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

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• alcohol functionality takes place. It is mentionable that under the reaction conditions no aromatic iodination could be observed. Next to sodium iodide other iodide sources such as KI, I2 or Bu4NI can be used, whereas applying other halogenides such as NaBr, Et4NBr or Bu4NCl led to a complex mixture of

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• ). A similar behaviour is observed in the presence of the double-stranded lipid DOPC, which typically forms vesicles with membrane double layers. To determine the orientation of 32a in the membranes quenching experiments with KI were undertaken (for details see Supporting Information File 1). We found

• a rapid decrease of the pyrene fluorescence to ca. 50% at low KI concentrations whereas considerably higher KI concentrations were required to quench the fluorescence below 50%. This outcome clearly indicates that the AR is incorporated with a perpendicular orientation to the membrane surface

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• , the use of 0.2 equiv of KI as an additive afforded 2a in a satisfactory 95% yield (Table 1, entry 6). The base loading had a strong influence on the yield with 2 equiv KOH being the optimal amount (Table 1, entries 7 and 12). Further screening of bases did not lead to better yields and confirmed that

• -fluorophenylacetylene derivatives. Copper-promoted reaction of 2-fluorophenylacetylene derivatives to yield benzo[b]furans. Reaction conditions: Alkyne 1a (1.0 mmol), catalyst (10 mol %), KOH (2.0 mmol), H2O (1.5 mmol) and KI (0.2 mmol) in 3 mL of DMSO at 80 °C for 4–8 h; yields are given for isolated products. Copper

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• spectra with those from the NIST/EPA/NIH Mass Spectral Library 2.0 (2002). The second method involves comparison of the calculated Kovats index (KI) for some compounds with those previously determined by our research group. The KIs were obtained by interpolating the retention time (tR) of the compound in

• the KI versus tR graph obtained for the C8–C20 alkane standard mixture analyzed under the same conditions by GC–MS. Statistical analysis The β-CD encapsulation-competition data and the main descriptor indicating the hydrophobicity of the compounds (log P – the logarithm of 1-octanol/water partition

• (OM and OS); the encapsulation efficiency and hydrophobicity were the PCA variables). The GC–MS data (Kovats index – KI, relative concentrations – Area (%)) of the raw (B) and recovered from β-CD complex (B/β-CD) of O. basilicum L. essential oil, the relative encapsulation efficiency (E.E.) and the

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• : positive result; b) left: control, control with premature addition of 60% ethanol solution (before solution has fully cooled down and colour has vanished). Synthesis of nanodiamond derivatives carrying primary amino groups. a) Δ, b) 18-crown-6, KI, c) BH3·THF, d) 4-aminobenzonitrile, isopentyl nitrite, e

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• very strong inhibitor, with a Ki value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes. Keywords: furan synthesis; gold-catalysed cyclisation

• , which binds 25,000 times more strongly (Ki = 14 pM) than ThDP to PDC from Zymomonas mobilis (ZmPDC) and 500 times more strongly (Ki = 5 nM) to the E1 component of α-ketoglutarate dehydrogenase [10]. This extremely tight binding can be rationalised by the structural similarity between 2 and the ylid of

• . Two triazole analogues 3 (Ki = 20 pM) and 4 (Ki = 30 pM against ZmPDC) were synthesised in just four synthetic steps [12]. However, there is no possibility of attaching a substituent at the 2-position of the triazole to mimic enzymic reaction intermediates. Another analogue of ThDP 5 with a benzene

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• multivalent binding model gives effective molarities (EM) of 0.33 mM for the system 1/8 and 0.22 mM for the system 3/8 (Table 2). In combination with the intrinsic binding constants Ki of both systems the specific chelate cooperativities can be calculated by multiplication of EM and Ki. With these values a

• inclusion complex is formed first. In the second step the intramolecular complexation between the n-butyl moiety of 9 and the α-CD of 2, (Ki ≈ 102 M−1) has to appear to build a double stranded structure. Here again a negative chelate cooperativity is present (Ki·EM ≈ 0.03), preventing the intramolecular

• from the heterodivalent system 2/9 it is obvious that during the interaction between 5 and 12 first the complexation between the adamantane of 12 and the β-CD of 5 takes place. The following intramolecular complexation of one of the n-butyl moieties by one of the α-CD (Ki ≈ 102 M−1) does not occur due

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• ) – inhibitors of thymidine phosphorylase isolated from spontaneous lymphoma of SD rats (IC50 = 15 and 11 nM, respectively) [4], guanine derivative 5 – a potent inhibitor of human purine nucleoside phosphorylase PNP (Ki = 10 nM) [5], and finally guanine derivative 6 – exhibiting inhibitory activity against 6

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• presence sodium acetate in dioxane at 100 °C. The compound was prepared on the 10 mg scale in 67% yield. In contrast to its (3R,4R)-enantiomer (not shown), compound (3S,4S)-23 showed inhibitory activity toward human purine nucleoside phosphorylase (PNP) with a slow-onset binding constant Ki* = 0.032 nM. In

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• inhibitory activity (Ki, μM) against jack bean α-mannosidase. Supporting Information Supporting Information File 48: Mannosidase inhibition assay procedures, synthesis and NMR spectra of all new compounds. Acknowledgements This work was supported by the Institut Universitaire de France (IUF), the CNRS (UMR

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• change of KI-starch test paper), which destroy product 1 during concentration and drying under vacuum. And neither addition of urea (reacting with HNO2 to release N2, CO2 and H2O) nor passing of crude product 1 through a short silica gel column can stop its decomposition. So three reductants were

Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

• Friedrich Malberg,
• Jan Gerit Brandenburg,
• Werner Reckien,
• Oldamur Hollóczki,
• Stefan Grimme and
• Barbara Kirchner

Beilstein J. Org. Chem. 2014, 10, 1299–1307, doi:10.3762/bjoc.10.131

• differences such as substitution or dealkylation. Acknowledgements We would like to thank the DFG in the framework of the collaborative research center SFB 624 “Templates” at the University of Bonn for the funding of this research. Furthermore, the financial support of the DFG project KI 768/7-1 is gratefully

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• are located inside the cavity. (a) i) HCl, NaNO2/H2O, then KI/H2O, 58%, ii) Ph2PH, Pd(OAc)2, Et3N, MeOH, 48%; (b) i) CH3COOH, H2SO4, CCl4, I2, IO3, 85 °C, 4 h, exclusion of light, 70%; ii) C5H5N, H2O, KMnO4, reflux, 24 h, exclusion of light, 55%; iii) KOH in water (10% w/v), KMnO4, reflux, 4 h

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• transcarbamoylase (ATCase). 5-Membered 26 was completely inactive, whereas 6-membered 29 showed modest activity (Ki = 1 μM, 63 times less active than phosphonic acid N-phosphonacetyl-L-aspartate PALA, Ki = 16 nM). 1,3-Azaphosphorines and 1,3-azaphospholidines Several 1,3-azaphosphorines and 1,3-azaphospholidines

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• metabolites and copies of 1H and 13C NMR spectra. Supporting Information File 182: Additional experimental details and NMR spectra. Acknowledgements This work was supported by the Deutsche Forschungsgemeinschaft (grant Ki-397, 13-1) and the Fonds der Chemischen Industrie.

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• examples include using bis(trifluoromethyl)mercury (Hg(CF3)2) under the promotion of NaI (Scheme 1, reaction 3) [24] and using methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (MDFA) under the promotion of KI (Scheme 1, reaction 4) [25]. Our group has focused on the development and application of new

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• NaOCl solution in an amount that sufficed for showing a positive potassium iodide/starch test for 30 min, at which time this residual NaOCl was forthwith destroyed by solid NaHSO3 that had to be added until the KI/starch test became negative. (KMnO4 in place of NaOCl was found to decompose 17.) The

Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl)-3H-1λ³,2-benziodaoxol-3-one

• Nico Santschi,
• Roman C. Sarott,
• Elisabeth Otth,
• Reinhard Kissner and
• Antonio Togni

Beilstein J. Org. Chem. 2014, 10, 1–6, doi:10.3762/bjoc.10.1

• and the grey precipitate was filtered off and washed with copious amounts of water. Then, the filtrate was suspended in water (100 mL), heated to 100 °C and treated with a solution of KI (8.5 g, 51.2 mmol, 1.3 equiv) and H2SO4 (5 drops) in water (10 mL) over the course of 1 h. Finally, the brown