Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• caused ≥50% inhibition of [3H]diprenorphine binding. The Ki of 4 was 110 nM (Table 1), a substantial reduction in affinity relative to 1. None of these compounds showed detectable affinity for µ- or δ-OR (Ki > 1 μM in all cases). Thus, 4 showed modest affinity and selectivity for κ-OR, while 2, 3 and 5

• showed no affinity for any opioid receptor. Follow-up testing in the [35S]GTPγS functional assay demonstrated that 4 was an agonist less potent than 1 at κ-OR, but giving an equal maximal response (Table 1). (2-Hydroxyethoxy)methyl ether 6 showed high affinity for κ-OR, but not for µ- or δ-OR (Ki > 1 μM

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• oxocarbenium ion, the iminosugars 31 and 41–44 (Figure 11) must bear a positive charge, and since the pKaH values vary considerably amongst the different derivatives, it follows that each derivative has a different “optimal” pH for maximal inhibitory potency. This explains why the Ki values in Figure 11 do not

• seem to follow a clear trend: the quoted Ki values were all measured at the same pH, whereas it would be more revealing to consider the Ki of each molecule at its “optimal” pH. This is a very interesting situation, because it opens up the possibility of developing drugs that are selective for

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• CaCl2, 1 mL mineral solution (consisting of 0.1 g H3BO3, 5 g FeSO4·7H2O, 0.05 g KI, 2 g CoCl2·6H2O, 0.2 g CuSO4·5H2O, 2 g MnCl2·4H2O, 4 g ZnSO4·7H2O, 1 g 95% H2SO4 for 1 L solution), 10 mL vitamin solution (consisting of 10 mg folic acid, 6 mg biotin, 0.2 g p-aminobenzoic acid, 1 g thiamin·HCl, 1.2 g

Structure of 1,5-benzodiazepinones in the solid state and in solution: Effect of the fluorination in the six-membered ring

• Marta Pérez-Torralba,
• Rosa M. Claramunt,
• M. Ángeles García,
• Concepción López,
• M. Carmen Torralba,
• M. Rosario Torres,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2013, 9, 2156–2167, doi:10.3762/bjoc.9.253

• . 6,7,8,9-Tetrafluoro-1,4-dimethyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one (2). A solution of 1 (0.40 g, 1.62 mmol) in DMF (2 mL) was heated at 110 °C in the presence of iodomethane (0.11 mL, 1.79 mmol), K2CO3 (0.27 g, 1.95 mmol) and a catalytic quantity of KI for 90 min. The mixture was cooled, treated with

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• aminals. Here we present catalytic methods for the synthesis of both these compound classes from aminals using Cu(OAc)2/O2/AcOH and KI/TBHP systems, respectively. Results and Discussion Copper-catalyzed oxidations of aminals to dihydroquinazolines Copper-catalyzed oxidation reactions have received a great

• did not reach completion after 3 days. The attenuated reactivity of aminal 19 is most likely the result of the decreased electron density on the anilinic nitrogen. KI-catalyzed oxidations of aminals to quinazolinones Different conditions for the direct catalytic oxidation of aminals to quinazolinones

• ion. However, the major product from this reaction was identified to be 31, the apparent product of iminium hydrolysis. Conclusion We have demonstrated that quinazoline alkaloids and their analogues can be synthesized from aminals by using Cu(OAc)2/O2/AcOH and KI/TBHP catalyst systems. The use of

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• ester 1 is treated with KI/I2 in H2O/CH2Cl2, which affords iodooxazinone derivative 2 stereo- and regioselectively (Scheme 1, Figure 1). Next, compound 2 is transformed to 3 by amide N-Boc protection with Boc2O and 4-dimethylaminopyridine (DMAP) in THF. Removal of the iodine from the cyclohexane

• regio- and stereoselective iodooxazine formation with KI/I2 to give compound 11 (Scheme 3). N-Protection of 11, followed by reductive deiodination, proceeded via 12 (Figure 3) to afford ester 13. Opening of the heterocyclic ring with NaOEt in EtOH at 0 °C furnished 4-hydroxylated amino ester 14, a

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• about reaction products is limited by the obscure structure of the real reaction product. In fact the reaction of pyridinium salt 2a with cyclic 1,3-diketones in the presence of either K2CO3 or DIPEA/KI yields an orange precipitate in acetonitrile. Redissolved in DMSO-d6, this precipitate gave rise to

• is quickly decomposed by silica gel liberating the desired product 3a or 6a, which was finally eluted from silica. The formation of a precipitate must be a driving force of the reaction promoted by DIPEA/KI (see Supporting Information File 2, thermodynamic analysis). The reaction starts with 1,3

Synthesis of guanidinium–sulfonimide ion pairs: towards novel ionic liquid crystals

• Martin Butschies,
• Manuel M. Neidhardt,
• Markus Mansueto,
• Sabine Laschat and
• Stefan Tussetschläger

Beilstein J. Org. Chem. 2013, 9, 1093–1101, doi:10.3762/bjoc.9.121

• salt metathesis are fulfilled. The known guanidinium chloride 7∙Cl [42] was treated with MeI in the presence of K2CO3 to afford the N-methylated guanidinium iodide 8∙I (Scheme 3) [38][39]. However, this intermediate did not allow a salt metathesis, because the resulting KI is highly soluble in MeCN

• % yield, respectively. In comparison the guanidinium iodide 7∙I was obtained in 94% yield by heating 7∙Cl with KI in MeCN under reflux (Scheme 3). The mesomorphic properties of ion pairs 2,3 and guanidinium halides 7∙I, 7∙Cl, 8∙I were studied by differential scanning calorimetry (DSC) and polarizing

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• , have been widely reported as Aβ-imaging tracers (Scheme 2A). Structure–activity-relationship (SAR) studies on fluorinated chalcones 18a–l have shown that, in general, chalcones with tertiary amines in their structures demonstrate good affinity for Aβ plaques in in vitro models (Ki = 20–50 nM) (Table 1

• of other derivatives, was prepared through condensation of 4-iodoacetophenone (26) and indole-5-carboxaldehyde (27) to give 28, which was radiolabeled to give the target compound (Scheme 2D) [15]. The indolochalcone 21 showed good binding affinity for Aβ1-42 aggregates with a Ki < 10 nM. Replacement

• towards Aβ aggregates with Ki values ranging between 5.3 nM for 29a and 19.3 nM for 29c (Scheme 3A) [16]. SAR studies suggest that, as with chalcones, the tertiary amine in these flavones was important for binding and tracing Aβ aggregates in mouse models, as they consistently outperformed secondary and

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• -catalyzed reaction with a different aryl iodide to yield asymmetric diaryl sulfides. With this strategy we synthesized different sulfur compounds. Accordingly, a solution of benzene thiolate obtained from this methodology affords bis(phenyl)disulfide (51%) after oxidation by KI/I2, by subsequent

• corresponding alkyl halide (0.75 mmol, 1.5 equiv) or KI/I2 (1.5 mmol/0.51 mmol, 3/1.02 equiv) was then added and stirred for 20 min or 24 h, respectively. The work-up of the reactions was similar to that of Method A. For the synthesis of the asymmetric diaryl sulfide, after hydrolysis of the thioester, a second

• -step synthesis of sulfides. (a) KI/I2; (b) BrCH2Ph; (c) MeI; (d) 4-AnI, CuI/1,10-phenanthroline (10 and 20 mol %, respectively), 100 °C, 24 h. Screening of solvents for the CuI-catalyzed reaction of potassium thioacetate (1) with iodobenzene.a Screening of copper sources for the copper-catalyzed

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• : 461.0 [M + Na]+. 13-Iodo-1-phenyl-2,5,8,11-tetraoxatridecane (4b): The synthesis of 4b utilized a procedure reported for a related compound [16]. A mixture of KI (23.97 g, 144.4 mmol) and sulfonate ester 4a (21.11 g, 48.14 mmol) in 250 mL of acetone was heated under reflux for 18 h. After cooling to

A new family of four-ring bent-core nematic liquid crystals with highly polar transverse and end groups

• Kalpana Upadhyaya,
• Venkatesh Gude,
• Golam Mohiuddin and
• Rao V. S. Nandiraju

Beilstein J. Org. Chem. 2013, 9, 26–35, doi:10.3762/bjoc.9.4

• of 4-n-butyloxy-2-hydroxybenzaldehyde (Scheme 2), monoalkylation was performed by using a modification of the literature procedure to improve the product yield. 2,4-Dihydroxybenzaldehyde (4, 10 g, 72.4 mmol), 1-bromobutane (10.3 mL, 75 mmol), KHCO3 (6.30 g, 75 mmol) and KI (catalytic amount) were

• , EtOAc stirring, 48 h; ii. dry acetone, KHCO3, CnH2n+1Br (n = 4, 5, 6, 8, 16); KI, Δ, 48 h; iii. abs EtOH, AcOH, Δ, 6 h; iv. DCC, DMAP, DCM, stirring, 48 h. Phase-transition temperatures (°C) of the compounds 1a–1f, recorded for second heating (first row) and second cooling (second row) cycles at 10 °C

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• . Affinity values (Ki in nM) at human 5-HT2A and 5-HT2C receptors. All values represent mean and SEM from at least three independent experiments. Potency and percent max values for calcium release at 5-HT2A and 5-HT2C receptors. All values represent mean and SEM from at least three independent experiments

• . Affinity values (Ki in nM) at selected serotonin receptor isoforms. Supporting Information Supporting Information File 240: Experimental details for all new compounds as well as the pharmacological methods used to measure receptor affinity and functional activity. Acknowledgments This research was

The importance of the rotor in hydrazone-based molecular switches

• Xin Su,
• Timo Lessing and
• Ivan Aprahamian

Beilstein J. Org. Chem. 2012, 8, 872–876, doi:10.3762/bjoc.8.98

• equilibrium constant of the protonation step, KI is the equilibrium constant for the rotation process, and KS is the overall equilibrium constant for the switching reaction. The pKa of PPH-1 is actually log10KP, so KS also equals . From the above equations, it becomes clear that KS can be used as an index to

• will be higher than in PPH-5. Moreover, the ester group is a better H-bond acceptor than the acetyl group, which means that the protonated Z configuration of PPH-1 is more stable than that of PPH-5, resulting in a larger KI for PPH-1. Thus, it can be qualitatively deduced that PPH-1 has a larger KS

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• , analytical descriptions of new metabolites and copies of 1H and 13C NMR spectra. Supporting Information File 86: Analytical details and compound spectra. Acknowledgements This work was supported by the Deutsche Forschungsgemeinschaft (Grant Ki-397, 13-1) and the Fonds der Chemischen Industrie.

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT2B with a Ki value of 7.7 µM. Keywords: marine fungi; natural products; phthalides; polyketides; Introduction Phthalides are a class of structurally very diverse secondary metabolites with more than 180 naturally

• the serotonin receptor 5-HT2B with a Ki value of 7.7 µM. Results and Discussion The molecular formula of 1 was deduced by accurate mass measurement (HRMS–EI) to be C21H28O4, requiring eight degrees of unsaturation. The 13C NMR and DEPT135 spectra contained 21 carbon resonances, including six resulting

• serotonin receptors, and marilone B showed a specific antagonistic effect on the serotonin receptor 5-HT2B with a Ki value of 7.7 µM. Compounds 1–4 were further evaluated for antiviral activity, for inhibition of protein kinases and proteases, for growth inhibition of antibiotic-resistant Mycobacterium

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• the strong caesium carbonate base led to better results, which was attributed to a better solubility of the base along with a lower solubility of the generated CsI compared to KI salts, preventing an iodide-inhibition effect (Scheme 6). Moreover, copper iodide used as a cocatalyst was able to improve

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• conditions: i. NaBH4, EtOH, 1 h, 25 °C; ii. HBr/HOAc, 2 h, 25 °C, 38% (2 steps); iii. NaN3, EtOH, 4 h, reflux, 94%; iv. NH2OH·HCl, NEt3, EtOH, 1.5 h, 25 °C, 87%; v. PPh3, H2O/MeOH, 18 h, 25 °C, 80%. Synthesis of 3-((hydroxyimino)methyl)-1-(prop-2-ynyl)pyridinium bromide (6). Reagents and conditions: i. KI

Synthesis and oxidation of some azole-containing thioethers

• Andrei S. Potapov,
• Nina P. Chernova,
• Vladimir D. Ogorodnikov,
• Tatiana V. Petrenko and
• Andrei I. Khlebnikov

Beilstein J. Org. Chem. 2011, 7, 1526–1532, doi:10.3762/bjoc.7.179

• unsuitable for thioether functionalization. Using a non-oxidative aqueous I2/KI system [19] readily yields the corresponding diiodo-thioethers 11 and 12 (Scheme 4). In order to explore the reasons for the different reactivity of thioethers 3 and 5 in the oxidation reaction, we carried out DFT calculations of

A practical microreactor for electrochemistry in flow

• Kevin Watts,
• William Gattrell and
• Thomas Wirth

Beilstein J. Org. Chem. 2011, 7, 1108–1114, doi:10.3762/bjoc.7.127

• solvent was then removed, water was added (3 mL) and the iodide was precipitated by addition of KI (166 mg, 1 mmol) to give the diaryliodonium salts 11. Di-p-tolyliodonium iodide (11a) [24] Collection of 3 mL, yield: 100 mg (72%); colourless solid; mp 162–164 °C; 1H NMR (400 MHz, CDCl3) δ 2.27 (s, 6H

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• situ from the reaction of 2.0 equivalents of indium with 3.0 equivalents of substituted propargyl bromide in the presence of 3.0 equivalents of KI. The best solvent from those that were screened (DMF, THF, C6H6, and C6H5CH3) was found to be DMF. Because further functionalization of the allene group

Synthesis of chiral mono(N-heterocyclic carbene) palladium and gold complexes with a 1,1'-biphenyl scaffold and their applications in catalysis

• Lian-jun Liu,
• Feijun Wang,
• Wenfeng Wang,
• Mei-xin Zhao and
• Min Shi

Beilstein J. Org. Chem. 2011, 7, 555–564, doi:10.3762/bjoc.7.64

• (Me) 2 on heating in THF for 8 h in the presence of KI and t-BuOK to give the expected chiral NHC–Au(I) complex (S)-6a in 65% yield (Scheme 3). Its structure was also confirmed by X-ray diffraction (Figure 4) [56]. It was found that the Au–carbene distance is 2.036 Å which is consistent with other

• salt (S)-5b in quantitative yield. Benzimidazolium salt (S)-5b was then complexed with Au (I) as described above for (S)-6a (AuCl·S(Me)2 in the presence of KI and t-BuOK in THF for 8 h) to produce the expected chiral NHC–Au(I) complex (S)-6b in 32% yield. For the preparation of (S)-6c, (S)-6,6

• ); Anal. Calcd. for C27H28IN3O3Pd requires: C, 47.98; H, 4.18; N, 6.22%. Found: C27H28IN3O3Pd, C 47.78, H 4.68, N 5.78%. Synthesis of NHC–Au(I) complex (S)-6a Compound (S)-5a (105.8 mg, 0.2 mmol) and AuCl·S(Me)2 (58.8 mg, 0.2 mmol), KI (49.8 mg, 0.3 mmol) t-BuOK (56 mg, 0.5 mmol) were heated under reflux

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

Synthesis of glycoconjugate fragments of mycobacterial phosphatidylinositol mannosides and lipomannan

• Benjamin Cao,
• Jonathan M. White and
• Spencer J. Williams

Beilstein J. Org. Chem. 2011, 7, 369–377, doi:10.3762/bjoc.7.47

• the glycosidic linkage. For α-mannosylation of primary and secondary alcohols, the mannosyl donors 16 [38] and 17 were used. Treatment of glycosyl bromide 11 with NaBH4/KI in MeCN [39] afforded the crystalline 1,2-O-benzylidene acetal 18 as a single diastereoisomer in quantitative yield (Scheme 3

Identification and synthesis of impurities formed during sertindole preparation

• I. V. Sunil Kumar,
• G. S. R. Anjaneyulu and
• V. Hima Bindu

Beilstein J. Org. Chem. 2011, 7, 29–33, doi:10.3762/bjoc.7.5

• sertindole. Sertindole (1), process related impurities and metabolites. Reagents and conditions: i) K2CO3, CuBr, ethylenediamine, DMF 130–135 °C; ii) CH3COOH, CF3COOH, 100–110 °C; iii) PtO2/H2, methanol, 30–35 °C; iv) K2CO3, KI, methylisobutyl ketone (MIBK),110–115 °C. Reagents, conditions (and yields): i

• ) (a) pH adjusted to 6; (b) Pd/C, HCOONH4, AcOH, MeOH, reflux (77.6%); ii) 16, K2CO3, KI, MIBK, reflux (44.5%). Reagents, conditions (and yields): i) 16, K2CO3, KI, MIBK, reflux (73.9%). Reagents, conditions (and yields): i) Cs2CO3, DMF, 130–135 °C; ii) 14, CH3COOH, CF3COOH, 100–105 °C (43.4% from 11

• ); iii) (a) pH adjusted to 6–7; (b) H2, PtO2, MeOH, AcOH, 30–35 °C; (c) crystallization (24.7%); iv) 16, K2CO3, KI, MIBK, reflux (65% yield). Reagents, conditions (and yields): i) (a) pH adjusted to 6–7; (b) H2, PtO2, MeOH, AcOH, 30–35 °C (73% yield); ii) 16, K2CO3, KI, MIBK, reflux (52%). Reagents