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

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• promote the formation of a specific enantiomer. The search for the best balance of these properties of the carbenoid intermediates was also sought through the use of different metals such as copper [3], rhodium [4], iron [5], ruthenium [6], iridium [7], osmium [8], and others. From these, copper and

• carboxylate complexes in their homochiral form (Table 1) [39]. Modest enantiomeric excesses were provided by the three tested catalysts. The reactions carried out with complex 17a and 17b show very similar stereoselectivity, forming the R-enantiomer of compound 16 as the main product after decarboxylation

• reaction. The catalyst 17c showed opposite enantioselectivity when compared to the catalysts 17a and 17b, with the S-enantiomer formed as the major product. In 1991, Doyle and coworkers published asymmetric synthesis of lactones from alkyl diazoacetates in high enantioselectivity by intramolecular rhodium

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• less active, affording a comparable level of diastereoselectivity than compound VII, but a lower ee value for major diastereoisomer 7a was measured (Table 1, entry 14). Moreover, the opposite enantiomer of product 7a was preferentially obtained, thus suggesting that the nature of the alkyl group on the

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• indole derivatives 2. Indeed, as discussed below, other authors proposed the compound 6 as a plausible bifunctional catalyst. The Enders’ group used its enantiomer (ent-6) to develop a pioneering scalable one-pot multicatalytic method for the C2/C3-annulation of the indoles 2 (Scheme 4) [26]. In this

• activate the 1,3-dicarbonyl compound 36 (Scheme 15). We would like to remark that although the authors indicated that the S enantiomer is obtained in their final products, they depicted the R configuration, as is drawn in the Scheme 15. Aza-Henry reaction Ellman’s group designed a set of pioneering (thio

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• demonstrated by Deng and co-workers [32][33][34]. In this excellent study, catalysts substituted with benzyl at the 9-OH position gave the best results (CPD-30, Scheme 8). This report also demonstrated that the enantiomer of β-nitroester 31 could be obtained using the corresponding pseudoenantiomeric

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• , followed by an evaluation of their enthalpic penalties or rewards and the mechanical strengths of the relevant hydrogen bonds (relaxed force constants; compliance constants). The protocol was able to reproduce the experimentally known enantioselectivity favoring the S-enantiomer. In a second step, the

• portion displayed in blue [15]. While only the S-enantiomer seems to be potent, linezolid shows activity against a wide range of Gram-positive bacteria such as vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae

• enantioselectivity (it is well known that (S)-linezolid is the only active enantiomer) of the recognition process [16][42]. Again, the working-shell was used for this purpose as starting structure. The chirality of linezolid was inverted in place inside the receptor. (R)-Linezolid was rotated by 180° around an

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• mainly occurs in the nucleophilic attack rather than in the complex formation. Nevertheless, the optical rotations attributed to each enantiomer of sarin are in contradiction to those described by Benschop and De Jong in 1988 [20]. Indeed, they determined that the (R)-sarin is dextrorotatory whereas the

• )-(−)-enantiomer would be hydrolyzed faster in presence of α-CD. They also studied the alkaline hydrolysis of the two enantiomers of isopropyl para-nitrophenyl methylphosphonate [65] and of isopropyl (S)-2-dimethylaminoethyl methylphosphonothioate [67] in the presence of α-CD at 25 °C. The result indicates that

• to better interactions between the included (−)-enantiomer and the secondary hydroxy groups responsible of the nucleophilic attack. In the 80s, Désiré and Saint-André studied the effect of the three native cyclodextrins on the hydrolysis reaction of tabun, VX, sarin and soman [68][69][70]. It appears

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• chiral ligands in palladium-catalyzed allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate. The D-fructo-PyOx ligand provided mainly the (R)-enantiomer while the D-psico-configurated ligand gave the (S)-enantiomer with a lower enantiomeric excess. Keywords: asymmetric catalysis

• ]. Thus, a positive optical rotation value refers to the (R)-enantiomer, whereas a negative value belongs to the (S)-enantiomer. In addition, the absolute configuration was independently determined by 1H NMR in the presence of the optically active NMR shift reagent (+)-Eu(hfc)3 [29]. All synthesized

• could be obtained. To our delight, however, ligand 10a was active in 1,2-dichloroethane at 50 °C and gave the opposite enantiomer (S)-14 with an enantiomeric excess of 59% (Table 1, entry 10). Similar to ligand 9b, the β-configurated D-psico-ligand 10b leads to a somewhat lower enantiomeric excess of (S

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• observed fluorescence output to concentration for each enantiomer. Comparison of our calculated versus actual % L-Tym for these measurements revealed a high level of both accuracy and precision, and we were also able to demonstrate the use of our sensors to accurately monitor yield and enantiopurity in

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• . The optical rotation value of compound 1 was consistent with that previously reported [15], which confirmed that the S-enantiomer of dapoxetine hydrochloride was synthesized successfully by using this route. Conclusion In summary, a novel and stereoselective synthesis of dapoxetine hydrochloride

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• strategy for the synthesis of diversely functionalized trihydroxypiperidines through double reductive amination of the D-mannose-derived aldehyde 2 (Scheme 1) [24][25]. Among the 1-azasugars accessed with this methodology, our attention was drawn to the enantiomer of natural 3,4,5-trihydroxypiperidine (1

• amination on aldehyde 2 allowed the synthesis of trihydroxypiperidines, among which the enantiomer of natural compound 1 and the N-alkylated piperidine 3. Synthesis of key azide intermediate 4 through the double reductive amination strategy from “masked” dialdehyde intermediate 2. Tetravalent and nonavalent

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• mmol) and ee 78%. The enantiomers were separated by HPCL using the following conditions: Chiralcel AD-H, n-hexane/iPrOH 70:30, 1.0 mL/min, 10 °C, 12.3 min (minor; R-enantiomer), 25.5 min (major; S-enantiomer). The product was dissolved in a mixture of dichloromethane (6 mL) and heptanes (4 mL) and

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• arises as a key methodology for chemical production of enantiomerically enriched chiral compounds in terms of atom economy and reduced waste generation [2][3][4][5][6]. Nowadays, many very effective methodologies exist that allow the formation of a chiral compound as a single enantiomer. However, and

• achieved by selecting the correct enantiomer of the catalyst, the relative configuration is typically governed by intrinsic factors associated to the mechanistic profile of the reaction and very often the formation of the major diastereoisomer is determined from the very beginning of the reaction and

• syn-3a in excellent yield, an acceptable 88:12 dr and 98% ee. As expected, the use of the pseudoenantiomeric catalyst 5 provided the corresponding enantiomer ent-syn-3a with similar results. Moving to cyclohexanediamine-based catalyst 6 resulted in the same behaviour as observed in our previous report

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• enantiomerically pure and configurationally stable nine-membered E,Z-dienone 80. The synthesis of the enantiomer of dienone 80, ent-80, was accomplished by a route parallel to that presented in Scheme 8a, starting from ent-77. The highly efficient construction of these versatile intermediates provides a basis to

• synthesize a variety of natural products containing this macrocyclic structural motif. Based on chiral enone 80 and its enantiomer, ent-80, coraxeniolide A (10) and β-caryophyllene (22) were synthesized in five and four further steps, respectively. The synthesis of 10 continued with a trityl perchlorate

• antheliolide A (18) by Corey. a) Synthesis of enantiomer 80, b) total syntheses of coraxeniolide A (10) and c) β-caryophyllene (22) by Corey. Total synthesis of blumiolide C (11) by Altmann. Synthesis of a xeniolide F precursor by Hiersemann. Synthesis of the xenibellol (15) and the umbellacetal (114) core by

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• alkylation (AAA) reactions [5][6][7] can be used in dynamic kinetic asymmetric transformations (DYKAT) [8][9][10][11][12][13][14][15] to provide single enantiomer products from racemic starting materials. Mechanistically some of these have been shown to occur by direct enantio-convergent transformations [16

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• Josiphos enantiomer used, in both cases with good enantioselectivities (85–92% ee). Subsequent chain elongation followed by a 1,4-ACA reaction was described and enabled the enantioselective insertion of an additional methyl group. With trialkylaluminium reagents Only a few systems are known to perform

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• same article the authors showed that only the (L)-enantiomer of dimethyl malate afforded polymers. A racemate of malate esters gave only short polymers; showing nicely that efficient polymerization of diacids can only be achieved with carboxylic groups of similar reactivity. The poly(hexanediol-2

Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

• Sara J. Krivickas,
• Chiho Hashimoto,
• Junya Yoshida,
• Akira Ueda,
• Kazuyuki Takahashi,
• John D. Wallis and
• Hatsumi Mori

Beilstein J. Org. Chem. 2015, 11, 1561–1569, doi:10.3762/bjoc.11.172

• ,S)-2. The other enantiomer (R,R)-2 was synthesized in the same manner. The cyclic voltammetry measurement on racemic-1 indicated the first and second oxidation potentials (E11/2, E21/2) and their difference ΔE (= E21/2 − E11/2) to be 0.52, 0.83, and 0.31 V by utilizing glassy carbon as working

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• : chiral diamines; enantioselective reduction; epinastine; mianserin; ruthenium complexes; Introduction Mianserin (1) is a tetracyclic compound widely used as a drug in the treatment of depression. Despite the fact that the (S)-(+)-enantiomer of mianserin is more potent than the (R)-antipode in

• pharmacological tests for antidepresant activity [1][2][3], it is still administered as a racemate probably due to the fact that no serious adverse effects have been recorded for the (R)-enantiomer. Interestingly, no enantioselective synthesis of mianserin has been developed so far. The synthesis of racemic

• another important active substance, epinastine, in enantiomerically pure form (Figure 1). Epinastine (2) is a histamine H1 receptor antagonist and is used as racemic mixture in eye drops to relieve the symptoms of allergic conjunctivitis. Analogously as in the case of mianserin, the (S)-enantiomer is the