Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• phosphorothioate Rp-stereoisomer (Rp-PS, i.e., phosphate with one of the non-bridging oxygens replaced by sulfur) in bacterial genomes, where it may serve a protective role against nucleases [4] and its loss results in genomic instability [5]. There are over a hundred known base modifications in RNA and the Rp-PS

• '-stereoisomer of FANA, FRNA also demonstrates improved binding to RNA, relative to DNA [185]. Circular dichroism spectra of FANA/RNA and ANA/RNA duplexes show similarity to that of DNA/RNA [178][183]. Both ANA and FANA demonstrate good stability to nucleases [183][186]. Hybrid duplexes of ANA and FANA with

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• cyclic sulfate 9 in 95% yield. The cyclic sulfate moiety in 9 was reacted with sodium azide in DMF at 80 °C followed by acidic hydrolysis of the resulting acyclic sulfate ester to give azidotriol 10 as a single stereoisomer in 97% yield (Scheme 2). For further structural proof, the azidotriol 10 was

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and cis isomers of 2-hydroxy-2-oxo-3-[(phenoxyacetyl)amino]-1,2-oxaphosphorinane-6-carboxylic acid (16, Figure 3) were prepared and evaluated as inhibitors of the zinc-containing β-lactamase II from B. cereus. However, neither stereoisomer had any significant activity [6]. The phosphonodepsidipeptide

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• were obtained by the Michael addition of NaSMe to ethyl propiolate (45), yielding a mixture of stereoisomers inseparable by silica gel column chromatography (92%). The major stereoisomer was found to be (Z)-42 (dr 94:6), whose preferred formation may be a result of a chalcogen–chalcogen interaction

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• to proceed under the action of a catalytic amount of a base, and only 2 mol % of t-BuOK led to the formation of the desired adduct 3aa as a sole stereoisomer in 84% isolated yield under the same reaction conditions (Table 2, entries 6−8). The E-stereochemistry of 3aa was deduced from the NMR data of

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• acid, as previously reported [45]. In the next step, the electrophilic addition of iodine monochloride to the double bond of the enesulfonamide 10, followed by a nucleophilic attack of methanol on the formed iodonium ion afforded the α-methoxy-β-iodopiperidine 11 as a single stereoisomer (91% yield

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• conformers were calculated using time-dependent DFT (TDDFT) at the B3LYP/6-311+G(d,p) level of theory. The negative Cotton effect observed at 236 nm in the measured spectrum was in good agreement with that in the calculated ECD spectrum of the (7S,10R,11R)-stereoisomer (Figure 4A). Thus, the absolute

• configuration of muyocopronone A (1) was established as the (2′R,3′R,4′S,7S,10R,11R) stereoisomer. Muyocopronone B (2) was also obtained as yellow amorphous solid, and its ESIMS was consistent with the molecular formula C25H32O7, thereby suggesting the addition of two hydrogen atoms relative to 1. A comparison

• ). Furthermore, the calculated spectrum for the side chain-simplified model of the (7S,10R,11R)-stereoisomer was in good agreement with the experimental spectrum of 1 (Figure 4B and Figure S1, Supporting Information File 1). Therefore, the absolute configuration of 2 was also determined to be the (2′R,3′R,4′S,7S

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• assumed by analogy. Dehydration of compound 13b in the presence of p-toluenesulfonic acid gives dihydropyran 14 as a single stereoisomer (Scheme 4). Conclusion In summary, a convenient protocol for the synthesis of phosphoryl-substituted pyrrolidines with three contiguous stereocenters via asymmetric

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