A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• , with synthesis scale-up tolerated under mild conditions. To facilitate the construction of various functional scaffolds using this system, lactones were subsequently α-functionalized via the corresponding α-bromolactones using this two-phase system. Interestingly, 3b synthesized using this method was

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• preparation of highly valuable diarylmethyl sulfones are relatively scarce [24]. In addition, the important link between structural diversity and complexity with bioactivity represented by sulfones has led to the goal of developing strategies to as many these pivotal scaffolds as possible. Isocyanide is an

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• ; Introduction In recent years, metal complexes with biological activity are of paramount relevance in medicine as valuable alternatives for the classical pharmaceuticals based on organic compound scaffolds. In this line, metal complexes incorporating an amphiphilic character (also called metallosurfactants

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• trifluoromethylated hybrid system comprising the Schiff base scaffolds from some 6-aminoquinolines and salicylaldehyde derivatives in order to analyze and evaluate their photophysical, photostability, and antioxidant properties for possible future applications in the pharmacological areas or materials sciences

• here highlights their potential as dyes in photobiological applications. Conclusion In conclusion, we reported the synthesis and photophysical and antioxidant properties of a new series of ten novel Schiff bases 3. The scaffolds 3 could be synthesized by a simple condensation reaction between 6

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• compounds to provide novel, sp3-enriched scaffolds with increased propensity to generate potent lead structures with favorable physicochemical properties [1][2][3][4]. In light of this, synthesis of compounds that are close analogs of natural compounds is an important task for the synthetic organic

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• , axially chiral allenes and spiranes [25] are well-known scaffolds widely used in natural products, ligands, organocatalysts, and functional materials as well as versatile chiral building blocks in organic synthesis [14][26][27]. Chiral phosphoric acids represent an important and widely used class of

• provide easy access to the privileged NOBIN (2-amino-2’-hydroxy-1,1’-binaphthyl) structures 41. The additional insights into the origins of enantiocontrol were described by DFT calculations. Owing to the presence of axially chiral indole-based biaryl scaffolds such as naphthylindoles and phenylindoles in

• also achieved the first catalytic asymmetric construction of axially chiral 3,3’-bisindole scaffolds 49 bearing both axial and central chirality by employing the CPA-14-catalyzed asymmetric addition reaction of 2-substituted 3,3’-bisindoles 47 to isatin-derived 3-indolylmethanols 48. The isatin-derived

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

• Pratibha Sharma Raakhi Gupta Raj K. Bansal Department of Chemistry, The IIS (deemed to be University), Jaipur 302 020, India 10.3762/bjoc.17.173 Abstract Nitrogen-containing scaffolds are ubiquitous in nature and constitute an important class of building blocks in organic synthesis. The

• . Review In the present review, the known stereoselective syntheses of pharmacology-oriented nitrogen containing heterocyclic scaffolds via non-covalent bonding and covalent bonding organocatalytic aza-MRs has been systematized. This classification is especially useful for researchers to understand both

• -containing chiral scaffolds of wide applications in the fields of pharmaceuticals, organic synthesis building blocks and accessible catalysis continues to attract attention of the chemists. During the last two decades, many new chiral organocatalysts have been developed for accomplishing these reactions with

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

• properties induced is used when transferring from room temperature to another environment (i.e., body temperature). This leads to potential applications such as injectable biodegradable scaffolds in tissue engineering, or utilising the changing surface properties for in vitro cell culture applications [36

• material could be a potential for targeting release in the colon. 4. Other cryogel applications For cryogel biomedical applications not discussed in section 5, including cell separation, tissue engineering scaffolds, bioreactors and capturing of target molecules, the reader is directed to a recent review

• millimetre-sized defects (common in most in vivo tissue-engineering work in small animal models) [64]. Kim and co-workers reported a method in 2009, whereby a 3D-plotting system was coupled to a cryogenic refrigeration system [65][66]. Using these systems 3D scaffolds were prepared by printing collagen

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

• precursors have also been widely explored in the past decades. These reactions typically proceed under the catalysis of a nucleophilic tertiary amine or phosphine, and no metal catalysts are needed, which makes this strategy more synthetically useful for the construction of allyl-substituted scaffolds

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

• -spectrum biological functions which include antifungal [9][10][11] and antibacterial activities [12][13][14]. Natural product scaffolds isolated from species of this genus have contributed immensely as leads to drug discovery and development [15]. For instance, clofazimine [16], the antimycobacterial agent

• of Staphylococcus aureus with MIC values ranging from 0.06 to 0.25 µg/mL. Mupirocin was later developed for topical usage [19][20][21][22]. Several siderophores of hydroxamate, catecholate or phenolic scaffolds such as cepabactin [23], pyochelin [24][25], pyoverdines [26], vulnibactin [27], and

• compounds 1–5 was assigned as ʟ, based on the derivatization with Marfey’s reagent of compound 2 and 4 hydrolysates, which represented the two distinctive structural scaffolds and chemical shifts followed by HPLC analysis of the derivatized amino acid residuals in the hydrolysate and threonine standards

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

• metronidazole scaffolds are known to have a large range of biological activities including tumorhypxia agents [8], antiprotozoal activity [9], antimicrobial [10], antitumour [11], carbonic anhydrase IX inhibitors [12], trichomonas vaginalis activity [13], antileishmanial agents [14] (Figure 2). We have recently

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• with high selectivity using this strategy. In these transformations, two Hg-carbene intermediates were proposed to be involved (Scheme 52). Mercury-catalyzed reactions were also well known for the formation of various complex scaffolds like tricyclic pyrazinones from the corresponding starting

• . Synthesis of tricyclic heterocyclic scaffolds. HgCl2-mediated cyclization of 2-alkynylphenyl alkyl sulfoxide. a) Hg(OTf)2-catalyzed cyclization of allenes and alkynes. b) Proposed mechanism of cyclization. Stereoselective synthesis of tetrahydropyran derivatives. a) Hg(ClO4)2-catalyzed cyclization of α

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• ]. In this review, we highlight the developments in C–H activation enabled by nickel photocatalysis. Review Arylation The arylation of C(sp3)‒H bonds constitutes a potential tool for the rapid diversification of simple organic molecules into valuable scaffolds [48][49][50][51][52]. In 2014, Doyle

An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• photopolymerization for the hydrophilic modification of microfiber scaffolds obtained from hydrophobic medical-grade poly(ε-caprolactone) via melt-electrowriting. Contact angle measurements and Raman spectroscopy confirms the formation of a more hydrophilic coating of poly(2-hydroxyethyl methacrylate). Apart from

• final fiber diameter. The direct-writing onto a flat collector or on a rotating/translating mandrel enables the printing of flat [11][12] or tubular [13] scaffolds, respectively. While medical-grade poly(ε-caprolactone) (PCL) is the most commonly used material for MEW, due to its favorable thermal and

• the coating of 3D printed PCL microfiber scaffolds, investigate the range of suitable parameters and characterize the change in the properties of the coated scaffolds. PCL scaffolds with a hatch spacing of either 150 µm or 500 µm were fabricated, with the fiber diameter being 12.1 ± 3.3 µm. The

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

• Abstract This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with

• multiple stereogenic centers. The synthesis involved selective cycloadditions, with subsequent ROM of the formed cycloalkene-fused isoxazoline scaffolds and selective CM by chemodifferentiation of the olefin bonds of the resulting alkenylated derivatives. Various experimental conditions were applied for

• -metathesis (ROCM) have found high utility in the creation of C=C bonds and in the synthesis of a number of organic molecules, functionalized scaffolds or various building blocks. The efficient catalytic activity and remarkable functional group tolerance of commercially available versatile Ru-based olefin

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• Natalia M. Moreira Lorena S. R. Martelli Arlene G. Correa Centre of Excellence for Research in Sustainable Chemistry, Department of Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP – Brazil 10.3762/bjoc.17.128 Abstract Coumarin derivatives are essential scaffolds in medicinal

• % ee (Scheme 37). Furthermore, the natural product was synthesized in seven steps with 14% overall yield. Conclusion Coumarin derivatives are important scaffolds for synthetic and medicinal chemistry. These structures have an interesting reactivity and can be used in diverse organic reactions, for

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

• to be, there is still a demand for applying this relevant methodology to obtain new compounds with known pharmacological properties. However, several molecules based on structural scaffolds related to important biological activities have been successfully achieved via scandium-catalyzed C–H

• ]. The desired aminoindane derivatives were obtained with good regio- and enantioselectivity, (product A/product B was observed in a ratio higher than 19:1, Scheme 5C). It is worth mentioning that aminoindanes are scaffolds also present in biologically active molecules that may present, for example

• highly site-selective and wide functional-group tolerant reaction. To test this protocol versatility over biologically relevant scaffolds, a COCF3-leelamine analogue 48 with two sterically differentiated benzylic sites was selectively aminated at the secondary benzylic site. After Tces deprotection, the

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

• charges, onto the 2’-amino-LNA scaffolds. This was demonstrated to be a successful design as both monomers showed very high duplex stabilizing properties towards RNA (Tm +10.0 °C) and DNA (Tm +8.5 °C). Additionally, nuclease resistance was shown to be high [95] which was in agreement with other 2

• increased target binding affinity is usually seen relative to modifications on the furanose ring (minor groove). However, when the 2’-amino-LNA scaffolds is used, a very high duplex stability is seen irrespectively of the target (DNA or RNA), as a synergistic effect between the locked sugar conformation 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

• alkynylations of bioactive structural motifs are rare [63]. In 2017, the Ackermann group disclosed a late-stage Mn(I)-catalyzed C–H alkynylation of various complex peptide scaffolds [64]. As shown in Scheme 9, manganese(I) catalysis remarkably resulted in racemization-free alkynylation, representing a step

• acetate as the base to deliver the corresponding peptide–sugar conjugates 31 at the late stage. Notably, the chemoselective glycoconjugation strategy was compatible with various sugar scaffolds, affording glycotryptophans bearing either furanose or pyranose motifs. In addition, a brevianamide F analogue

• =NTces were used. Mn-catalyzed C–H methylation of heterocyclic scaffolds commonly found in small-molecule drugs. aDAST activation. bBF3⋅OEt2 activation. c1 mol % of (S,S)-Mn(CF3–PDP) was used. Examples of late-stage C–H methylation of bioactive molecules. aDAST activation. bFor insoluble substrates

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

• using aliphatic secondary (aromatic) amines. In the next step, the effect of R1 and R2 groups on the triazole ring was also screened. These groups could be aliphatic or aromatic scaffolds. In almost all cases, the desired triazole compounds were formed in good to high yield. The short reaction time

• . Moreover, TMS-substituted alkyne was suitable for this Huisgen reaction to achieve the desired triazole product. Next, some triazene scaffolds, such as dimethylamino-, pyrrolidine-, piperidine-, morpholine-, and piperazine-derived triazenes were screened. Aryl azides containing Br, I, Me, and MeO as well

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• ] auxiliaries (Figure 1a). Besides, the cobalt(II)- [31] or nickel(II)-catalyzed [32][33], pyridine oxide (PyO)-directed tandem alkynylation/annulation was realized by Niu and Song et al., which also provided the 3-methyleneisoindolin-1-one scaffolds (Figure 1b). Notably, a sustainable cupraelectro-catalyzed

• , the robust copper-mediated C−H activation featured remarkable compatibility of synthetically meaningful functional groups, giving facile access to valuable 3-methyleneisoindolin-1-one scaffolds. Experimental General information Yields refer to isolated compounds, estimated to be >95% pure as

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -promoted condensation of a homoallylic alcohol and an aldehyde to give an oxocarbenium ion, which is then reacted with an olefinic/alkynic bond generating a carbocation that undergoes a Friedel–Crafts reaction. Given the potential value of tetralin-2-ol scaffolds to drug research programs, we decided to

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• extreme thermal conditions with the use of corrosive reagents. Much later, Larock and co-workers developed a Pd/Cu-catalyzed imino-annulation of internal alkynes [15], which paved the way for transition-metal-catalyzed cyclizations as easy access to these scaffolds. Notably, the gold-catalyzed tandem

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• terminal carbons only. Double-headed nucleosides are synthetically derived nucleoside scaffolds that are known to impact significantly secondary structures in nucleic acids [29]. Some oligonucleotides containing a particular double-headed nucleotide monomer have been found to form a three-way junction