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

• pyrazolone-enol intermediates to the N–N double bonds of azonaphthalenes [70]. On the other hand, N-arylcarbazole frameworks are also abundant in pharmaceuticals, agrochemicals, natural products, and functional OLED materials [71][72]. Therefore, the construction of axially chiral N-arylcarbazoles is

• hydrogen bonds. Axially chiral allenes and derivatives occur in overwhelming numbers in natural products, pharmaceuticals, functional materials, and useful intermediates in organic synthesis [101]. Therefore, great efforts have been made to synthesize these axially chiral scaffolds [102]. In this regard

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• results in the formation of the 1,3-oxathiolane species 63 (Scheme 20). Enzymatic approaches 1,3-Oxathiolanes have shown broad biological activities, including the most important intermediates in the synthesis of the pharmaceuticals lamivudine (1) and emtricitabine (2), which have been approved as drugs

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

• -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

• effective but is below the level considered toxic [85]. Drug-delivery systems (DDS) demand safe and effective treatment, and in the majority of cases a long-term target specific treatment would be favoured over general multi-dose pharmaceuticals. Cryogels have been identified as a good material of choice

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

• ; Morita–Baylis–Hillman carbonates; Introduction Pyridines are among the most important heterocyclic structural moieties in many biologically active natural products, pharmaceuticals, and agrochemicals [1][2][3]. Therefore, the development of efficient strategies for functionalized pyridine derivatives

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• in many natural products, pharmaceuticals, and bioactive molecules. For instance, some pyridine derivatives have been used for therapy of HIV, cancer, inflammation, microbial infection and so on [1][2][3][4][5]. In addition, it is also an important synthetic unit, which is frequently used as catalyst

• -heterocycle that is widely used in pharmaceuticals, photoelectric materials, and functional materials [20][21][22][23]. Many pyrrole derivatives play a significant role in the life science and medicine domains due to the good bioactivities, such as antitumor, anti-HIV, and anti-HSV-1 activity [24][25][26][27

• organic molecules can efficiently modify the physical, chemical, and biological properties of the compounds. A trifluoromethyl-substituted pyrrole unit is widely present in many natural compounds and pharmaceuticals with high biological activity. Based on our previous study on the construction of

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

• design new synthetic methodologies for reproducing these natural products and their analogues as well as to develop new pharmaceuticals from them. Structures of brevipolides A–O (1 – 15). Retrosynthetic analysis of brevipolide H (8) by Kumaraswamy. Attempt to synthesize brevipolide H (8) by Kumaraswamy

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

• this compounds are required. In this regard we suggested the modification of the alcohol tail of metronidazole by incorporating an N-heterocyclic moiety. Nitrogen-containing heterocycles play a vital role in agrochemicals and pharmaceuticals [3]. Among these heterocyclic systems, the 1H-1,2,3-triazoles

• are very important in organic chemistry due to their broad spectrum of applications in biochemical, biomedicinal, pharmaceuticals, and materials sciences [4]. Their chemistry underwent a substantial growth over the past decades [5]. They are widely used in industrial applications such as photographic

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

• of synthetic routes for modern pharmaceuticals [21][22]. Over the past two decades, nickel has emerged as an attractive alternative to palladium due to its relative earth-abundance, less toxicity, and inexpensiveness. Despite the fact that the nickel-catalyzed cross-coupling reactions represent a

• optimal to furnish the desired cross-coupled products 37 in satisfactory yields. Furthermore, the method proved applicable to the late-stage diversification of bioactive molecules, pharmaceuticals, and agrochemicals as aryl coupling partners (Scheme 21) [77]. The authors proposed a catalytic cycle that

• under slightly modified reaction conditions with exclusion of the nickel catalyst (Scheme 36) [113]. Acylation The ketone motif is an important functional group in pharmaceuticals, agrochemicals, and functional materials [114][115][116][117]. Hence continuous efforts devoted to developing a convenient

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

• industrial applications in coating materials, cosmetics and pharmaceuticals [211]. Owing to their superior biological and mechanical properties, chitin and chitosan are used in fibers, gels, sponges, films, beads, and nanoparticles [212]. Tunable stiffness, solubility, and transparency can be obtained by

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

• iron-based small molecule catalyst and hydrogen peroxide as oxidizing agent (Scheme 25A and B) [156]. This pioneering methodology changed the way how complex molecules and pharmaceuticals are synthesized, by using the steric and electronic properties of the substrates to achieve selectivity, without

• co-workers described the deuteration of several pharmaceuticals via an Fe-catalyzed C–H activation protocol (Scheme 29A and B) [161]. The site selectivity of the bulky iron catalyst was orthogonal to conventional iridium catalysts used in deuterium labelling experiments, allowing the

• functionalization of complementary positions in several molecules of medicinal importance. Using molecular deuterium gas, the deuterium exchange occurred at different positions in small molecules in different proportions and satisfactory yields. Late-stage site-selective deuteration of pharmaceuticals like

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• salt; fluoropyridinium salt; fluorosulfonimide; Introduction Fluorinated organic compounds occupy an important position in pharmaceuticals [1], agrochemicals [2], and materials [3]. Especially, in the first two areas, the presence of fluorine has attracted attention during the last decades. Nowadays

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• a valuable route to mono- and disubstituted imidazoles. Keywords: Asmic; cyclization; imidazoles; isocyanides; nitriles; Introduction The imidazole core is the seventh most prevalent heterocycle among nitrogen-containing pharmaceuticals [1]. The privileged efficacy of imidazoles emanates from the

• central role of histidine in biological machinery, particularly as a base at enzymatic active sites [2]. As histidine mimics, imidazole-containing pharmaceuticals are often only N-substituted, as in the fungicides ketoconazole and econazole (Figure 1) [3], or disubstituted as illustrated by the anesthetic

• etomidate [4] and the antileukemia agent nilotinib [5]. The outstanding and diverse bioactivity of imidazole-containing pharmaceuticals [6], as well as their role as ligands for transition metals [7], and organocatalysis [8], has stimulated an array of creative syntheses [9][10]. Among the numerous routes

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• affinity; cannabinoid receptors; diindolylmethane; unsymmetrical 3,3'-diindolylmethane; Introduction Diindolylmethanes (DIMs) represent an important class of indole alkaloids, that are constituents of pharmaceuticals [1][2][3][4][5][6][7] and agrochemicals [8][9]. DIM derivatives possess a variety of

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

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• photocatalysis; recyclable; Introduction Nitrogenous heterocyclic compounds, such as indolines [1][2][3][4], oxindoles [5][6][7], isoquinolinones [8][9][10], and isoquinolinediones [11][12], are pivotal structural motifs in numerous pharmaceuticals, agrochemicals, and bioactive natural products. The oxidative

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

Highly regio- and stereoselective phosphinylphosphination of terminal alkynes with tetraphenyldiphosphine monoxide under radical conditions

• Dat Phuc Tran,
• Yuki Sato,
• Yuki Yamamoto,
• Shin-ichi Kawaguchi,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 866–872, doi:10.3762/bjoc.17.72

• derivatives having various substituents on the ethylene moiety. In particular, synthetic methods that do not use metal catalysts and reagents are expected to be very effective in manufacturing precision materials and pharmaceuticals [32][33][34][35][36][37]. To develop metal-free methods for the synthesis of

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

• pharmaceuticals and biologically active molecules (116–118) [103]. Similarly, heterocycles having pyridone nucleus are pharmacologically important as they can act as potent anticancer (119), antibacterial (120) and antiviral agents (121, Figure 9) [104][105][106]. Shamsuzzaman and co-workers [107] demonstrated

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• potential large-scale preparations. Thioamides are highly attractive molecules in pharmaceuticals, agrochemicals, electronic chemicals, and materials sciences [17][18][19][20][21][22][23][24][25][26][27]. In coordination chemistry, pincer-type ligands containing a thioamide motif were shown to exhibit

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• considerable attention as they are widespread in natural products, as well as in pharmaceuticals, agrochemicals, and organic materials. Among the π-CPHs, pyridazines and pyrroles have important roles [17][18][19][20][21][22]. Although there are very few pyridazine ring-containing compounds isolated from nature

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• . Keywords: alkenes; difunctionalization; metal-free; photoredox; trifluoromethylthiolation; Introduction The incorporation of fluorine atoms into drug molecules will significantly enhance the physical, chemical, and biological properties of the pharmaceuticals [1][2][3][4][5][6]. Modifying drug candidates

• (πR = 1.44), compared with CF3 (πR = 0.88) and SCH3 (πR = 0.61), which could improve the pharmaceuticals’ ability to cross lipid membranes [9][10]. Along these lines, the introduction of the SCF3 group into small molecules has attracted great attention in organofluorine methodology [11][12][13][14][15

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• natural products [1][2][3][4], agrochemicals and pharmaceuticals having potent biological activities, such as antimalarial, antibacterial and anticancer activities [5][6][7][8][9][10][11]. Due to their wide range of applications, selective functionalization of quinolines at various positions has gained

• has also attracted considerable attention due to the importance of the 2-aminoquinoline motif in medicinal chemistry and pharmaceuticals [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Some of the representative examples of biologically relevant derivatives containing a 2

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• Wilfred J. M. Lewis David M. Shaw Jeremy Robertson Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, United Kingdom Vertex Pharmaceuticals (Europe) Ltd., 86–88 Jubilee Avenue, Milton Park, Abingdon, OX14 4RW, United Kingdom current

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• large number of anthropogenic compounds, in particular pharmaceuticals, agrochemicals and anti-stain/anti-stick compounds (per- and poly-fluorinated alkyl substances, PFAS). When these compounds come into contact with microorganisms, there is a high likelihood that they will be biotransformed to some