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

• target product 69 (Scheme 23). This catalytic approach encompasses a wide range of substrates and functional groups to construct atropisomeric N-arylbenzimidazoles that are widely used in natural products, biologically active molecules, ligands, and catalysts. Axially chiral arylpyrroles are the core

• and could considerably improve the stereocontrol of the reaction [21]. The axially chiral arylquinazolinones form the backbones of a large number of natural products and biologically active compounds as well as chiral ligands [83]. Nevertheless, a simple chiral phosphoric acid-catalyzed

• and spiranes The enantioselective construction of spirocyclic centers is an exciting synthetic challenge that plays a prominent role in the discovery of new catalysts and complex molecules [98]. Spirocyclic frameworks are present, for example, in biologically active natural products (e.g

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• bile acids, derivatives with altered hydrophobicity are being studied [12][13][14]. The tetrazole moiety can be found in many biologically active compounds, and monosubstituted tetrazole is being used in medicinal chemistry as a bioisostere of carboxylic acid [15] because it increases the lipophilicity

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

• 108 to aliphatic α,β-unsaturated aldehydes 109 and synthesized biologically active acyclonucleoside 110 via an iminium-ion activation mechanism. The initially formed product was reduced in situ to afford the final product in 82–89% yield and 89–96% ee (Table 25) [66]. In a similar method, Joie et al

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

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

• assay against the cell proliferation of the human hormone-refractory prostate cancer cell line (PC-3). Mohapatra’s strategy to brevipolide H (8) As part of the interest in synthesizing biologically active cyclopropane-containing natural products, Mohapatra and co-workers in 2015 started their attempt to

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• , ArH), 7.62 (t, J = 7.6 Hz, 1H, ArH), 7.32 (s, 1H, ArH), 6.16 (s, 2H, Ar-CH2); 13C NMR (101 MHz, CDCl3) δ 151.7, 151.5, 148.2, 144.0, 130.3, 129.9, 128.0, 126.7, 124.3, 123.0, 122.0, 105.5, 101.9, 99.9 ppm [18]. Biologically active phenanthridines. Synthetic routes to phenanthridines via iminyl

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

• xanthenes has increased remarkably in recent years due to their wide range of biological and pharmacological properties. Xanthenes are important biologically active oxygen-containing heterocyclic compounds. These types of compounds have some biological and pharmacological properties, such as

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

• synthetic building blocks and as a common substructure in a number of biologically active molecules [1][2][3][4][5]. In addition, the lactamized derivatives of these compounds, pyroglutamates, occur in a number of well-known biologically active natural products including dysibetaine [6][7][8][9][10][11][12

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

•  4, entries 3 and 4) provides further support for the important role that tight ion pair formation plays in directing N-alkylation of the indazole scaffold. Examples of indazole natural products (1 and 2) and synthetic biologically active indazole derivatives (3–8). Observation of a 1H–13C

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

• equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C–H activation processes to obtain potentially (or proved) biologically active compounds. Keywords: bioactive compounds; C–H

• activation; 3d metals; drugs; medicinal chemistry; Introduction The discovery of new biologically active substances represents not only an advance in the chemistry field but also offers innovative chances for pharmacological and biomedical sciences. Every year, several molecules are discovered and studied

• few of them become approved, due to their toxicity or other issues related to their applicability. Therefore, synthetic methodologies that facilitate the successful production of potential biologically active molecules have a relevant role in the organic synthesis research field. One of the key

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

• biologically active small molecules and complex peptides. Keywords: bioactive molecules; 3d transition metals; late-stage functionalization; manganese catalyst; sustainable catalysis; Introduction Manganese, a 3d transition metal, allows for a potentially ideal sustainable catalytic system because of the

• strategy, is regarded as a crucial tactic in the area of natural products, drug discovery, and medicinal chemistry [7][8][9][10][11][12] as it confers an invaluable synthetic opportunity for the facile diversification of biologically active complex molecules at the late stage. In recent years, much effort

• , traps the C-centered radical, finally delivering the fluorinated product 2 or 4. Thereafter, the same group successively reported the first manganese-catalyzed late-stage 18F-fluorination of a wide range of biologically active compounds (Scheme 2) [25]. It is well known that the most utilized

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

• employing a variety of amino esters and a wide range of (hetero)aromatic and alkyl ketones. Natural products, such as 5α-cholestan-3-one and dihydrotestosterone, were also tolerated, affording a new strategy to modify biologically active compounds. Amino acids, such as tyrosine, ʟ-Phe-ʟ-Phe, glutamic acid

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

• substrate scope and functional group tolerance is highly desirable. As part of our continuous efforts to prepare biologically active DIM derivatives [38], we herein report an innovative approach to synthesize unsymmetrical 3,3'-diindolylmethanes (DIMs) with a fluoromethyl-containing quaternary carbon center

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

• decomposition of N-pyridylbenzotriazoles. Later, the reaction conditions were modified to make this reaction more versatile and operationally simple such as by the use of microwave irradiation [12]. Meanwhile, the Fischer indole synthesis was successfully extended for the synthesis of significant biologically

• active tetrahydro-γ-carboline derivatives [13][14]. A systematic assessment of the above Graebe–Ullmann and Fischer synthesis protocols revealed that these reactions are associated with i) low product yield, ii) limited scope including the use of a very specific set of substrates, and iii) involvement of

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• rearrangement; cyclocondensation; heterocycles; thiazolidine-4-one; 1,2,4-triazine; Introduction The thiazolidin-4-one heterocyclic system is a well-known, accessible and, as a consequence, a widely used pharmacophore in the chemistry of biologically active compounds possessing antimicrobial [1

• ], antituberculosis [2], anti-inflammatory [3][4], anticancer [5], antidiabetic [6][7], and antiviral activities [8]. A significant number of biologically active thiazolidines amount to their heteroannelated derivatives, namely, condensed thiazolo[3,2-a]pyrimidines [9] and thiazolo[3,2-b]-1,2,4-triazoles [10], as

• further transformations in basic media, are continuing. Biologically active compounds having thiazolidin-4-one and thiazolo-1,2,4-triazine units. 1H NMR spectra of compounds 4h and 5h in DMSO-d6 in the region of 3.5–8.8 ppm. X-ray crystal structure of compound 5i. Regioselectivity of the cyclization of 3

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

• . Asymmetric synthesis of pyrrolidines The pyrrolidine ring is more represented within natural products than the 3- and 4-membered nitrogen-containing heterocycles. This molecular array is also found in drugs and other biologically active molecules. For this reason, there are numerous examples of synthetic

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• excellent in almost every example (Table 35) [14][15]. Selected addition products were used as intermediates in the total syntheses of various biologically active compounds (Scheme 24) [14][15][16]. Catalytic systems based on different groups of ligands The use of the chiral 1,10-phenanthroline ligand L15

• system for the synthesis of intermediates of biologically active compounds [4]. Usage of a Michael addition catalysed by L9/Pd(TFA)2 in the total synthesis of (–)-ar-tenuifolene [12]. Synthesis of terpenoids by Michael addition to 3-methyl-2-cyclopentenone [13]. Rh-catalysed isomerisation of 3-alkyl-3

• arylboronic acids [59]. Attempt to use the catalytic system L2/Pd(TFA)2 for the addition of phenylboronic acid to 3-methyl-2-cyclohexenone [14]. Ring opening of an enantioenriched tetrahydropyran-2-one derivative as alternative strategy to linear products [14]. Synthesis of biologically active compounds from

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• enantioselective transformations, while the 2-phenyliminooxazolidines could be interesting in the field of antiproliferative or antioxidants studies based on our former studies on 2-imino-1,3-heterocycles [42][43]. Biologically active 2-amino-1,3-diols. NOESY experiments and X-ray structure elucidation of

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• example of a biologically active benzofuropyridine is revamilast (7), which has been used in Phase II clinical trials, studying the treatment of asthma and rheumatoid arthritis [19]. Other examples are the hydroxybenzofuro[2,3-b]pyridines 8 with efflux pump inhibitory activity useful in chemotherapy [20

• in the yield. To the best of our knowledge, this is the first procedure toward compound 13, without additional substituents on the pyridine ring. Furthermore, this method is complementary to the most common routes towards the biologically active 1-aza-9-oxafluorenes [20][21][22][23][24][25][26]. To

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

• subjecting them to the potential dipolarophile but-2-ynedionates to deliver the target molecules. Both the reactions proceeded well in water aiding in greener synthesis of biologically active molecules. The synthesized molecules exhibited significant activity against human lung cancer cell line A549. A

• 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

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

• commonly used for the synthesis of biologically active compounds having enzyme inhibition and antiviral activity [1][2], and are found in the structures of many commercially available antidepressant drugs [3][4][5][6][7][8][9][10][11][12]. In addition, dibenzosuberenone (1) and polyconjugated derivatives

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• stereospecifically new chlorocyclooctanetriols. Keywords: aminocyclitols; aminocyclooctanetriol; chlorocyclooctanetriol; cyclic sulfate; cyclitols; Introduction The synthesis of aminocyclitols has attracted attention because they contain substructures of many biologically active natural products [1][2][3]. They

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• , 12843 Prague 2, Czech Republic 10.3762/bjoc.17.58 Abstract Pyrrolidones are common heterocyclic fragments in various biologically active compounds. Here, a two-step radical-based approach to γ-lactams bearing three to four stereocenters starting from epoxides, N-allylic silylacetamides and TEMPO is

• ; electron transfer; γ-lactams; tandem reactions; Introduction Nitrogen-containing heterocycles are widely distributed in biologically active compounds [1][2][3][4]. Saturated nitrogen heterocycles such as pyrrolidines [5][6][7][8][9], piperidines, pyrrolizidines or indolizidines [10][11][12][13][14][15][16

• synthesis of functionalized γ-lactams, which can be used as building blocks for the synthesis of natural products or biologically active compounds. Experimental Tandem nucleophilic epoxide opening/Brook rearrangement/α-oxygenation (general procedure) In a similar manner as described in [74]: LiCl (252 mg, 6

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• conclusion, we have advanced the creation of a convenient tandem approach to potentially biologically active 1,2,3-triazolobenzodiazepinones. The developed synthetic procedure includes a four-component Ugi reaction followed by microwave-assisted intramolecular azide–alkyne cycloaddition and allows to build a