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

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• iminosugar derivatives may be less obvious. Several pharmaceuticals are based on this scaffold including the glucose-derived nojirimycin, an antibiotic and glycosidase inhibitor [26] and 1-deoxygalactonojirimycin, known under the trade name Galafold®, which is utilized for the treatment of the Fabry disease

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• a common strategy employed in the development of pharmaceuticals [1][2][3][4], agrochemicals [5] and materials [6]. Recent years have seen a surge in interest in emerging fluorinated motifs, which can offer improved performance over single fluorine atoms or perfluoroalkyl substituents. The

• groups (SRF, RF = CnF2n+1) have received comparatively little attention despite promising applications in liquid crystal displays [13][14], as pharmaceuticals and agrochemicals [15]. For example, analogues of the drug losartan featuring SC2F5, SC3F7 and SC4F9 groups have shown promise as treatments for

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• to be developed [14]. The formation of new C–C bonds through direct C–H bond functionalization in organic chemistry is attractive [15]. Such methodologies are omnipresent and facilitate sustainable organic transformations for the synthesis of complex natural products and pharmaceuticals. In the past

• [41][42]. However, to develop advantageous eco-friendly, atom-economical, simple, and efficient synthetic-organic processes under solvent- and catalyst-free conditions in order to synthesize highly demanding pharmaceuticals or natural products can be quite backbreaking [43][44][45]. From this

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• -analogs has become a trend to increase the properties of these valuable molecules [9]. Due to the unique properties, the SF5 group has been used in various fields of chemistry, including pharmaceuticals [10][11][12][13][14][15][16], agrochemistry [17][18][19][20], and materials sciences [21][22][23][24

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• ]. One utility of the CF3 group is the replacement of a methyl group in biologically active molecules to avoid the metabolic oxidation of a reactive methyl group in the parent molecules [8]. It should be noted that 19% out of 340 marketed fluoro-pharmaceuticals [4] and 42% out of 424 registered fluoro

• -agrochemicals [5] contain a CF3 moiety in their structures (Figure 1), but this motif has never been found in nature [9]. Several notable examples of CF3-containing pharmaceuticals and agrochemicals include cinacalcet, efavirenz, travoprost, pexidartinib, fluoxetine, and upadacitinib (Figure 2) [4][5

• flash chromatography (n-hexane) to afford the title compounds. Ratios of CF3-containing drugs in marketed fluoro-pharmaceuticals and registered fluoro-agrochemicals in the world. Selected examples of CF3-containing biologically active molecules. Transformation of acyl fluorides to trifluoromethyl

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• agrochemistry. Even if, to date, there are no CF3Se-containing pharmaceuticals registered [15], a recent work has demonstrated the promising development of trifluoromethylselenolated nonsteroidal anti-inflammatory drugs as potential anticancer drugs [34]. Over the last years, trifluoromethylselenolation

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• motif [20][21][22][23], the development of cost-effective methods to access functionalized pyrrole skeletons has remained an ongoing challenge. N-(Hetero)aryl-4,5-unsubstituted pyrroles are one of the most important types of pyrroles, which are frequently used as a core scaffold in pharmaceuticals

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• ]. A wide range of pharmaceuticals, agrochemicals, and other biologically active compounds are prepared using different types of (3 + n) cycloadditions, mainly with alkenes and alkynes [3][4][5][6][7]. For example, N,N'-cyclic azomethine imines are precursors of biologically active bicyclic