/bjoc.11.46

• ; (ii) LiAlH4, dry ether, rt, 24 h; (iii) tosyl chloride, dry pyridine, 0 °C, 4 h; (iv) KI, dry acetone, N2, reflux, overnight; (v) dry THF, 75 °C, N2, 48 h; (vi) P4S10, toluene, reflux, 3 h; (vii) Hg(OAc)2, AcOH/CHCl3, rt, 2 h; (viii) neat (EtO)3P, N2, 3 h; (ix) sample in THF at 0 oC , add 20% HCl

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• equiv), K2CO3, acetone, rt, ii: NH3 (g), MeOH, 84%. Reagents and conditions: (a) BnBr (1.9 equiv), KI, K2CO3, acetone, 85%; (b) i: AlCl3, CH2Cl2, CH3CN, reflux, ii: 1 M HCl (aq), 86%; (c) Me2SO4 (1.3 equiv), K2CO3, acetone, rt, 85%; (d) NH3 (g), MeOH, 96%; (e) Pd/C, H2, 91%; (f) MeOH, acetone, 1 M HCl