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

• -arylnitroolefins 101 and the best results (yield 99%, ee 91%) were obtained in the reaction of benzylamine (R1 = Ph) on using the NHC precursor as shown below in the presence of hexafluoroisopropanol (HFIP) as additive along with molecular sieves (4 Å) (Table 23) [63]. The role of HFIP is to act as proton shuttle

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• with greater than 80% ee. As a third example of an enantioselective α-ketol rearrangement, Dai et al. used a chiral Al(III) catalyst to induce the rearrangement of 3 (Ar = Ph) and several aryl derivatives 9 (Figure 4) [6]. Among the N,N′-dioxide ligands explored, 11, which was derived from ʟ

• episilvestrol (35), natural products with potent anticancer properties. The step prior to the rearrangement involved a photoinduced [3 + 2] cycloaddition between hydroxyflavone 36 and methyl cinnamate (37), resulting in the bicyclic α-ketol 38 as a mixture of diastereomers (Ph and CO2Me groups trans) (Figure 9

• later explored alternative Brønsted and Lewis acids that could effectively catalyze the rearrangement of symmetric α‑hydroxy aldimines [29]. A catalyst screen was performed on the model substrate 97a (97 with R = Ph; Figure 19a) using three different Brønsted acids (acetic acid, sulfuric acid, and p

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

• Stimuli-responsive properties are often desirable for biomaterials used in drug-delivery applications. Here, we focus on temperature and solution pH response of cryogels as detailed below. 3.1. Temperature-responsive cryogels This is a property which can easily be applied and manipulated through careful

• [11][33][39]. Thermoresponsive cryogels comprising oligoethylene glycol have also been reported with dual shape memory behaviour [40]. Natural polymers such as cellulose derivatives, chitosan, gelatin, and dextran exhibit temperature-responsive properties and have been used in cryogels. 3.2. pH

• -Responsive cryogels The degree of swelling is affected by the chemical composition of the cryogel, and the nature of the medium, such as pH, ionic strength, and swelling medium composition [34][41]. This affects the interactions of pH-sensitive polymers (both polymer–solvent and polymer–polymer interactions

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• described in this article. Results and Discussion The benzoyl-containing enaminone 15a (Ar = Ph) was selected as a model for investigating conditions for the cyclization. This compound was conveniently prepared by Eschenmoser sulfide contraction [29][30], as shown in Scheme 2. The route entailed initial

• N-phenacyl analogue 11 (Ar = Ar’ = Ph), the ester-containing enaminone 15a proved to be completely stable during chromatography on silica gel or upon dissolution in acetic acid at room temperature (conditions under which we had observed cyclization of vinylogous amides 11 [18]), and spontaneous

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• substituents, the reactions of the MBH carbonates with H or alkyl groups were also investigated. For the carbonate with R = H, the reaction worked pretty well to give the mono-allylic product 3j in 84% yield. However, when R = Ph(CH2)2- as an example, a longer reaction time was needed and the product 3k was

• , respectively). However, the reaction of 2,4-lutidine with 2a led to complex results with several indistinct by-products formed, and only 39% yield of the desired product 4a was isolated. The R2 group on the 2-alkylpyridines were then investigated. When R2 = Me or Ph, the reactions also proceeded well

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• ]carbazoles 4a–l in satisfactory yields. Indole itself and N-methylindole could also be successfully employed in the reaction. The N–Me, N–Ph, and N–Bn substitution in the maleimide moiety showed only a marginal effect on the reaction outcome. Various chalcones with electron-donating methyl and methoxy groups

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• Erlenmeyer flask containing 150 mL modified SGG medium (glycerol 10 g, corn steep powder 2.5 g, peptone 5 g, soluble starch 10 g, yeast extract 2 g, CaCO3 3 g, NaCl 1 g, in 1 L H2O, pH adjusted to 7.3) [45]. The flask was left shaking at 160 rpm in a closed system shaker for ten days at 28 °C. Subsequently

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

• protons of –N–CH2-CH2–Ph. A singlet peak at δ 1.86 is attributed to methyl protons on the imidazole ring. The 19F NMR spectrum of 1H-1,2,3-triazole compound 5c showed a singlet at δ −113.61 corresponding to one fluorine atom of the phenyl ring. The high-resolution mass spectrometric data at 317.1141 (M

• aromatic protons of the phenyl ring. A singlet signal at δ 7.95 is for the 1H-imidazole proton. Two doublet signals at δ 4.73 and δ 4.71 are assigned to the four methylene protons of –N–CH2-CH2–Ph. A singlet peak at δ 2.48 is due to the methyl protons on the imidazole ring. The high-resolution mass

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• washed with tap water, the cells were stained with 0.4% SRB solution and incubated for 30 min at room temperature. These cells were washed to remove the unbound dye and subsequently solubilized with 10 mM unbuffered Tris base solution (pH 10.5). The absorbance was measured spectrophotometrically at 520

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• ((4-carboxybutyl)triphenylphosphonium bromide), which was chosen as a target agent for the herein conducted studies, and covalently coupled to PPM-NP and MPM-NP particles. The reaction was conducted in aqueous medium, using 5 equiv excess of TPP-COOH to RAFT-end group. The pH was first adjusted to 5.2

• mmol, 5 equiv to RAFT end group) and N-hydroxysuccinimide (NHS) (0.025 mg, 0.00022 mmol, 5 equiv to RAFT end group) were added (stock solutions were made in Milli-Q water and 25 µL of stock solution were added accordingly). The pH was corrected to 5.2 using 0.1 M NaOH or 0.1 M HCl solution. The

• solution was stirred for 45 min and the pH was adjusted to 8.3 and the solution was stirred for 3 days at room temperature. The particles were purified by dialysis in Milli-Q water with frequent solvent change (regenerated cellulose membranes, MW cut-off 6000–8000 g mol−1) and analysed via DLS experiments

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• chromosome known as Philadelphia (Ph). Ph is the result of the reciprocal chromosomal conversion between the proto-oncogene Abl1 of chromosome 9 and the BCR gene on chromosome 22 [3][4]. Research activity on compounds able to act as protein tyrosine kinase inhibitors (TKIs), which has intensified since the

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• used in pH-sensitive fluorescent materials [10] and laser technologies [11][12][13][14]. Moreover, xanthenes are present in some natural sources, such as santalin pigments found in many varieties of plants [15][16]. There have been many studies on the synthesis of xanthene derivatives to date because

• synthesized by Grignard reaction of 1a–l and aryl(or alkyl)magnesium bromides. Then 3a–l were prepared by oxidation of 2a–l using PCC. The final alkene compounds 4a–l were obtained by Wittig reaction using Me(Ph)3PBr, t-BuOK, and NaH. All substrates were purified by crystallization or column chromatography

• , K2CO3, DMF, reflux, 2 h, 91%; (ii) PhMgBr, dry THF, 0 °C, 2 h, 86%; (iii) PCC, CH2Cl2, rt, 2 h, 80%; (iv) Me(Ph)3PBr, t-BuOK, NaH, dry THF, rt, 3 h, 85%. Plausible reaction mechanism for the cyclization reaction of alkene 4a. Screening of catalysts for intramolecular FCA of 1a.a Exploration of solvents

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• .) 0.2%, NaCl 0.2%, CaCO3 0.1%, and agar 1.5% in distilled water of pH 7.0) was inoculated into a 500 mL K-1 flask containing 100 mL of the V-22 seed medium (soluble starch 1%, glucose 0.5%, NZ-case 0.3%, yeast extract 0.2%, tryptone (Difco Laboratories) 0.5%, K2HPO4 0.1%, MgSO4·7H2O 0.05%, and CaCO3 0.3

• % in distilled water of pH 7.0). The flask was shaken on a rotary shaker (200 rpm) at 30 °C for 4 days. For the production of nomimicins B (1) and C (2), the seed culture (3 mL) was transferred into 20 500 mL K-1 flasks, each containing 100 mL of the A16 production medium (glucose 2%, Pharmamedia

• (Traders Protein) 1%, CaCO3 0.5%, and Diaion® HP-20 (Mitsubishi Chemical Corporation) 1% in distilled water of pH 7.0). The inoculated flasks were placed on a rotary shaker (200 rpm) at 30 °C for 7 days. For the production of nomimicin D (3), the seed culture (3 mL) was transferred into 20 500 mL K-1 flasks

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• ideal chemical components for the generation of smart devices. Depending on the polymer structure, including backbone and functional groups [10], their properties can be reversibly influenced by external chemical (e.g., pH value [11][12], ionic strength [13], polarity of solvent [14]), biological (e.g

• the underlying thermodynamic mixing theory. However, although the influence of certain molecular parameters such as chain length, concentration, pH or low molecular weight additives are discussed, the thermoresponsive behavior of polymers is exclusively considered as free polymer chains in solution

• observed by, e.g., zeta potential measurements. Two scaling regimes can be defined as limiting cases using the specific localization of the counterions that results from additionally added salt: the salted brush and osmotic brush [136][137][138]. These additional counterions, in addition to pH changes

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• incompatible with either base-sensitive or acid-sensitive substituents, as the desired SMAHOs are isolated after acidification to pH ≤ 2. It was thus impossible to prepare reagents bearing a phthalimide, an ester or an acetal group. This limitation is overcome by the other possibilities afforded by this

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• , 11 of them were never synthesized before. Markedly, noncharged structures, negatively charged cyanine bearing Na+ as counter cation, and positively charged cyanines bearing (B(Ph)4−) or (I−) as counter anions were examined as promising NIR light photoinitiating systems. Excellent photoinitiating

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• isoxazoline ring shields the vinyl group at C-4 from reacting with the bulky catalyst molecules (Figure 4). For the smaller Me or Et groups, this effect is relatively weak (only some reactions of (±)-5 with 7c and 7e were completely regioselective). The large Ph group, however, provided complete

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

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

• seems to favor N-1 regioisomer formation in the order t-Bu > Ph > Me > H, for both conditions A and B (Table 2, entries 1–4). Furthermore, having a sterically demanding t-Bu group at the indazole C-3 position (14) gave the N-1 substituted regioisomer 29 exclusively under both conditions A and B

• regioisomeric N-1/N-2 distribution indicated that steric bulk likely plays a significant role in determining N-1 regioselectivity. For example, the ratio of N-1/N-2 increases in the order of increasing steric bulk at the indazole C-3 position (H < Me < Ph < t-Bu). However, when the former protocol (conditions A

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• have been used as additives in these reactions and are suggested to act as ligands, assist proton transfer and promote the formation of oligovanadates by decreasing the pH value of the solution. The mechanisms of some vanadium-mediated oxidation reactions of alkanes have been studied, most of them

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

• incorporated into TFOs all induced excellent triplex stability at pH 7.0 [94] (Table 6). To circumvent the laborious work related to the monomers described above, post-ON conjugation via click-chemistry was utilized to attach two different spermidine analogues, carrying either two (56) or three (57) positive

• ’-aminoalkylated-LNA monomers [94]. The triplex stability of the monomers was determined, and the spermidine variant carrying three cationic charges (57) had the highest triplex stabilizing effect [95]. Interestingly, at biologically relevant pH (7.0), two incorporations of the nor-spermidine variant (53) [94

• - (monomer 71) and N-methyl-2-(dimethylamino)ethyl (monomer 72) phosphoramidate linkages [106]. How these N-alkylated phosphoramidate-linked ONs interacted with the complementary DNA was highly dependent on the ionic strength and the pH of the relevant medium. An inverse effect between hybridization

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• the GT concentration at sub-lethal levels via redox cycling and S-methylation of active disulfides in GT, respectively [117][118]. Furthermore, in terms of exogenous factors, not only GT itself but several other biotic and abiotic factors, including neutrophilic granulocytes, media composition, pH

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

• species tested in our study (Table 2). However, the differences in the literature may arise from the use of different strains, volatile collection methods or variation in age, growth medium and environmental conditions, such as moisture, pH, temperature, and nutrient levels, or co-cultivation [27][41][67

• diameter) growing on PDA. The mycelium was flash frozen in liquid nitrogen and ground using plastic pestles in 1.5 mL Eppendorf tubes. After homogenization of the mycelium, 500 µL extraction buffer (100 mM Tris HCl, pH 8; 10 mM EDTA, pH 8; 2% w/v SDS) and 100 µL proteinase K (Sigma) were added and the

• rpm (10 min), dried, and finally dissolved in 50 µL Milli-Q water (pH 6). DNA concentration and purity were determined with a NanoDrop 2000c spectrophotometer (Peqlab Biotechnology AG, Erlangen, Germany). The primer pair ITS1F and ITS4 (Supporting Information File 1, Table S2) was used to amplify the

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• [1]. Even with the additional lysine, the solubility of PNA decreases as the polymer length increases. PNA solubility in the HEPES buffer at pH 7.3 and 37 °C is estimated to be in the 0.1–0.5 mM range [12][13]. The hydrophobic nature and lack of electrostatic repulsion of the PNA backbone favors

• Rozners and co-workers showed that PNAs as short as hexamers formed strong and sequence specific triplexes at pH 5.5 [27]. Later studies using nucleobase-modified PNA (vide infra) confirmed that PNA had >10-fold higher affinity for dsRNA than for the same sequence of dsDNA [28][29][30][31]. While parallel

• -bonding (Figure 6) [94]. A significant bottleneck for triple helix formation is the requirement for cytosine protonation to form the natural C+•G–C triplet. Because of the low pKa of cytosine (≈4.5), formation of the C+•G–C triplet is unfavorable at physiological pH, which severely destabilizes the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• reaction between 54 and 55 was performed in anhydrous methanol under an argon atmosphere to construct 56. The study on the in vitro drug release showed enhanced drug release at an acidic pH value in comparison to a neutral pH value. Importantly, the amount of DOX required for MCF-7 cells was decreased