Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• substrate in aqueous media [25]. However, (R)-2 was obtained in 70% isolated yield and >99% ee. Finally, the product was converted into the corresponding dihydrochloride and compared with an authentic commercial sample in order to confirm the enantiomeric excess and absolute configuration. Conclusion

• racemic compound was used as reference. The absolute configuration was assigned by comparison of elution order of an authentic standard. General procedure for the transamination reaction with immobilized enzymes In a similar manner as previously described in [14], to 5 mL of a triethanolamine buffer (100

• boiling point byproduct acetone [2][3][4][5][6]. Since (R)- and (S)-selective TAs are available on the market, both enantiomers of the amine product are accessible. This point is particularly relevant since in most cases the pharmacological activity of a chiral drug is closely related to its absolute

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• 7 and 8 (Scheme 2) that proved to be identical with the natural products. The absolute configuration of the amino acid could not be determined due to the low amount of material present. Nevertheless, because NAMEs showed the common -configuration [23], this configuration also seems likely for the

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• depending on the absolute configuration of the chiral auxiliary used. The aldehyde 5 was first prepared according to a described procedure in two steps from methyl L-lactate (Scheme 1) [31]. The reaction with (R)- or (S)-oxazolidinones 6 led to the formation of 2,3-syn aldol products 7 in good yields with a

Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes

• Yo Hiranoi and
• Koji Nakano

Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255

• effect of linking two cobalt–salen complexes on the catalytic activity. The heterochiral complex (R,R,S,S)-1 demonstrated a much lower TOF of 237 h−1 than the homochiral one (R,R,R,R)-1 (Table 1, entry 6). Thereby, a combination of the same absolute configuration of two salen moieties was found to be

• favorable for a high catalytic activity. Such dependence of the catalytic activity on the absolute configuration contrasts with our previous observation in the epoxide/CO2 copolymerization where the heterochiral (R,R,S,S)-1 showed a much higher catalytic activity than the corresponding homochiral complex (R

• demonstrating dependence of the catalytic activity on the absolute configuration (Table 1, entries 10 and 12). However, the TOFs unexpectedly are much lower than those obtained by using (R,R,R,R)-1 and (R,R,S,S)-1. This trend was also observed for mononuclear complexes: the mononuclear complex rac-4 with fluoro

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

•  3) [32]. After derivatization and determination through Mosher’s ester analysis [33][34][35], the absolute configuration of the newly generated secondary hydroxy group-bearing carbon center (C6) was determined as R configuration (see Supporting Information File 1). The NMR analysis of the Mosher’s

• furnishing the chiral propargylic alcohol 25a with 92% ee (Scheme 5). After securing the absolute configuration at C6 in compound 25a by employing the Mosher’s ester analysis indicating S-configuration (see Supporting Information File 1), compound 25a was subjected to TBDPS protection followed by TBS

• propargyl alcohol involving 13 linear steps, respectively. Investigations towards exploring the current strategy for accessing other natural products and their analogues are currently underway. Proposed structures of a selection of diacetylenic polyol natural products. Absolute configuration analysis of

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• absolute configuration of carbamate 20 was confirmed by single-crystal X-ray analysis (Figure 2) [36]. Basic hydrolysis of carbamate 20 with 10% NaOH in refluxing EtOH provided aminoalcohol 21 which was subsequently N-benzylated with the corresponding benzyl bromides to yield pyrrolidines 22. Final

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• ). Furthermore, the absolute configuration of 88 was assigned by its single crystal X-ray analysis. 3.3. Application of spirolactams in natural product synthesis In 2001, Ciufolini and co-workers [103] employed PIDA (15) as an electrophile during the synthesis of naturally occurring tricyclic azaspirane

• overall synthesis. The absolute configuration of the synthesised compound was determined by comparing the optical rotary values with that of natural compound (−)-aculeatin (146a) and (+)-aculeatin (146b). In the continuation to previous work, the same research group [136] reported the synthesis of

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• methyl trifluoropyruvate (1b) instead of 1a resulted in a lower enantioselectivity (Table 1, entry 17). The absolute configuration of 2b was determined to be S by comparison with the optical rotation of reported data [32]. The absolute configurations of other alcohol products 2a and 2c–k were tentatively

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• actually 30-epiapratoxin E, thus correcting the originally proposed absolute configuration. Both diastereomers were tested for their antiproliferative activities in HCT116 cells, showing that natural (30R)-apratoxin E exhibited a higher activity than its (30S)-epimer. Due to their lower basicity, samarium

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• compounds a synthesis of references was required. For one of the main compounds, 5-hydroxy-4,6-dimethyloctan-3-one, the relative and absolute configuration was determined by synthesis of all eight stereoisomers and gas chromatographic analysis using a homochiral stationary phase. Another identified new

• Pogostemon cablin (patchouli) [30], but is also known from fungal sources [31][32]. We show here the corrected structure as reported by Amand et al. [31], while for the compound from patchouli oil the opposite absolute configuration has been assigned [33]. The absolute configuration of 16 from Daldinia

• 11 were separable by GC on a homochiral stationary phase, one of which matched the natural product in terms of same retention times and mass spectra (Figure 3). To clarify the relative and absolute configuration of the natural stereoisomer of 11 an enantioselective synthesis was performed (Scheme 5

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• spectrum, where molecular vibrational transitions occur (between 4000 and 750 cm−1) [3][36]. Recently, VCD has developed as a reliable spectroscopic method for the determination of the absolute configuration and conformational distribution of chiral molecules in solution [1][4][36]. The main drawback of

• richer in bands than a typical ECD spectrum (just like IR spectra vs UV–vis spectra) [1][4][36]. Nowadays, density functional theory (DFT) allows a calculation of the VCD spectrum of a chiral molecule, which then can be compared with the measured VCD spectrum and by this the absolute configuration (AC

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• absolute configuration assumed by the protonated N atom and the conformation of the arene–CH2–proline double free-rotating system, determine in turn the relative position of the negatively charged and bulky carboxylate group with respect to the macrocycle cavity (i.e., inwards or outwards). This provides a

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• (BM, solution and solid support) to the production of the VVIA peptide sequence, protected or not, depending on the strategy (all amino acids bearing L absolute configuration, Figure 1). The sequence has been chosen as it corresponds to the Aβ (39–42) tetrapeptide, a promising small therapeutic

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• previously reported to have germacrene A synthase activity during heterologous expression in Escherichia coli, was identified by extensive NMR-spectroscopic methods as 18-hydroxydolabella-3,7-diene. The absolute configuration of this diterpene alcohol and the stereochemical course of the terpene synthase

• conversion of stereoselectively deuterated terpene precursors, because the problem of determining the absolute configuration of the terpene under investigation is simplified to a problem of delineating the relative orientation of its stereocentres to the known absolute configuration at the deuterated carbon

• [12][13]. This approach was used to determine the absolute configuration of 3 using both enantiomers of (R)- and (S)-(1-13C,1-2H)GGPP [14], (R)- and (S)-(1-13C,1-2H)FPP, and (R)- and (S)-(1-13C,1-2H)GPP [12] in which the additional 13C labels were introduced to increase sensitivity in the HSQC

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• -workers demonstrated the potential of asymmetric cation-based phase-transfer catalysis to control the absolute configuration of the newly-installed stereogenic centre in this rearrangement reaction [141]. By using their spiro-quaternary ammonium salt catalyst B5 they were able to control the Neber

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• ); however, the best results continued to be obtained by using the conditions indicated in Table 1, entry 3. To establish the absolute configuration of product 2a, a sample was crystallized to give a suitable single-crystal for X-ray diffraction analysis. The resulting structure showed the R configuration

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• conditions provided (5’S)-17 and (5’R)-17 [12] (Scheme 3). The differences between 1H NMR data of the related diastereomeric compounds (Figure 2 and Figure 3) provided a conclusive evidence to unequivocally attribute the absolute configuration at C-5’ of the synthesized compounds. Thus, for compounds 11–15

Bifunctional organocatalysts for the asymmetric synthesis of axially chiral benzamides

• Ryota Miyaji,
• Yuuki Wada,
• Akira Matsumoto,
• Keisuke Asano and
• Seijiro Matsubara

Beilstein J. Org. Chem. 2017, 13, 1518–1523, doi:10.3762/bjoc.13.151

• - and diisobutylamide groups resulted in much lower enantioselectivities (2b and 2c). Substrates bearing cyclohexyl groups or a piperidinyl moiety provided the corresponding products in high yields; however, the enantioselectivities were not as high as that of 2a. The absolute configuration of 2d was

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• the catalyst d. The absolute configuration of 3g was determined by X-ray analysis (see Supporting Information File 1, Figure S1). Conclusion We have developed a highly efficient and practical strategy for a single step construction of saturated spirocyclopentaneoxindoles containing four consecutive

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• Hα/H6, which were inconsistent with the small JH6/Hα value (4.3 Hz) and the absence of an NOE correlation between Hα/H5ax in the experimental spectra. Accordingly, the relative configuration of 1 was assigned to be 4R*,6R*,αS*. In order to determine the absolute configuration, the low-energy

• -dehydroanhydrocycloheximides, respectively. It is noted that a compound of unspecified absolute configuration was recently reported to possess the same planar structure as 3 [11]. Photoinduced interconversion between 2 and 3 When elucidating the structures of 2 and 3, we understood that the interconversion between 2 and 3 is

Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee

• Kalliopi Sofou,
• Demosthenis Isaakidis,
• Apostolos Spyros,
• Anita Büttner,
• Athanassios Giannis and
• Haralambos E. Katerinopoulos

Beilstein J. Org. Chem. 2017, 13, 952–959, doi:10.3762/bjoc.13.96

• tertiary and a secondary carbon, respectively. Concerning the absolute configuration of costic acid, we propose that it is the same as that reported by Bawdekar et al. [39] as indicated by a value of [α]D = + 24.03 (c 1.3, MeOH) ([α]D = + 23.42 (c 1.3, MeOH) [39]). Costic acid is a known natural product

• [40], Ferula communis L [41], Laggera pterodonta (DC.) Benth [42], Nectandra membranacea (Sw.) Griseb [43], and Stevia polyphylla DC [44]. It has also been isolated from another species of Dittrichia, namely, Dittrichia graveolens (L.) Greuter [45]. The first study on the structure and the absolute

• configuration of the compound is from a report on the isolation of the acidic fraction of costus root oil [39]. The plant extracts exhibit a spectrum of biological activities [46]. D. viscosa extracts exhibited abortifacient, anti-implantational and luteolytic effects on rats [47]. The acidic components of its

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• C-13 as in pavidolide A or three at C-2, C-6 and C-13 in methyl sarcoate). Both related molecules and compound 5 have only one stereogenic center, i.e., at C-1. The reported absolute configuration of pavidolide A ([α]D20 +124, c 0.25, CHCl3) at C-1 is R [30]. The specific rotation value of 5 is +3.5

• and does not allow indicating any configuration for C-1 in compound 5. Due to the instability of the substance and its rapid degradation, it was not possible to determine the absolute configuration unambiguously. Structural similarity of the compound 5 with pavidolide A and close relationship between

• and NOESY; all NMR spectral data in Supporting Information File 1, Figures S32–36 and Table S4) experiments and propose the absolute configuration of bisepoxide 12. Bisepoxide 12 has five stereogenic centers, found at the epoxide moieties between C-3 and C-4, and C-11 and C-12, as well as C-2 of the

Diastereoselective anodic hetero- and homo-coupling of menthol-, 8-methylmenthol- and 8-phenylmenthol-2-alkylmalonates

• Matthias C. Letzel,
• Hans J. Schäfer and
• Roland Fröhlich

Beilstein J. Org. Chem. 2017, 13, 33–42, doi:10.3762/bjoc.13.5

• in a statistical ratio of 1:2:1. Facial selectivity is indicated by deviation from this statistical ratio. The selectivity for re,re-coupling vs re,si-coupling is given by the ratio 2 (a:b), the selectivity for re,si- vs si,si-coupling by b:2c (Table 2). The absolute configuration of the major

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

• chain. As part of the ongoing EU-project “SPICE profiling”, MDMB-CHMCZCA samples from test purchases in online shops and police seizures were analyzed to obtain analytical data and chemical properties. Another aim was to assess the absolute configuration and optical purity of the selected product

• CO and/or a cyclohexyl radical or methylenecyclohexane. As MDMB-CHMCZCA bears a stereogenic center at C-1', the elucidation of the absolute configuration of the sample was attempted by ECD spectroscopy. While the UV spectra can be adequately predicted by TD-DFT calculations (time-dependent density

• functional theory, see Supporting Information File 1 for details), a comparison of the experimental and calculated ECD spectra did not allow for a safe assignment of the cannabimimetic’s absolute configuration (Figure 4). The main two positive ECD signals in the range above 230 nm are correctly predicted by