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

• presence sodium acetate in dioxane at 100 °C. The compound was prepared on the 10 mg scale in 67% yield. In contrast to its (3R,4R)-enantiomer (not shown), compound (3S,4S)-23 showed inhibitory activity toward human purine nucleoside phosphorylase (PNP) with a slow-onset binding constant Ki* = 0.032 nM. In

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• , produces species 9 and 12, respectively. It was proposed that the diastereomeric complex 12 has a higher propensity toward further hydropalladation than 9. Accordingly, the latter species releases the (S)-enantiomer of 2,5-dihydrofuran 3 (path I), while the former undergoes a series of reversible

• hydropalladations and β-hydride eliminations, resulting in the formation of a thermodynamically more favoured η2-complex 14, which ultimately produces the (R)-enantiomer of the isomeric product 4. Later, a number of research groups pursued the design of alternative diphosphine ligands to achieve better regio- and

• . Results and Discussion Our approach to the PHOX ligands with a chiral cyclopropyl backbone is presented in Scheme 3. The synthesis began from optically active 1-methyl-2,2-dibromocyclopropanecarboxylic acid (15) [65] readily available in both enantiomeric forms. The S-enantiomer of acid 15 was converted

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• precursor such as 13a (Table 1) [49]. A nucleophilic phosphide reagent was prepared by deprotonation of 13a in the presence of (−)-sparteine. The subsequent alkylation of the lithium phosphide with an electrophile proceeded with good enantiocontrol via dynamic resolution. One enantiomer is thermodynamically

• excesses were reported. As expected, a mechanistic study suggested that the major enantiomer of product was formed from the major diastereomer of the platinum–phosphido intermediate [63]. Glueck and co-workers also developed an analogous method for the tandem alkylation/arylation of primary phosphines on

• following years, the scope and mechanism were elaborated [202][203][204]. In accordance with the mechanism given in Scheme 10, it was concluded that the major enantiomer of the product 108 was derived from the major diastereomer of the Pd-phosphido intermediate. Korff and Helmchen have prepared several

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• use of isotopically labelled substrates in the sense of an isomer labelled guest method (ILGM) (Figure 3) which is closely related to the enantiomer labelled guest method (ELGM) introduced by Sawada [22]. Here, a competitive recognition experiment using a non-labelled substrate and a mass-labelled

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

• semiochemicals representing saturated polydeoxypropionates typically show syn-configuration, suggesting general principles in enzymatic chain elongation [16][18], we hypothesized (2E,4E,6S,8S,10S)-tetramethyltrideca-2,4-diene or its enantiomer to be the natural product. To establish a syn,syn-configuration of

• investigations. In analogy to the structure of A, compound B was assigned to be (2E,4E,6S,8S,10S)-4,6,8,10-tetramethyltrideca-2,4-dien-1-ol (23) or its enantiomer. According to the procedure described by Markiewicz et al. [23], racemic 23 was prepared by vinylogous Horner–Wadsworth–Emmons reaction of the

• -butyldimethylsilyl)]-β-cyclodextrin (50% in OV1701) as the stationary GC phase, operated at 100 °C. Under these conditions, the (2S,4S,6S)-enantiomer [30] is the later eluting stereoisomer, giving an α-value of (tr2:tr1) = 1.019 (see Supporting Information File 1, Figure S4). As a result of our investigations we

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -hydroxy-β-aminodecanoic acid (AHDA, 2a) and its enantiomer 2b. The enantiomer of 2a is the N-terminal part of the natural linear pentapeptide microginin, which is used as an antihypertensive agent. Keywords: AHDA; carbohydrate; chiron approach; enantioselective; natural products; non-proteinogenic amino

• enantiomer (2R,3S)-AHDA (2b). As a part of our continuous interest in the synthesis of chiral amino acids [22][23] and their utility in the synthesis of iminosugars [24][25][26][27][28][29], we report here an efficient and practical approach for the synthesis of both enantiomers of AHDA (2a and 2b) from the

• % yield as a white solid. The spectral and analytical data of 2a was found to be in good agreement with published data ([α]D25 +5.6 (c 0.51, 1 M HCl). [α]D22 +7.3 (c 0.37, 1 M HCl)) [18]. The synthesis of AHDA enantiomer 2b was accomplished starting from 3-O-benzyl-1,2-O-isopropylidene-α-D-ribo

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• the reaction, whereas an excess of NFSI led to poor asymmetric induction. In the former reaction, the major enantiomer of the recovered 5a was the S-form (Table 1, entries 2 and 3). This result also supports the proposed mechanism. To test the proposed reaction mechanism, we carried out the

• fluorination of enantioenriched 2a (61% ee, R favored) with 2 equiv of NFSI in the presence of each enantiomer of catalyst 1. As expected from the mechanism, good enantioselectivity was observed when (S)-1 was employed in the reaction, whereas the reaction proceeded more slowly to yield 4a with poor

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• observed, the spectrum calculated for the 5S,9S,10R-enantiomer showed a good fitting with a moderate ΔESI value of 58% [27]. To further corroborate the assignment of the absolute configuration of 1, ORD calculations were performed using the PBE0/cc-pVDZ//B97D/TZVP method. The ORD calculated for the 5S,9S

• ,10R-configuration in the non-resonant region matched with the one observed experimentally (Figure S10 in Supporting Information File 1). The good agreement of the experimental CD and ORD spectra with the ones calculated for the 5S,9S,10R-enantiomer revealed the absolute configuration of 1 to be as

• experimentally were done with SpecDis 1.61 [41]. Structure of decandrinin (1). Selected 1H–1H COSY and HMBC correlations for decandrinin (1). Diagnostic NOE interactions for decandrinin (1, B97D/TZVP-optimized structure): arbitrarily the 5R,9R,10S-enantiomer is shown. Determination of the absolute configuration

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• . Thus the S-enantiomer of 19 should be generated primarily. The experimentally favored enantiomer is indeed (S)-configured with 75% ee. The computationally found difference in energies is not high enough to wholly explain the experimentally found selectivity. This can be tentatively attributed to the

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• kinetic resolution [156], albeit with unsatisfactory enantiomeric excess. The undesired enantiomer was then selectively cleaved using another enzyme with reversed selectivity to give enantiopure pyranone 181. Cyclopropanation was achieved using a Michael addition initiated ring closure yielding diester

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

• , respectively. Treatment of each enantiomer of 7b with acetic anhydride and pyridine gave their acetate derivatives. Surprisingly, (+)-7b ([α]D +9.3) gave an acetate derivative with [α]D −8.7 and vice versa ([α]D –12 for (−)-7b and [α]D +13 for its acetate derivative). As anticipated, the 1H NMR spectrum (CDCl3

• enantiomers of 1 (shown in trace (a)), and that the (+)-enantiomer elutes before the (−)-enantiomer (traces (b) and (c)). Finally, the natural sample has the same retention time as the (−)-enantiomer (trace (d)). A co-injection experiment performed on a mixture of the synthetic (+)-enantiomer and the natural

• % isopropanol in n-hexane, flow rate of 10 mL min−1) with UV detection at 220 nm and a Chiralpak AD column (250 × 20 mm, Daicel Chemical Industries Ltd.) to give the (+)-enantiomer (2.7 mg); (−)-enantiomer (2.6 mg). The retention times were: 29.5 min ((+)-enantiomer); 32.1 min ((−)-enantiomer). (±)-(E)-1-(furan

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• )-Mosher ester [28][29]. Integration of the 1H MMR spectrum indicated the e.r. was 93.7:6.3 and Mosher analysis (See Supporting Information File 2 for details) confirmed the stereochemistry of the new asymmetric center of the major enantiomer as S in accord with the predicted outcome [25]. Silylation gave

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

• then furnished rac-4b, the substrate for enzymatic resolution. Using an immobilized lipase enzyme as the catalyst (and under slightly different conditions from those described in Scheme 1), one enantiomer of the racemic β-lactam 4b was completely transformed into the ester 5b, while the other

• enantiomer of β-lactam 4b remained intact. The net result was that a fluorinated stereocentre was rapidly constructed, with defined absolute configuration, within a nitrogen heterocycle. Conclusion When the concept of selective fluorination is applied in the context of N-heterocycles, the resulting molecules

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

• using the improved Sharpless conditions with the newer AQN based ligands, producing excellent ee’s for both enantiomers of the diol, 95% for the enantiomer derived from AD-mix α, and 97% for the enantiomer from AD-mix β (Table 1). The corresponding isolated yields under these conditions were 54% and 56

• obtained from integration of the signals for each enantiomer matched the chiral HPLC analysis of the derivatised dibenzoates closely; for example the ee’s for 28b and 28a, from the 1 mol % osmium, 5 mol % PHAL conditions, were 82% and 91% by NMR respectively and 83% and 91% by HPLC for the corresponding

• standard acquisition parameters revealing the partial enantiomer overlap. Partial 19F{1H} NMR (400 MHz, L-(+)-DIPT/CDCl3, 300 K) spectra of 28b and 28a using optimised conditions: SW 40; AQ = 0.8; O1P −230; d1 = 5; 32 or 64 scans. Key steps from the synthesis of 6-fluoro-D-olivose (6) from D-glucose (1

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• . As an example, (R)-limonene smells of oranges, whereas the (S)-enantiomer has a turpentine-like (with a lemon note) odor. The difference in physiological effects of enantiomers is of utmost importance especially for the pharmaceutical industry, but increasingly also in agrochemicals [2][3] and even

• in materials sciences, as evidenced by the introduction of chiral organic light emitting diodes [4][5]. In certain cases, one enantiomer may be harmful. This was the case, for example, with the drug thalidomide (Figure 1), the (R)-enantiomer of which was sold to pregnant women as a sedative and

• antiemetic in the 1960s. The (S)-enantiomer turned out to be teratogenic. The crucial role of chirality presents a great challenge for synthetic chemists. Asymmetric synthetic methods have emerged and after the development of ample analytical methods over the last few decades, asymmetric synthesis has seen

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

• 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

• natural product (Scheme 2). A subsequent 5-endo-cyclization of the resulting allenyl alcohols leads to a mixture of diastereomeric dihydrofurans, which can be separated by HPLC (only the (S)-enantiomer is depicted). This allows the synthesis of the natural product and its enantiomer by functionalization

• of both diastereomers. The cis-configured amino alcohol moiety at C-3 and C-4 is installed by azidation and subsequent reduction steps leading to the final products. The presented strategy allows the preparation of jaspine B, its enantiomer and two diastereomers, all of which are known for their

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• ][4][5][6] and its enantiomer ent-1 [7] have emerged as highly valuable starting points for target molecule syntheses which rely on dual olefin metathesis reactions. The two metathesis transformations may either be two identical CM [8][9] or RCM steps [10], yielding C2-symmetric products in which the

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• and D-glyceraldehyde (Scheme 5) [48]. Fortunately, the resulting diastereomers were easily separated with cation exchange resin (Ca2+ form) under elevated temperature to realize the preparative-scale production of both sugars [48][49][50][51]. L-Tagatose Unlike its enantiomer D-tagatose which is a

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• is TS11exo (Figure 7), is in good agreement with the experimental results in which a high ee of the corresponding stereoisomer was observed. The formation of the enantiomer (TS11ent) was found to have an activation barrier of 4.5 kcal mol−1 higher in energy. That difference can be a consequence of

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• continues even today with clevidipine (2.3, Cleviprex) which obtained FDA approval in 2008. In contrast to the previous compounds clevidipine is a very short acting calcium channel blocker and is used as a single enantiomer being administered intravenously rather than orally. Due to its labile

• demonstrated allowing biological evaluation of either enantiomer and comparison of the obtained results. Through these studies it was found that the S-(−)-enantiomer of amlodipine is the biologically active one although there appears to be no significant difference in the pharmacokinetic behaviour between the

• ). The required (R)-enantiomer of ethyl nipecotate can in turn be obtained by a number of different methods including the resolution of the racemate using L-(+)-tartaric acid obtained from full saturation of ethyl nicotinate. More modern methods involve a two-step process wherein ethyl nicotinate (2.52

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• in 11-R3 by the adjacent oxygen and hyperconjugation lead to a rather low BDH of 74.9 kcal/mol (B3LYP/6-31+G**). Biocatalytic allylic oxidation of theaspirane (1) with lyophilisates of PSA. Only one enantiomer of racemic compounds is shown. Intramolecular silyl modified Sakurai reaction to

• (1). Only one enantiomer of racemic compounds is shown. Oxidation of vitispirane (23) with PSA gave enone 24 and two diastereomeric allyl alcohols 26a and 26b. A putative intermediate is epoxide 25, which upon hydrolysis would give allyl alcohols 26a and 26b. Oxidation of the latter might provide

• enone 24. Only one enantiomer of racemic compounds is shown. Model substrates 11A and 11B that allowed a determination of accurate BDH298 values with the CBS-QB3 method. Optimized geometries and BDH298 values of radicals derived from 11 and 12 for gas phase and PCM calculations. Supporting Information

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• enantiomer. With eleven synthetic operations and a longest linear sequence of only seven steps, this route is highly convergent and employs a novel Rh-carbenoid-mediated formation of 30 as its key step. The synthesis of the natural enantiomer of (+)-K252a [(+)-27] was carried out in an analogous fashion

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• synthesis of the unnatural enantiomer of 1 enabled a structural revision of this compound and established its relative and absolute configuration as depicted in Figure 1 [4]. During the total synthesis of (−)-9-deoxyenglerin A, compound 1 had already been prepared enantiomerically pure in 14 steps starting

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition

• Yongguang Wang,
• Ruiyang Bao,
• Shengdian Huang and
• Yefeng Tang

Beilstein J. Org. Chem. 2013, 9, 1601–1606, doi:10.3762/bjoc.9.182

• that the two enantiomers of katsumadain A might show different behaviors in the biological studies from each other as well as from the racemic compounds, we also synthesized (+)-katsumadain A in a similar way by simply replacing the catatalyst B with its enantiomer in the organocatalytic 1,4-conjugate

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• R-enantiomer of (R)-3 and related aminoalcohols display both significantly higher potency and target selectivity than their S-enantiomers, we believe that this is a critical shortcoming in the previously reported syntheses [13][14]. Herein, we wish to report a detailed, reproducible and scalable