Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• ). TDDFT-ECD calculation was proved an efficient method to determine the absolute configuration of separated stereoisomers of bioactive synthetic [19] and natural derivatives [20][21] on the basis of their HPLC-ECD spectra. For the configurational assignment of the separated enantiomers, TDDFT-ECD

Phosphinocyclodextrins as confining units for catalytic metal centres. Applications to carbon–carbon bond forming reactions

• Matthieu Jouffroy,
• Rafael Gramage-Doria,
• David Sémeril,
• Dominique Armspach,
• Dominique Matt,
• Werner Oberhauser and
• Loïc Toupet

Beilstein J. Org. Chem. 2014, 10, 2388–2405, doi:10.3762/bjoc.10.249

• trans (strong CO IR band at 1985 cm−1 [55][56]) configured. Remarkably, the same ratio of stereoisomers was obtained when rhodium complex 13 (see Scheme 6) was treated with LiCl under CO (1 atm). When the reaction between HUGPHOS-2 and [RhCl(CO)2]2 was repeated, but applying a 1:1 instead of 1:0.5

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• cleavage of carbobicycle-fused 2-isoxazolines converts both exo- and endo stereoisomers of 8 into the corresponding single isomer of cyclopentene 9 (Table 1) [20]. Since then, we have been interested in the outcomes of cleavage reactions of 2-isoxazolines fused to heterobicyclic compounds 10 or 11, which

Building complex carbon skeletons with ethynyl[2.2]paracyclophanes

• Ina Dix,
• Lidija Bondarenko,
• Peter G. Jones,
• Thomas Oeser and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 2013–2020, doi:10.3762/bjoc.10.209

• diastereomers are generated (as expected) by the oxidative dimerization of the mono ethynyl derivative [9], but assignment of the various spectra to specific stereoisomers remains an open question, and will only be possible after the resolution of the 4-ethynyl[2.2]paracyclophane, determination of its absolute

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• dioxolane C-2 (ratios close to 1:1). The preparation of syn-1,2-oxazine 4 was achieved in good yields ranging from 67–77% by stereocontrolled addition of lithiated (trimethylsilyl)ethoxyallene 9 to (Z)-nitrone 6 at −78 °C (Scheme 3). Although the formation of four stereoisomers is possible only two were

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

• , the uridine example is shown) [114]. The coupling products 98 were obtained as (Z)-stereoisomers for studies related to the drug discovery against the hepatitis C virus. The methodology shown in Scheme 40 [114] was further elaborated on reactions of polyfunctional iodide 99 with four equivalents of

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• ; 10,11-cis-silybin; isomerization; silibinin; silybin; silymarin; Introduction The flavonolignan silybin (alternative name silibinin), occurring in the fruits of Silybum marianum (milk thistle), consists of two stereoisomers – silybin A (1a) and B (1b) – in a ca. 1:1 ratio (Figure 1). Their absolute

• (or 10 from 1b) on silica gel was not feasible, analogous to the preparative separation of silybin stereoisomers 1a and 1b (Figure 1), which was a challenge for several decades. It was accomplished as the separation of the respective silybin glycosides for the first time [13][14], later by HPLC [3

• -glucopyranoside 6''-gallate, Figure 6) was subjected to both, basic and acidic hydrolysis during its structure elucidation. However, under these conditions four stereoisomers of the original aglycon (2R,3R)-taxifolin were formed. Base-catalyzed isomerization of another taxifolin glycoside, (2R,3R)-2,3

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• an initial approach we aimed at the synthesis of a library of stereoisomers of A (Figure 2). The commercially available racemic anti-dimethyl 2,4-dimethylglutarate (1) was reduced to the corresponding racemate of 2,4-dimethylpentan-1,5-diol (2) [13], which was further transformed to the monosilyl

• position 2 underwent ca. 6% epimerization to yield 7 as a mixture of 4 stereoisomers. The synthesis of 2,6,8,12-tetramethyltrideca-2,4-diene (8) was completed by Wittig reaction using (3-methylbut-2-en-1-yl)triphenylphosphonium bromide [15]. As expected, the obtained mixture of all possible stereoisomers

• with malonate and another methylmalonate (including deoxygenation steps) seemed to be plausible [16]. These biogenetic considerations excluded methyl groups at positions 9 and 11. To prepare a mixture of all stereoisomers of 14, we again used 2 as the starting material (Figure 2). Monobenzylation to 9

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• by avoiding traditional purification methods such as chromatography or recrystallization. The pure products, often pure stereoisomers, can be easily obtained by washing the crude products with common solvents or co-solvents [22][23][24][25]. Our GAP concept was attributed to the study of a series of

Synthesis of fluorescent (benzyloxycarbonylamino)(aryl)methylphosphonates

• Michał Górny vel Górniak,
• Anna Czernicka,
• Piotr Młynarz,
• Waldemar Balcerzak and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 741–745, doi:10.3762/bjoc.10.68

• chromatography, a significant enrichment in one of the diastereomers had been observed. For example, compound 7b obtained as a 55:45 molar mixture of stereoisomers after purification by means of chromatography was obtained as 85:15 molar mixture. The approach to obtain mixed esters bearing two aromatic moieties

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• preferentially accepts the 2D,3D-configured precursor, if all four potential stereoisomers of 3-hydroxy-2-methyl-SNAc-pentanoate model substrates are presented [7]. A commonly accepted model suggests that DHs from PKS I systems catalyze the removal of water by syn-dehydration and that a 2D,3D-configured

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• flexible and fixed acceptor moieties. DFT-computed energy differences of the stereoisomers of 2Z,4Z-8a and 2Z,4E-8a. DFT-computed energy differences of the stereoisomers of 10a and 10h. DFT-computed (B3LYP functional, 6-31G* basis set) HOMO (left) and LUMO (right) of merocyanine 8a. Absorption and emission

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• -protected [(dppp)Pd]2+ and [(dppp)Pt]2+ ions. The self-assembly process of the racemic ligand preferably occurs in a narcissistic self-recognising manner. Hence, a mixture of all three possible stereoisomers [(dppp)2M2{(R)-L}2](OTf)4, [(dppp)2M2{(S)-L}2](OTf)4, and [(dppp)2M2{(R)-L}{(S)-L}](OTf)4 was

• (Figure 2a,b). In principle, three stereoisomers of the dinuclear metallosupramolecular rhombi can form from racemic ligands upon coordination to [(dppp)Pd(OTf)2] or [(dppp)Pt(OTf)2] – a racemic mixture of two enantiomeric homochiral assemblies and an achiral heterochiral complex. These are expected to

• heterochiral one in both cases – the palladium and the platinum complexes and independent of the solvents we used. This corresponds to an amplification of the homochiral stereoisomers via self-recognition by a factor of approximately three. Although these NMR spectra already provide a very good proof for the

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

• Abstract A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• involves a sequential double isocyanide incorporation into the C=N bond. The final step is a nucleophilic 4-exo-dig cyclization, and the anti addition modes likely lead to less stable stereoisomers which spontaneously isomerize to the observed compounds. Furthermore, we have determined the scope of the

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• ). Over 200 conformers were found for each of the stereoisomers for 2a–h (see Experimental), and their geometries were optimized at the DFT theoretical level by using the MPW1PW91 functional and 6-31G(d) [26] basis set (Gaussian 09 Software Package [27]). From the DFT-optimized geometries interproton

• -calculated interproton distances for 2a,b,e,f differed by more than 0.03 Å (≈ 1%) from each other. The data reported in Table 3 clearly show that the diastereoisomer 2b represents the best fit with the experimentally derived distances (MAE 4.1% and standard deviation (STD) 5.0%). The stereoisomers 2a, 2e and

• 2f poorly agree with the NOE-derived distances. The maximum error shown by the calculated distances for 2b is 9.4%, whereas the other stereoisomers have at least three calculated distances with an associated error higher than 10%. The largest errors (>10%) are relative to protons around the

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

• I. Wayan Mudianta,
• Victoria L. Challinor,
• Anne E. Winters,
• Karen L. Cheney,
• James J. De Voss and
• Mary J. Garson

Beilstein J. Org. Chem. 2013, 9, 2925–2933, doi:10.3762/bjoc.9.329

• individual stereoisomers (see below). The 3:1 ratio of E/Z-isomers was confirmed via analytical HPLC. In principle, the rearrangement of 6 could afford either [1,2]-rearranged products (e.g. 7a/b or 8) or [2,3]-rearranged products such as 9 or 10 depending on which site adjacent to the ether oxygen is

Novel supramolecular affinity materials based on (−)-isosteviol as molecular templates

• Christina Lohoelter,
• Malte Brutschy,
• Daniel Lubczyk and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2013, 9, 2821–2833, doi:10.3762/bjoc.9.317

• ) provides an open side to access the concave regime. As anticipated, two stereoisomers are formed in this condensation reaction of 5b with 4. After separation via column chromatography, these products were identified as the all-syn- and anti,anti,syn-isomers of the desired product 8, which were obtained in

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• enantiomers 29a and 29b was excellent, with over 6 minutes separating the stereoisomers in the chromatograms. Due to the robust nature of the dibenzoylation chemistry and the excellent chromatograms produced, the derivatisation/chiral HPLC assay was used routinely. However, direct measurement of the ee's of

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• Volker M. Schmiedel Stefano Stefani Hans-Ulrich Reissig Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, D-14195 Berlin, Germany 10.3762/bjoc.9.291 Abstract Herein we present the synthesis of the anhydrophytosphingosine jaspine B and three of its stereoisomers using a

• therefore leads to a stereodivergent approach to the natural product and its enantiomer. The gold-catalyzed 5-endo-cyclization affords the corresponding dihydrofurans, which after separation, azidation of the enol ether moiety and two subsequent reduction steps give the natural product and its stereoisomers

• synthesis of stereoisomers of the natural product [4][12][16][17][19][26][27][28] because these compounds also showed comparable biological activities [4][5]. During our current studies on the synthesis of highly functionalized heterocycles utilizing alkoxyallenes as versatile C3-building blocks we chose

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• subsequent Friedel–Crafts reaction (Scheme 6). Both compounds were isolated as single stereoisomers with a high overall yield [43]. In this case, the 5-exo pathway was more competitive compared to the result of model substrate 1a, probably due to the Thorpe–Ingold-type effect caused by the methyl group at

Flow synthesis of phenylserine using threonine aldolase immobilized on Eupergit support

• Jagdish D. Tibhe,
• Hui Fu,
• Timothy Noël,
• Qi Wang,
• Jan Meuldijk and
• Volker Hessel

Beilstein J. Org. Chem. 2013, 9, 2168–2179, doi:10.3762/bjoc.9.254

• four isomers is depicted in Figure 13. The correct elution of the different stereoisomers was elucidated by injecting pure sample of each compound and comparison with literature [43][44][45]. In all experiments, 20% of diastereomeric excess of phenylserine was observed and a >99% enantiomeric excess

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

• Sylvestre Bachollet,
• Kimitada Terao,
• Shin Aida,
• Yasuhiro Nishiyama,
• Kiyomi Kakiuchi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2013, 9, 2015–2021, doi:10.3762/bjoc.9.237

• acetone and irradiation with UVB light) gave an incomplete conversion of approximately 60%. A complex mixture of various stereoisomers of 3 and several unknown byproducts was obtained, which could not be separated satisfactory. Direct irradiation conditions were thus chosen for all further investigations

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• stereoisomers of Ile are less hydrophobic than Aha. F6Leu is similar to Aha in hydrophobicity, while exhibiting a much larger volume. In a free energy perturbation study, the hydration energy of F6Leu was shown to be 1.1 kcal/mol higher than that of leucine [29]. This, together with our previous and new

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• were published [2][5][6][7][8] as well as numerous reports dedicated to derivatives and stereoisomers [9][10][11][12][13][14][15][16][17][18][19][20]. Examination of structure–activity relationship (SAR) revealed a loss of antibiotic activity upon shifting of the methyl group to different positions