Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• ][5][6][7]. The reaction involving a nitrogen-based nucleophile as the Michael donor is known as the aza-Michael reaction (aza-MR). In view of its ability to introduce a nitrogen-containing functionality at the β-position of an activated alkenyl- or alkynyl-substrate, over the years, it has developed

• catalytic systems, namely arylboronic acid alone, its dual combination with chiral thiourea and integrated catalyst having boronic acid functionality in the chiral thiourea molecule. The dual combination of arylboronic acid with chiral thiourea was found as effective as arylboronic acid alone for the

• intermolecular asymmetric Michael addition of alk-2-enoic acids 68 with O-benzylhydroxylamine (69) giving racemic mixture of the product in poor yield. However, the integrated catalyst having boronic acid functionality in the chiral thiourea molecule gave the desired β-benzyloxyamino acid as the single product

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• cryogels, degradation of the material is required, yet in many cases the cryogel is still required to perform some functionality during degradation. Therefore, it would be beneficial if the mechanical properties of the cryogel were measured throughout its degradation [25][29]. It has been suggested that

• ) functionality [97]. The cryogels were synthesised by photochemical crosslinking of N,N-dimethylacrylamide (DMA) and β-CD triacrylate (Figure 7) and aripiprazole was incorporated through inclusion inside the hydrophobic β-CD domains. The release of aripiprazole was monitored at pH 1.2 and 6.8, targeting oral

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• comprehensive combination of quantum mechanical calculations and experimental spectroscopic analysis of their NMR and ECD data, to have a unique tetrahydrofuran ring instead of the cyclopropane functionality. The absolute configuration of these five compounds were evaluated and all conserved as C6R, C1’S, C2’R

• the hydrogen source. Following protection of the alcohol moiety with PMBCl, ether 22 was realized in 93% yield. Afterwards, this species was transformed into the γ-keto α,β-unsaturated aldehyde 23 through an NBS-assisted furan oxidation procedure in moderate yield (65%). The keto functionality was

• desired epoxide 30 after one hour in 85% yield (dr 10:1). This species was next converted to the terminal carbonate derivative 31 to transform the epoxy functionality to a vicinal diol through a two-step manipulation involving protection of the terminal alcohol as Boc derivative followed by BF3·Et2O

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• heteroatom (hydroxy, amino) functionality (Scheme 2). Results and Discussion Our studies began (Scheme 3) by reaction of BuLi (4 equiv) with a mixture of stannane 4 [6] (2 equiv) and tetramethylpiperidine (TMP, 2 equiv), to generate methoxymethyllithium and LTMP, followed by addition of terminal epoxide 5

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• respective acid chlorides by using thionyl chlorides and these acid chlorides were then made to react with the -OH functionality of metronidazole to get different esters [7]. Here we report a convenient method for the synthesis of aliphatic and aromatic esters of metronidazole. Furthermore, derivatives of

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• employ the intriguing substrate 5. In comparison with 2-oxindole 4, compound 5 possesses ester functionality directly attached to the 2-oxindole ring – which would provide a functional handle at this position of considerably greater plasticity than anything previously evaluated in the literature. On the

• hydrogen bond-donating functionality – while keeping the N-3,5-di-tert-butylbenzyl unit unchanged – were then introduced. Removing the two electron-withdrawing -CF3 groups from the ureaphenyl moiety resulted in diminished enantioselectivity (Table 1, entry 5), whereas increasing the steric demand in this

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• the previous sections. For example, catalyst 25 bearing a nucleophilic aminoalcohol functionality interacts with the boronic acid reagent in the Reissert-type reaction with acylated quinolines (Scheme 5b) [36], while the phosphine moiety in the bifunctional phosphinothiourea catalyst 31 allows for

• excellent yields and enantioselectivities up to 95% and 98% ee, respectively. Cation–π interaction: expanding the functionality of hydrogen bond donor catalysts: The development of hydrogen bond donor anion-binding catalysts mainly focuses on the interaction and binding properties towards the anionic

• development of an enantioselective aza-Sakurai cyclization (Scheme 12) [70]. In this transformation, a chiral thiourea catalyst 58 with a dibenzothiophene functionality serves as a dual H-bond donor and Lewis base to facilitate the cyclization of hydroxylactams 56. Thus, indolizine and quinolidizine

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• by using [Pd(allyl)Cl]2 and JackiePhos as a ligand to obtain the polymer 30 in 52% yield. The deprotection of the N-Boc functionality led to the formation of poly[2,6-aminoazulene] 31 in excellent yields (Scheme 7C). The N-Boc-protected polymer 30 possessed good solubility in organic solvents and its

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• handles for derivatization and so represent important achievements for this method. In terms of additional functionality, we found that a thioether substrate could be engaged with reasonably good efficiency and enantioselectivity (Table 2, entry 11). On the other hand, while a nitrile was compatible with

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• observed for cellulose [67][79], while the multifluorinated compound formed considerably shorter platelets. Cellulose–xylan [80] and cellulose–chitin [81] hybrids were also obtained upon enzymatic polymerization of the respective dimers. An amino or azido functionality in the C-6 position allows for

• hydroxy group at C-3 and β-selectivity is easily achieved with the help of anchimeric assistance provided by a 2-O-acyl functionality. Despite these advantages, the synthesis of β(1–6)-Glc polysaccharides appears only in few reports [148][149], with short oligomers being prepared mainly to prove new

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• cation chelation via the N-2 atom electron lone pair and the C-3 substituent X=O functionality, respectively [24]. Tight ion pair formation with the sodium cation and both the N-2 atom and C-3 substituents of the indazole scaffold likely hinders the approach of the electrophile to N-2 and directs

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• attempt to introduce high yielding phosphoramidite building blocks suitable for automated ON synthesis, 2′-O-aminoethoxymethyl and 2′-O-aminopropoxymethyl nucleotides were developed. This method introduced the primary amine functionality through an azide reduction [73]. The corresponding monomers 37 and

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• install the free NH functionality. These findings highlight the convenience of manganese catalysis for the late-stage benzylic C–H amination of sophisticated bioactive molecules and natural products. The proposed mechanism of the Mn-catalyzed benzylic amination is shown in Figure 6. Initially

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• , where only the sesquiterpene trichodiene was detected with FPP, while other substrates were not accepted [69]. In contrast, bi-functionality was also observed for the pinene and guaiene synthase from Daldinia eschscholzii EC12 and the pinene and guaiene synthase from Hypoxylon sp. EC28 (Figure 3) [45

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• 17, followed by acetonide protection of the 1,3-diol functionality to yield the previously synthesized intermediate 4. The acetonide protecting group was chosen because of its stability under the future reaction conditions in addition to it being a convenient monitor of the relative configuration of

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• groups were challenged with WSSV by IM injection, with a dose of 10−6 Son2008 inoculum. (Herein “pellet feed” refers to when animals are fed with treatments, and “oral cavity” refers to when the VLPs treatment is given directly into the oral cavity through a needle to ensure intestinal functionality

• taken orally was more effective than when merely present in the feed as a coating. Taking the VLP-dsRNA28 orally assures capsid functionality by protecting the dsRNA structure. Administering VLP capsids inside the feed resulted in increased shrimp survival after challenged with the WSSV and treated per

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• were characterized via FTIR analysis to elucidate structural footprints of CM embedding and vTA photographing. The broad peak in the range from 3639 cm−1 to 3136 cm−1 corresponds to the hydrogen bonding between carboxyl and hydroxy groups with amide functionality of the hydrogel backbone. Significant

• release which is highly beneficial for agricultural delivery systems. The grand outcome of embedded g-CN-based surface photomodification has significant advantages in terms of its non-toxic process and cost-efficient material resources. Pore substructuring In porous materials, the functionality of the

• pores is responsible for the main catalytic activity, such as in carbonaceous materials [47][48]. When a network with full functionality cannot be formed easily, one can form a rigid neutral host and modify the pores subsequently. Herein, the nanoporous system is magnified to macropores in hydrogel

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• performance of these reaction types as a continuous-flow process is provided. Condensation reactions A carbonyl functionality is encountered in the vast majority of fragrance ingredients. The ability therefore to manipulate carbonyl moieties within a molecule will forever serve as an important transformation

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• their relative versatility in areas such as directionality, the tunability of the σ-hole, hydrophobicity, and donor atom size [14]. These traits allow for the design of novel supramolecular architectures which are directive and reproducible, without relying on the hydrogen-bonding functionality which in

• have been omitted due to the alternate functionality muting any effect the halogen would have on the porphyrin molecule. The bond lengths, angles, and atom displacements are outlined in Supporting Information File 2, Table S7. In the structure of compound 20, while containing a halogen, it is apparent

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• functionality. Thus, this synthetic route represents the first successful Cu-mediated coupling reaction of berberine substrates. The DNA-binding properties of the 10-O-arylberberine derivatives with duplex and quadruplex DNA were studied by thermal DNA denaturation experiments, spectrometric titrations as well

• strands [30]. Due to their straightforward synthetic accessibility by substitution at the 9-hydroxy functionality of berberrubine (1b), 9-O-substituted berberine derivatives are particularly attractive. But so far, only functionalization at this position by alkylation [23][24][25][26] and nucleophilic

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

• oligonucleotides challenging. Thio-LNA (Figure 7F), which has sulfur incorporated at the C2' position, has similar binding properties as amino-LNA and β-ᴅ-LNA, but with varying biodistribution patterns and a higher cellular uptake in mice [145]. Work looking at carba-LNA, which lacks the O2' functionality, has

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• report the efficacy, delivery capability, and functionality of the addition of peptides and RNA aptamers in facilitating entry through a simplified BBB model as well as to determine whether inclusion of these molecules could facilitate cell specific uptake. We further show that LNPs generally exhibit a

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• condensation between ketone and formylquinoline. The amine and the intermediate A undergo Michael addition furnishing the keto-amine B. Further, an intramolecular cyclization with the attack of the amino group onto the carbonyl functionality with subsequent elimination of a water molecule results in the

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• describe an extension of this method to gangliosides, and to the enzyme reactions associated with their biosynthesis. The formalism and the associated web application, now renamed Glycologue, provide a way to explore the effects of mutations that result in a loss of functionality, or promotion of disease