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

• the possibility of obtaining 2 via intramolecular epoxide ring-opening of 7 (Scheme 1, method 2). Consequently, an alternative pathway involving the Mitsunobu inversion of 9 (obtained by intramolecular epoxide ring-opening of 8 which is the enantiomer of 6) has been followed to obtain 2 (Scheme 1

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

• process. The stereochemistry of the adduct can be simply switched to the opposite enantiomer, by using the enantiomeric supported catalyst PS–(R)-pybox–calcium chloride. The enantiomeric excess of the products was about 96%. Two more steps consisting in a Pd-catalyzed hydrogenation reaction and a

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• the final polyketide products could arise by judicious choice by the PKS AT domains of one or the other enantiomer. The first information on extender unit selection in polyketide biosynthesis was provided in the mid-1980s via feeding of isotopically-labeled precursors to whole cells of the

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

• absorbed in blood plasma more quickly than the undissociated acid [11]. In the following, we will refer to the undissociated acid as IbuH and to the sodium salt as IbuNa. For both IbuH and IbuNa, the desired pharmacological effects are due to the S-enantiomer. Nevertheless, the commercially available drug

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

• Cira Mollings Puentes and
• Thomas J. Wenzel

Beilstein J. Org. Chem. 2017, 13, 43–53, doi:10.3762/bjoc.13.6

• observed with the phosphated cyclodextrins. Keywords: chiral; chiral differentiation; cyclodextrin; enantiomer; enantiomeric purity; NMR; Introduction Chiral NMR solvating agents are commonly used for determining enantiomeric purity. In some cases, these compounds cause reproducible perturbations in

• enantiomer of the substrate with the higher association constant has a higher proportion complexed with the P-CD at 5 mM than the substrate enantiomer with the lower association constant. Therefore, resonances of the substrate with the higher association constant are more perturbed in the NMR spectrum. At

• higher concentrations of P-CD (10 or 20 mM), also a higher proportion of the enantiomer with the lower association constant binds to the P-CD, thus enhancing perturbations in the NMR spectrum of this enantiomer and thereby diminishing the extent of enantiomeric differentiation. In some cases, the

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• its enantiomer (Table 2, entry 3). Therefore, the one-pot two-steps cyclization reaction was investigated with different amino ester/amine combinations (H-AA-OMe/R2-NH2) and comparative experiments using dry- or wet-grinding with PEGs (Mw = 2000 and 3400, 450 mg mmol−1) were also performed (Table 3

Characterization of the synthetic cannabinoid MDMB-CHMCZCA

• Carina Weber,
• Stefan Pusch,
• Dieter Schollmeyer,
• Sascha Münster-Müller,
• Michael Pütz and
• Till Opatz

Beilstein J. Org. Chem. 2016, 12, 2808–2815, doi:10.3762/bjoc.12.279

• TD-DFT; however, the experimental positive/negative sequence is inverted in the range from 200 to 230 nm. Overall, this yields an enantiomeric similarity index (ESI) [16] of only 34% in favor of the S-enantiomer, therefore not enabling a reliable assignment of the absolute configuration. The

• seven other samples (Table 1); small amounts of the (R)-enantiomer could only be detected in the case of test purchase 3. Conclusion A pure sample of the new synthetic cannabinoid MDMB-CHMCZCA (3), purchased in an online RC shop, was characterized and the absolute configuration was determined to be (S

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• ’, respectively). Crystal packing is a racemate due to the centrosymmetric symmetry and in the picture the choice of the enantiomer is arbitrary. C: light blue, H: white, O: red, N: magenta. Probability of the ORTEP ellipsoids is set to 50%, whereas H size is arbitrary. Three-dimensional plots of TSs of reaction

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• reported for (Z)-tetradec-5-en-13-olide (1) by Millar et al. [11], exhibiting a molecular ion at m/z 224. This macrolide, called cucujolide III, is used by the flat grain beetle Cryptolestes pusillus as pure (S)-enantiomer and by C. turcicus as a 33:67 R/S mixture [12], and acts as a synergist to the

• opted to synthesize 2 as well. To allow later enantiomer determination of A, an enantioselective synthetic strategy was followed. Several synthetic routes for the synthesis of 1 have been reported [16][17][18][19][20]. These syntheses were performed before the advent of ring-closing metathesis (RCM

• [21]. The synthesis of (R)-2 using RCM as key step is shown in Scheme 1. Enantiomerically pure 1,2-epoxyhex-5-ene (6) was obtained by Jacobsen hydrolytic kinetic resolution on commercially available 6 (Scheme 1) [22][23]. Surprisingly, the yield of 69% of the (R)-enantiomer was higher than the

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• reaction yielded 3a with good enantiomeric ratio (Table 3, entry 1). In the presence of the other enantiomer of L2, (S,S)-PhPyBox, the reaction afforded good er. When N-(2-methhoxyphenyl)tetrahydroisoquinoline was used, the corresponding enantiomer was obtained with similar enantioselectivity (Table 3

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• either enantiomer of the α-terpinyl cation (6, Scheme 1). Isotopic labelling experiments currently experience a revival [15] and are a very powerful method to follow the enzyme mechanisms of terpene cyclases [16][17][18][19][20][21][22][23][24] including the stereochemical courses of the cyclisation

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• trans-arrangement of the phosphoryl and n-hexyl substituents, the absolute configuration (2S,3R) should be ascribed to (+)-3 according to Cahn, Ingold, and Prelog rules [25][26]. As a consequence, the enantiomer (−)-3 has the absolute configuration (2R,3S). In the course of our investigations on the

Determination of the absolute stereostructure of a cyclic azobenzene from the crystal structure of the precursor containing a heavy element

• Reji Thomas and
• Nobuyuki Tamaoki

Beilstein J. Org. Chem. 2016, 12, 2211–2215, doi:10.3762/bjoc.12.212

• ; cyclic compound; enantiomer; stereostructure; X-ray crystal analysis; Introduction Chirality is a topic of fundamental importance in several branches of science [1][2][3][4][5]. Homochirality in nature was one of the most important challenges for researchers and the origin is still unsolved [6][7][8

• . Results and Discussion Figure 1 shows the schematic representation of experiments involved in the separation and reductive debromination of the enantiomer (E)-1B. The enantiomers of molecules (E)-1 and (E)-2 are previously reported as photocontrolled chiroptical switches for various nematic liquid

• [45]. In this study, we employ this enantiomer as a precursor for the determination of the absolute configuration of its reduced product, which is expected as one of the enantiomers of (E)-2. In order to characterize the reduced product we have carried out the 1H NMR spectroscopy of the compound and

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• ) [16][17], which allowed the assignment of the absolute configuration of 2 as (2R,3R,7R) (Figure 3). Moreover, the predicted ECD curves of 2 and its relevant enantiomer were computed at the [B3LYP/6-31 G(2d,p)] level, and the experimental ECD curve of 2 agreed well with the predicted one (Figure 4), in

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• material must be racemic. A catalyst must be involved in the reaction process and induce the asymmetry in the product. The product must be isolated in enantioenriched form. Each antipode of the racemic starting material must lead to the same major enantiomer of product. Type I: Stereomutative

• one enantiomer to product (Figure 2). Additionally, the rate of starting material racemization must be significantly faster than the rate of kinetic resolution in order to achieve maximum yield and selectivity. Perhaps the most well-developed class of type I enantioconvergent catalysis is dynamic

• . Deuterium labeling experiments have shown that the hydrogenation reaction occurs only on the chiral keto tautomer, and therefore the catalyst selects one enantiomer of the substrate when the reduction takes place. Enantioconvergent methods are not limited to carbon stereocenters. An exceptional example of

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• NOE correlation between H-2 and 3-OMe led to recognition that these protons adopt cis orientation. In order to elucidate the absolute configuration of 1, solution TDDFT-ECD protocol [14][15] was carried out on the arbitrarily chosen (2R,3R) enantiomer. The preliminary conformational search at MMFF

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• of 25 with retention of configuration (Scheme 2). The change from S to R is caused by a change in the CIP priorities of the substituents. Thus the faster running smaller peak in Figure 3A must correspond to the S,S enantiomer of 25. Assuming independent first order rate laws for the opening of the S

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• an interesting aspect is the observation that the two enantiomers of chiral terpenes can have very different smells, e.g., the (+)-enantiomer of carvone smells like caraway, while (−)-carvone occurs in spearmint and has a clear spearmint odor [2]. Odoriferous terpenes from bacteria were identified

• between the isopropyl group and H-6. The optical rotary power of [α]D22 = −44.9 (c 0.15, CH2Cl2) proved that (1R,6S,7S)-(−)-1 from S. viridochromogenes is the opposite enantiomer as in vetiver oil ([α]D = +120) [38], while it is identical to the compound obtained by acid-catalysed rearrangement of (+)-α

• -ylangene [39]. The (−)-enantiomer of 1 has not been isolated as a natural product before. Type I terpene cyclases exhibit a few highly conserved motifs that are directly involved in binding of the Mg2+ cofactor to which in turn the substrate’s diphosphate portion is bound [10]. This includes the aspartate

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• stereocontrol, while Tyr157 and Lys161 participate in pre-orienting NADPH for transfer of its pro-S proton [27][32]. The resulting secondary alcohol 43 is processed similar to its enantiomer 39 in actinorhodin biosynthesis to give (R)-DNPA (46) and finally graniticin (36) after tailoring. It has been proposed

• achiral intermediate is the precursor for two enantiospecific pathways [55]. After stereoselective reduction to the (6S,8S) or the (6R,8R, 71a) enantiomer of (E)-6,8-dihydroxy-2-methylnon-2-enoyl-CoA, respectively, the nonactate synthase NonS catalyses stereospecific oxa-Michael addition [56][57]. This

Stereodynamic tetrahydrobiisoindole “NU-BIPHEP(O)”s: functionalization, rotational barriers and non-covalent interactions

• Golo Storch,
• Sebastian Pallmann,
• Frank Rominger and
• Oliver Trapp

Beilstein J. Org. Chem. 2016, 12, 1453–1458, doi:10.3762/bjoc.12.141

• ][6], palladium [7][8], platinum [9][10] and gold [11][12][13] in combination with chiral co-ligands or counter ions that are used after alignment of the ligand’s axial chirality. One major advantage of stereodynamic ligands is that there is no need for separate preparation of one ligand enantiomer as

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• (−)-anverene (1, see below), the absolute configuration of which was determined by the isolation chemists on natural material by X-ray crystallography [10]. Interestingly, using the same enantiomer of ligand, the bromochlorides derived from prenol and homoprenol (5) have the same absolute configuration. This

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• turnover in the sense of induction based upon the ester substituent. The less bulky methyl and benzyl esters gave the (S)-enantiomer while the tert-butyl ester gave the (R)-enantiomer. The incorporation of aryl groups was not compatible with this reaction manifold, prompting Sibi to explore aromatic

• the major enantiomer was not defined (Scheme 3) [18]. Indium was used to initiate the addition of a perfluorobutyl radical to α-aminoacrylate 11 followed by hydrogen atom transfer to the resulting α-amino α-ester radical from (R,R)-12. Enantioenriched tryptophan derivatives are useful building blocks

• . Acylation of the hydroxy group of quinidine resulted in complete loss of enantioselectivity, suggesting that hydrogen-bonding contacts between the catalyst’s hydroxy group and the substrate are important for organizing the transition state. Using catalytic quinine (25) the pseudo-enantiomer of the quinidine

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• determining enantioselectivity? To answer these questions, we synthesized a 1,6-enyne containing an enantioenriched propargyl alcohol using our group’s zinc ProPhenol chemistry (Scheme 7). By employing the opposite enantiomers of the ProPhenol catalyst, either enantiomer of propargyl alcohol can be accessed

• , creating a larger energy difference between syn-(R) and anti-(R). This larger energy difference is reflected in the higher enantioselectivities obtained for the (R) enantiomer in THF (Table 8, entry 5). The smaller energetic difference between syn-(S) and anti-(S) means that there is less of a preference

• faster than the [2 + 2] cycloaddition, creating a classic Curtin–Hammitt scenario wherein all of the substrate is funneled into the observed enantiomer of product (Scheme 8). Rate k1 is much slower than k2 due to the severe steric hindrance imposed by the ligated chiral sulfoxide, which block alkene

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• stereochemical configuration of the quaternary carbon was established by a diastereoselective Michael addition between a chiral, single enantiomer, cyclic β-amido ester and a nitroolefin, and, in the case of nakadomarin A the reaction could be rendered catalytic using a bifunctional cinchonine-derived urea

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• has been reported to be able to inhibit the EWS-FLI1/RHA interactions specifically, significantly more potent than its (R)-enantiomer and racemic compound [12]. Additionally, the 3-hydroxyoxindoles as versatile intermediates have also been used to construct small-molecule libraries for drug screening

• amine of the catalyst and ketone substrate and protonation of the tertiary amino group. The protonated amine then served as hydrogen bond donor to activate the carbonyl group of isatin substrates, thereby facilitating the aldol addition. Interestingly, the authors obtained the R-/S-enantiomer by using

• the corresponding R-/S-organocatalyst, respectively. The stereoselectivity could be explained by the transition state proposed. The R-enamine formed from the corresponding R-catalyst and 1,1-dimethoxyacetone attacked the isatin substrate from the Re face, thus affording the R-enantiomer. In 2014, the