Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• of the C-6 stereocenter (Scheme 13) [15][16]. The administration of the vinyllithium reagent, generated from the addition of the vinyl bromide 80 to 79, gave a separable 1:1 mixture of the diastereomeric alcohols 81a and 81b. The undesired stereoisomer 81b was converted into 81a by a Mitsunobu

• , followed by a transmetalation provided a vinylzinc reagent that was coupled with 48 to afford 128, for which only the E-stereoisomer was observed. Notably, the Negishi conditions were tolerant to the azide present in 48 and the oxirane and 1° iodoalkane present in 91. The subsequent reduction of the azide

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• -stereoisomer with the B(pin) substituent in the β-position was obtained exclusively. The PKR was compatible with aromatic groups containing substituents with differing electronic properties, heteroaryl groups, benzopinacol, 1,8-diaminonaphthalene, olefinic, and aliphatic groups. However, the PKR failed when

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• energy conformer of stereoisomer 23a and those of two minimal energy conformers of 23b (23b1 and 23b2) in DCM solution, based on DFT calculations. Rearrangement of methylenedioxy-substituted aminoaldehyde 1a to regioisomer 2a and formation of the dimer-like product 3a. Synthesis of 1-arylisoindoles 6 and

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• hydroxylamines using malonoyl peroxide, providing N-tosylated 3-aryl-substituted 4-hydroxyisoxazolidines in a highly stereoselective manner in favor of the C-3/4-trans isomers [27]. We believe that the 3-substituted isoxazolidin-4-ols, represented by the general structures of the trans and the cis stereoisomer 3

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• stereoisomer, despite the presence of two isomers in the starting materials 3. The 1H NMR and 13C NMR spectra clearly showed the chemical equivalence of the two ortho-palladated fragments, while 19F NMR spectra showed the equivalence of the bridging trifluoroacetate ligands. This means that only the transoid

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• stereoisomer 136 as the major product (Scheme 32). The reductive amination of 3-fluoro-3-phenylpyruvic acid (144) obtained by the fluorodehydroxylation of the enol form of ethyl 3-phenylpyruvate 142, using DAST instead of SF4 followed by hydrolysis, produced both threo and erythro-diastereomers of 136 [68

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• . Synthesis of artemisinin using TPP and supercritical CO2. Synthesis of artemisinin using chlorophyll a. Quercitol stereoisomer preparation. Photocatalyzed preparation of naphthoquinones. Continuous endoperoxidation of conjugated dienes and subsequent rearrangements leading to oxidized products. The Opatz

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• synthesis of the marine sesquiterpenoid (−)‐clavukerin A (9) and its stereoisomer (−)‐isoclavukerin A (10, Scheme 13). The sterically related analogs (+)-clavularin A and clavularin B have also been produced by this protocol. It is noteworthy, that the authors succeeded in preparing the two enantiopure

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• recrystallizations, the major isomer 11a could be isolated as a single stereoisomer. It proved impossible to isolate a sample of isomer 11b without a significant and dominant contamination with 11a. Thus, it was with some frustration that we were unable to prepare a suitable sample, both in quantity and purity, of

• isomer 11b for subsequent analysis. Stereoisomer 11a was a crystalline solid and a suitable crystal was subject to X-ray structure analysis and the structure is shown in Scheme 4. In this way the stereochemistry of 11a and 11b could be confirmed unambiguously. Evaluation of liquid crystal candidates 8

• . Notably for both the axial and equatorial conformers, the orientation of the CF2 group, and therefore its dipole, remains perpendicular to the long molecular axis (requirement for +ve dielectric). A similar result was obtained for stereoisomer 11b (see Supporting Information File 1) again with the first

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• 8.1 to 10.7 ppm and for the benzyl derivative 15 at 6.63 ppm. In the case of aldoxime carbamates three reactions gave mixtures of inseparable Z-stereoisomers ≈10% along with the major E-stereoisomer (products 25–27). It has been noted in the literature the preferable E-conformation for oxime

• , all aldoxime derivatives had the corresponding absorption of the oxime C–H in the area 8.3–8.8 ppm, and the three products giving the Z-stereoisomer showed the same proton upfield at ≈8.16 ppm. However, we wanted to further investigate which is the most stable stereoisomer. Thus, 1H chemical shifts of

• shifts with GIAO method in PBE0/6-311+G(2d,p) level of theory were in complete agreement with the experimentally found values, allowing us to verify the preferred stereoisomer of compounds 25–27 as E. Calculated 1H chemical shifts for C(H)=NO proton of the E- and Z-stereoisomer compared with the

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• -triazol-1-yl)cyclohexanes 12 and 14, having the same configuration as compounds 7f and 8f, respectively, were analyzed. Both compounds formed gels, but the trans stereoisomer 12 did so only at a low temperature (8 °C) in DMSO (G = 1.1, w/w), similar to the β-anomer 7f, which possessed the same trans

• configuration. On the other hand, the cis stereoisomer 14 formed an opaque gel at room temperature in DMSO/H2O, 9:1, v/v (G = 0.8, w/w), showing a higher potency for gelation, similar to 8f. As such, this relationship mirrors the behavior observed for the 7f/8f pair. Table 2 also contains the different Tgs

• thin and short fibers. The xerogel of compound 12 showed long, thin, and relatively straight fibers, with lack of torsion, as well as regularity of the network. Its cis stereoisomer 14 showed a fibrous network, but of much shorter length. However, the gel of compound 10 showed a different morphology

Multiple threading of a triple-calix[6]arene host

• Veronica Iuliano,
• Roberta Ciao,
• Emanuele Vignola,
• Carmen Talotta,
• Patrizia Iannece,
• Margherita De Rosa,
• Annunziata Soriente,
• Carmine Gaeta and
• Placido Neri

Beilstein J. Org. Chem. 2019, 15, 2092–2104, doi:10.3762/bjoc.15.207

• ) [31][32][33][34][35][36][37]. Our group previously reported [17][18] some examples of directional threading of calix[6]-wheels [38] in which the endo-alkyl stereoisomer in Figure 9 is preferentially formed over the endo-benzyl one [17][18]. On the basis of these empirical observations, we have

• indicated by the presence in the 1H NMR spectrum of shielded alkyl resonances at negative value of chemical shift between −0.73 to −0.82 ppm. No evidence of the (endo-benzyl)-8+6 pseudo[2]rotaxane stereoisomer was detected in the 1H NMR spectrum of the 1:1 mixture of 8+ and 6. An ESI-FT-ICR mass spectrum

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• respect to the orthogonal plane of the axle, only one stereoisomer of the [6]rotaxane was obtained. Keywords: cucurbit[6]uril; cyclodextrin; macrocycles; mechanostereoisomer; rotaxane; Introduction Cyclodextrins (CDs) are macrocycles composed of glucoses linked via α-1,4-glycosidic bonds. CDs of six (α

• orientation, possibly due to inter-ring interactions with the CB[6], to give the [6]rotaxane as one single stereoisomer. Considering the ability of γ-CD to form stable 1:2 inclusion complexes, these singly threaded [n]rotaxanes could serve as an entry point to other high order interlocked structures by

• could be four possible orientations of the three interlocked γ-CD to give four different triazole environments (Figure 3b). Yet, only one of the four (isomer I or II) possible isomers has been observed in the 1H NMR, suggesting that 6R was obtained as a single stereoisomer. In fact, cooperative binding

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• of cis-indolylvinyl isonitrile, but also on the C-2, which is supressed in the presence of Mg2+ ions. AmbP3 transfers the dimethylallyl group on C-2 of hapalindole U in the reverse manner, but on C-2 of its C-10 stereoisomer in the normal manner. This review highlights the molecular bases of the

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• triethylamine and were pleased to obtain good yields of the adducts 7a–c and 8a,b (Scheme 2). In each case, the products 7a–c and 8a,b were formed as a single regioisomer and stereoisomer. The selectivity in favour of the isomer drawn in Scheme 2 was verified by single crystal X-ray analysis of the adduct 7c

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• . Isolation of the product was then possible through repeated column chromatography. Similarly, the same group was also able to isolate the saddle stereoisomer of a chiral nonamethoxy-substituted CTV in which every arene unit carries three additional substituents through HPLC on a chiral stationary phase [27

• necessary to collect enough material to record sufficient 1H and 13C NMR spectra. The spectra were very similar to those published by Luz [26], thus verifying our assumption. Please note, that the saddle stereoisomer of a CTV undergoes very fast intramolecular pseudorotational motions to change between its

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• . The configuration of C-5 in each stereoisomer was established using NOESY experiments and theoretical models. The main limitation of this approach was the impossibility to incorporate both aromatic and sterically hindered amines (e.g., tert-butylamine). Besides the reports of Rivera’s and Ramírez’s

• components, keeping formaldehyde as oxo component to obtain a single stereoisomer. The library was also integrated by the Ugi-4CR products derived from the 6β-ecdystereoidal amine (also used as precursor of isocyanide 28), while all compounds were evaluated as antiproliferative agents against T-leukemia cell

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• . cIsolated yield of one of the diastereomers as pure stereoisomer after several recrystallization steps. ORTEP representation of compound (R*,S*)-4a with thermal ellipsoids at 50% probability. Opposite enantiomer is omitted for clarity. The atom numbering does not follow IUPAC nomenclature. Synthesis of

Synthesis of the aglycon of scorzodihydrostilbenes B and D

• Katja Weimann and
• Manfred Braun

Beilstein J. Org. Chem. 2019, 15, 610–616, doi:10.3762/bjoc.15.56

• exclusively, so that, after cleavage of the ester groups, epi-scorzodihydrostilbene D (13) was obtained as single stereoisomer (Scheme 4). Obviously, the conditions required in the glycosylation reaction – excess of the Lewis acid and elongated reaction time – resulted in the formation of the

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• (HPA-12, 1, Figure 1) as the first inhibitor of CERT-mediated ceramide transport [11]. However, the initially determined (1R,3R) configuration of the most active HPA-12 stereoisomer (compound 1, Figure 1) was later revised to (1R,3S) configuration (compound 2, Figure 1) by Berkeš et al. in 2011 [12

• . However, after the structural revision of the most active stereoisomer, Kobayashi et al. synthesized (1R,3S)-HPA-12 (2, Figure 1) using a Zn-catalyzed asymmetric Mannich-type reaction in water, and unambiguously ascertained the revised configuration by X-ray crystallography [14]. The other syntheses of

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• decomposition of this stereoisomer including racemization at Cα. From pentose via 2,3-aziridino-γ-lactone In the so called “2,3-aziridino-γ-lactone methodology” [18][99][100] ribose (or lyxose) is used as a starting material [101][102] which is transformed into the lactone 95 in several steps [99]. Boron

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• -closing metathesis of 24 now smoothly afforded 25 in high yield. Dihydroxylation selectively yielded the desired stereoisomer of diol 26, which was subsequently protected as isopropylidene acetal. In the next step, after removal of the TBS group and mesylation, attempted substitution with NaN3 resulted

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• catalysts, bicyclic lactone (±)-4 a stereoisomer of (±)-3 furnished olefinated γ-lactone (±)-6 similar to (±)-5 (Scheme 3, Table 2). Unfortunately, ROM reactions, however, took place with total conversions, they were always accompanied by the formation of a significant amount of polymeric materials (ROMP

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• H3B·P(n-C8H17)3 (1%), H3B·P((CH2)13CH2)(n-C8H17) (8%; see text for tie bars that indicate additional phosphorus–carbon linkages, which are coded in the abstract with italics), H3B·P((CH2)13CH2)((CH2)14)P((CH2)13CH2)·BH3 (6·2BH3, 10%), in,out-H3B·P((CH2)14)3P·BH3 (in,out-2·2BH3, 4%) and the stereoisomer

• upon independent syntheses from the dibridgehead diphosphines 2 obtained in Scheme 1 [6], they were assigned as in,out-2·2BH3 (4%) and the stereoisomer (in,in/out,out)-2·2BH3 (2%), as shown in Scheme 2. The depiction of the latter as an out,out (vs in,in) isomer in Scheme 2 is arbitrary, but represents

• rather tedious column chromatography: the dibridgehead diphosphine diborane in,out-2·2BH3, its constitutional isomer 6·2BH3, and its stereoisomer (in,in/out,out)-2·2BH3. It can be inferred from the top spectrum that the three products were the major components and moreover present in approximately equal

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• the enzyme. While the dominant form of nicotine found in tobacco is (S)-nicotine, the (R)-stereoisomer is also found at detectable levels [22]. Nicotine dehydrogenase is reported not to be stereospecific, in that it can catalyze the hydroxylation of (R)-nicotine to (R)-6-hydroxynicotine; thus, this