A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

• Takahiro Furune,
• Naoko Ikuta,
• Yoshiyuki Ishida,
• Hinako Okamoto,
• Daisuke Nakata,
• Keiji Terao and
• Norihiro Sakamoto

Beilstein J. Org. Chem. 2014, 10, 2827–2835, doi:10.3762/bjoc.10.300

• cholesterol addition, and was derived from impurity of the lecithin reagent used. The cholesterol concentration dissolved within the FeSSIF increased with cholesterol addition. The addition of 1 or 2% α-CD into the FeSSIF did not affect the cholesterol dissolution in the FeSSIF but the addition of 3% α-CD

Copolymerization and terpolymerization of carbon dioxide/propylene oxide/phthalic anhydride using a (salen)Co(III) complex tethering four quaternary ammonium salts

• Jong Yeob Jeon,
• Seong Chan Eo,
• Jobi Kodiyan Varghese and
• Bun Yeoul Lee

Beilstein J. Org. Chem. 2014, 10, 1787–1795, doi:10.3762/bjoc.10.187

• polymerizations showed immortal polymerization character; therefore, the molecular weights were determined by the activity (g/mol-1) and the number of chain-growing sites per 1 [anions in 1 (5) + water (present as impurity) + ethanol (deliberately fed)], and the molecular weight distributions were narrow (Mw/Mn

• -weight mode was always twice that in the low-molecular-weight mode. The chains in the high-molecular-weight mode were attributed to those grown biaxially from water, which was present as an impurity, while those in the low-molecular-weight mode were grown from the nitrate and acetate anions in 1. The

• water molecules per 1 present as an impurity (8, 10, 8, and 4, respectively). The portion of the high-molecular-weight mode (that is, the portion of chains grown from water molecules) relative to the portion of the low-molecular-weight mode decreased in the GPC curves in the order of entries 2, 3, and 4

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

• 11 using Ley–Griffith oxidation, its reaction with 12, using LiHMDS as the base, afforded 13 in 75% yield, though as a 1:1 mixture of 2E,4E- and 2E,4Z-isomers. Moreover, the 1H NMR spectra indicated the presence of an impurity, which appeared as a multiplet between 5.00 and 5.45 ppm. Although minimal

• amounts of 2E,4Z-13 could be isolated, 2E,4E-13 was inseparable from this impurity. We decided to continue the synthesis with impure 13, which was reduced with DIBALH at low temperature to give crude 1 in 96% yield. TLC analysis indicated the presence of two major, separable, products. Purification by

• ]. Next to ~60% of the desired product, around 40% of the mass balance consisted of an inseparable impurity. 1H NMR spectroscopy again showed a set of multiplets between 4.95–5.00 ppm. Although repeated recrystallization of commercial reagent 14 reduced the impurity to 6%, pure 15 could not be obtained

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• storage in a ratio of ~ 3:2 with acid 1 as an impurity. The low stability of all three esters 2–4 can be attributed to the lability of the O–C ester bond, resulting from the electron-withdrawing effect of the CF3 group attached to phosphorus, therefore esters 2, 3 and 4 were used in the syntheses only

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• -ketoamide 9 (Scheme 2). It was possible to limit the formation of benzamide impurity 17 in the reaction to <15% (Table 1); however, we were unable to avoid the formation of 17 under any of the attempted reaction conditions (Scheme 3). The α-ketoamide 9 thus obtained by the oxidative amidation methodology

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• carbamate protected amino acid derivatives 3 (remaining as impurity in the isolated products 2), quantitative benzylation (1→I) was ensured by successive addition of three portions of benzaldehyde/NaBH4 (Quitt´s procedure [61] → two portions) and by maintaining the pH at a value of 10–11. The extractive

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• used over numerous runs without catalysts degradation, metal leaching or reduction in activity through impurity deposition [12][15]. Virtually all forms of palladium have been used as catalysts for the Heck reaction. A wide array of combinations depending on the components of the catalytic system is

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• asymmetric access to the advanced-stage intermediate 7 under precise stereochemical control as well as for circumventing the purification problems related to the diastereomeric impurity in this product. Conclusion We have described a new synthetic approach to (+)-batzellaside B from L-pyroglutamic acid

Synthesis of compounds related to the anti-migraine drug eletriptan hydrobromide

• Suri Babu Madasu,
• Nagaji Ambabhai Vekariya,
• M. N. V. D. Hari Kiran,
• Badarinadh Gupta,
• Aminul Islam,
• Paul S. Douglas and
• Korupolu Raghu Babu

Beilstein J. Org. Chem. 2012, 8, 1400–1405, doi:10.3762/bjoc.8.162

• , control may be possible. The related compounds (impurities) of eletriptan hydrobromide were synthesized and characterized by using various spectroscopic techniques, and further confirmed by co-injection in HPLC. Results and Discussion The eletriptan dimer impurity 2 is observed at 0.3–0.5% during the

• basic hydrolysis of enesulfone derivative 12 and the impurity level is reduced to less than 0.20% during the isolation and purification process [12]. It is necessary to remove the impurity at this stage or control the formation during basic hydrolysis. Otherwise, the reduction rate of this impurity in

• later stages is low. Impurity 2 was prepared by the dimerization of desacetyl-ensulfone derivative 13 using a strong base, such as sodium hydride, under Michael addition reaction conditions in an anhydrous medium (Scheme 2). This impurity can be controlled by using hydrous conditions during the

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• chemoselective) reactions have been reported [1][2][3]. However, one drawback of this approach is the requirement of the removal of the metal impurity from the products. An organocatalytic approach is attractive in this sense as it is metal-free, cost-effective, and favoured by the pharmaceutical industry for

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• -trifluoromethylphenyl)acrylic acid (9) in 90% yield [13]. The acid 9 was hydrogenated in the presence of 10% Pd/C catalyst in aqueous sodium hydroxide solution at ambient temperature, initially under 4.0 bar hydrogen overpressure to get 3-(3-trifluoromethylphenyl)propionic acid (10) in 98% yield. The desfluoro impurity

• 14 (around 8.2%, HPLC) was also detected (Scheme 4). Initially, 14 was reported in the literature [5] as a carryover impurity from bromo derivative 5 and from hydrogenation of 9 in methanol. The latter also lead to the reduction of the phenyl ring concomitant with double bond reduction. To reduce the

• formation of 14, the reduction was tried to be carried out with 5% Pd/C and simply bubbling hydrogen gas into the reaction mixture at room temperature, and also by reducing the proportion of the catalyst (Table 1). The impurity formation was observed even at low catalyst loading. As a result, the impurity

Palladium-catalyzed substitution of (coumarinyl)methyl acetates with C-, N-, and S-nucleophiles

• Kalicharan Chattopadhyay,
• Erik Fenster,
• Alexander J. Grenning and
• Jon A. Tunge

Beilstein J. Org. Chem. 2012, 8, 1200–1207, doi:10.3762/bjoc.8.133

• addition, the product was determined to contain 2% PPh3 impurity. Thus, it was concluded that the entire library should be purified by mass-directed fractionation to ensure high-quality compounds for biological screening. Regarding the library, coumarins and amines were chosen with diverse structures and

Synthesis of functionalized macrocyclic derivatives of trioxabicyclo[3.3.0]nonadiene

• Sabine Leber,
• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2012, 8, 738–743, doi:10.3762/bjoc.8.83

• reduced nitro derivative 12 as an impurity (Scheme 3). A remarkable reaction is the ready conversion of macrocyclic as well as open-chain bisdioxine derivatives to 2,4,6,8-tetraoxaadamantanes on acid hydrolysis [4][7][15]. This transformation was also achieved with the dinitro compound 8, which yielded

• moment; LC–MS m/z: 1287.5 [M + H]+. The LC–MS indicated the presence of the mono-amine 12 as an impurity, m/z: 1317.5 [M + H]+. Tetraoxaadamantane 14: To a solution of 50 mg of dinitro compound 8 in 1 mL of CH2Cl2 and 1 mL of glacial acetic acid was added 55 µL of conc. HCl, and the resulting mixture was

Discovery of practical production processes for arylsulfur pentafluorides and their higher homologues, bis- and tris(sulfur pentafluorides): Beginning of a new era of “super-trifluoromethyl” arene chemistry and its industry

• Teruo Umemoto,
• Lloyd M. Garrick and
• Norimichi Saito

Beilstein J. Org. Chem. 2012, 8, 461–471, doi:10.3762/bjoc.8.53

• . The method of run 7 using both KHF2 and benzene as additives provided product 3b with 99% purity, as the formation of impurity 3b·Cl was completely suppressed. It is likely that the SF4Cl part of 2b acts as a chlorinating agent toward 3b, or another 2b and benzene, under the strong acidic conditions

Improved syntheses of high hole mobility phthalocyanines: A case of steric assistance in the cyclo-oligomerisation of phthalonitriles

• Daniel J. Tate,
• Rémi Anémian,
• Richard J. Bushby,
• Suwat Nanan,
• Stuart L. Warriner and
• and Benjamin J. Whitaker

Beilstein J. Org. Chem. 2012, 8, 120–128, doi:10.3762/bjoc.8.14

• impurities, the phthalocyanine 7f was subjected to ICP-MS trace metal impurity analysis, but levels of transition metal impurities were found to be below the IPC-MS detection limit (ppb). The most likely explanation for the effect of these branched-chain substituents on the yields of these reactions is shown

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• (Table 1, entry 7) to completion, it was found that heating the monolith resulted in the production of an impurity, at 29.7% conversion by 1H NMR (with 64.5% conversion to the bromide). This was identified as 1-(chloromethyl)-4-iodobenzene, i.e., the starting material underwent chlorination rather than

• bromination. The two halogenated products could not be separated by flash column chromatography. Interestingly this impurity was also observed in small amounts when a loaded monolith was stored for prolonged periods at room temperature in the presence of dichloromethane. The Appel reaction using 4-iodobenzyl

• monolith, implying that the source of the chloride was through exchange with the dichloromethane solvent. From our initial screens, dichloromethane was found to be the optimum solvent for monolith loading and the bromination reactions. As this impurity was only observed at elevated temperatures or with

Photoinduced electron-transfer chemistry of the bielectrophoric N-phthaloyl derivatives of the amino acids tyrosine, histidine and tryptophan

• Axel G. Griesbeck,
• Jörg Neudörfl and
• Alan de Kiff

Beilstein J. Org. Chem. 2011, 7, 518–524, doi:10.3762/bjoc.7.60

• by X-ray diffraction analysis (Figure 2) [11], has also been described in literature as a yellow compound [12][13]. The color is not the consequence of any impurity and did not vanish after several recrystallizations and, more importantly, was also observed for the methyl ester and the

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

• . Keywords: impurity profile; related substances; sertindole; Introduction The safety of a drug product is not only dependent on the toxicological properties of the active drug substance (or API), but also on the impurities formed during the various chemical transformations. Therefore, identification

• difficult for the organic chemist who must then design a synthesis, which is time consuming. The development of a drug substance is incomplete without the identification of an impurity profile involved in the process. Furthermore, it is not mandatory to design synthetic routes for the impurities. Thus, in

• -chloroethyl)imidazolidinone (16) in the presence of a base gives sertindole (1). During the laboratory optimization of sertindole (1), many process related impurities were identified. The guidelines recommended by ICH state that the acceptable levels for a known and unknown compound (impurity) in the drug

Halide exchanged Hoveyda-type complexes in olefin metathesis

• Julia Wappel,
• César A. Urbina-Blanco,
• Mudassar Abbas,
• Jörg H. Albering,
• Robert Saf,
• Steven P. Nolan and
• Christian Slugovc

Beilstein J. Org. Chem. 2010, 6, 1091–1098, doi:10.3762/bjoc.6.125

• necessary to obtain 2 or 3 in 90–92% yield and 95–98 % purity. Efforts to further shift the equilibrium towards 2 or 3 have so far proved unsuccessful. The impurity, which could not be separated by recrystallisation or column chromatography, was identified as the “mixed halogen” compound and as revealed by

Synthesis of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide – a tailor-made photoinitiator for dental adhesives

• Norbert Moszner,
• Iris Lamparth,
• Jörg Angermann,
• Urs Karl Fischer,
• Frank Zeuner,
• Thorsten Bock,
• Robert Liska and
• Volker Rheinberger

Beilstein J. Org. Chem. 2010, 6, No. 26, doi:10.3762/bjoc.6.26

• with a molecular weight of 867 g/mol (Scheme 5) was formed in all cases as the main impurity in amounts of 0.5–5%. The structure of this compound was also clearly confirmed by the 13C and 1H NMR spectroscopic measurements of a WBAPO sample that specifically contained about 70% of this side product. The

• of 2 under formation of 4. Synthesis of WBAPO starting from P,P-dichlorophenylphosphine and 2. Structure of the main impurity in isolated WBAPO. Shear bond strength (SBS, MPa) on dentin of experimental aqueous SEAsa measured after storage of different SEAs at 42 °C.

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

8-epi-Salvinorin B: crystal structure and affinity at the κ opioid receptor

• Thomas A. Munro,
• Katharine K. Duncan,
• Richard J. Staples,
• Wei Xu,
• Lee-Yuan Liu-Chen,
• Cécile Béguin,
• William A. Carlezon Jr. and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2007, 3, No. 1, doi:10.1186/1860-5397-3-1

• apparent above baseline noise. We separated 4a and 4b with difficulty by repeated chromatography in EtOAc/hexanes. The sample of 4a contained traces of an inseparable impurity, which if active might artificially elevate the apparent binding affinity. Since the sample showed no affinity, however, this