(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• , respectively (Scheme 12B) [58]. Saponification of the ester moieties in these species followed by Curtius rearrangements then led to amines 114 and 116. Non-natural amino acid derivatives 113 and 117 are intermediates prepared using these methods that could be of interest to medicinal chemistry. Alcohol 111

• the goal of this review but a number of pertinent examples will be highlighted (Figure 28). Bridge-substituted trisubstituted BCPs are potentially powerful building blocks offering unique substituent geometries for medicinal chemistry. A limited number of routes are available to these structures. Qin

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• , tylactone (39), and a dimethylamino sugar, which are synthetically challenging. Therefore, the synthesis and evaluation of tylosin-related macrolides are hot topics in medicinal chemistry [66][74]. With the experience in pikromycins synthesis, Sherman and co-workers investigated the capabilities of two

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• owing to their wide applications in medicinal chemistry [1][2][3][4][5]. γ- and ε-AA derivatives are widely distributed in peptide natural products, bioactive molecules, and drugs, such as pregabalin, baclofen, ε-aminocaproic acid and lysine (Scheme 1a) [6][7][8][9][10][11][12]. The number of reported

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• ., Saint Petersburg 191036, Russian Federation Department of Medicinal Chemistry, Institute of Chemistry, Saint Petersburg State University, 26 Universitetskiy pr., Peterhof 198504, Russian Federation 10.3762/bjoc.20.48 Abstract A facile approach to novel medicinally relevant spiro heterocyclic scaffolds

• alcohol followed by base-promoted cyclization. The procedures developed allow to obtain derivatives of such sought-after scaffolds in the field of medicinal chemistry as Δα,β-butenolides, tetrahydrofurans, and pyrans spiro-conjugated with a pyrrolidine ring. The tandem approach proposed is characterized

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• highest fungicidal activity [11]. Brønsted or Lewis acid catalysis – conventional synthetic methods The indole moiety is part of many natural products, agrochemicals, and pharmaceuticals. In medicinal chemistry, indole and its derivatives are considered important compounds, since they exhibit valuable

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• holds significant promise for applications in the fields of medicinal chemistry, materials science, and photovoltaics. In this study, we investigate the regioselectivity of the rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions between diynes and C70 as a novel procedure for generating C70 bis

• been proposed in different fields such as medicinal chemistry [2][3][4][5][6], materials science [7][8], energy production, storage, and delivery [9][10][11][12][13], and electronics and optoelectronics [14][15][16]. Despite fullerenes having immense promise in all of these areas, their practical

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• Grigory Kantin Pavel Golubev Alexander Sapegin Alexander Bunev Dmitry Dar'in Saint Petersburg State University, Saint Petersburg, 199034, Russian Federation Medicinal Chemistry Center, Togliatti State University, Togliatti, 445020, Russian Federation Saint Petersburg Research Institute of

• Phthisiopulmonology, Saint Petersburg, 191036, Russian Federation Department of Medicinal Chemistry, Institute of Chemistry, Saint Petersburg State University, 26 Universitetskiy prospekt, Peterhof 198504, Russian Federation 10.3762/bjoc.19.136 Abstract A technique has been proposed for incorporating a heterocyclic

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• Xiaofeng Zhang Xiaoming Ma Wei Zhang Center for Green Chemistry and Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA Department of Medicinal Chemistry, Cerevel Therapeutics, 222 Jacobs St Suite 200, Cambridge, MA 02141, USA School of

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• ; gem-difluoroalkenes; organic azides; Introduction gem-Difluoroalkenes and their synthetic preparations soared in the last decade, driven by the high demand for carbonyl mimics in medicinal chemistry and drug discovery [1]. Although a wide array of functionalization strategies for gem-difluoroalkenes

• -trisubstituted-1,2,3-triazoles, with a pendant morpholine at the C-4 position are formed with complete regiocontrol via β-fluoride elimination in an SNV-like transformation (Figure 1C). 1,2,3-Triazoles are a privileged scaffold in medicinal chemistry with a myriad of pharmacological activities against cancer [11

• -withdrawing group, such as trifluoromethyl (4h), was obtained in 44% yield. When morpholine was replaced with piperidine (5a) or seven-membered azepane (5b) as a solvent, a decreased yield was observed (30–42%). The addition of piperidine offers an advantage in expanding the substrate scope to medicinal

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• synthesis, medicinal chemistry, and materials science [1][2][3][4][5]. For example, they are used in the treatment of cancer [6][7][8], inflammation [9][10][11], human immunodeficiency virus [12][13], Alzheimer’s and Parkinson’s diseases [14][15]. Scheme 1 shows selected examples of sulfur-containing

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• . This reaction has the advantages of using readily available materials, simple reaction conditions, satisfactory yields, high diastereoselectivity and atomic economy, which enable this reaction potential synthetic applications in heterocyclic chemistry and medicinal chemistry. Experimental General

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• unprecedented synthetic reactivity of the electron-deficient alkynes, but also provides efficient synthetic methodologies for complex nitrogen-containing heterocycles. The potential application of this reaction in organic synthesis and medicinal chemistry might be significant. Experimental General procedure for

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• . This methodology has been applied to diverse areas of chemistry, including natural product synthesis [45][46], medicinal chemistry [47][48], polymer chemistry [49][50] and porphyrin chemistry [51][52][53]. In recent years, green chemistry has become a widely used method for organic synthesis in order

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• Haritha Sindhe Malladi Mounika Reddy Karthikeyan Rajkumar Akshay Kamble Amardeep Singh Anand Kumar Satyasheel Sharma Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research - Ahmedabad, Gandhinagar, Gujarat, 382355, India Department of Natural Products

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• novel quinoline construction and functionalization techniques resulting in new or rare derivatives [17][18][19][20][21][22][23][24][25][26] is an important mission in the field of drug discovery and medicinal chemistry. The sulfonamide group is a known privileged motif in drug design often serving as a

• of the approach devised is that all starting materials including sulfonyl compounds are easily accessible. Furthermore, the preparation techniques are flexible concerning the variations of substituents, which is of high importance for the potential medicinal chemistry applications. Scheme 2

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• –Bienaymé reaction; imidazo[1,2-a]pyridine; isocyanide; multicomponent reaction; peptidomimetic; Ugi reaction; Introduction The use of isocyanide multicomponent reactions (IMCR) to prepare biologically active compounds is one of the most promising tools in modern organic and medicinal chemistry. Therefore

• a given reaction makes it possible to very quickly not only to insert important pharmacophoric fragments, but also to create a wide chemical space for the search for lead structures to solve problems of medicinal chemistry. Examples of drugs synthesized by MCR clearly demonstrate the immense

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The

• popular in medicinal chemistry and pharmacology as potential biologically active compounds. In particular, PBTAs were found to be promising inhibitors of centromere-associated protein E (CENP-E) (Figure 1), which is demanded for the development of targeted cancer therapy [1]. Furthermore, candidate

• ][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] to meet the needs of medicinal chemistry and pharmacology for PBTAs containing diverse substituents. In general, these synthetic strategies can be divided into four groups. The first group of approaches

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

•  44B). In the end, protonation of the Li enolate affords the spiroindane boronate. Due to their paramount role in the fields of bioactive natural products and medicinal chemistry, there is a growing interest in enantioenriched cyclobutanes. Recently, the group of Hall was engaged in developing

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• medicinal chemistry. Owing to the strong absorption in the visible region, these 18π-electron systems also demonstrate excellent photoluminescence properties. Therefore, porphyrin hybrids have been widely used as efficient sensitizers for PDT applications and dye-sensitized solar cells (DSSCs). Because the

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• ]. Substituted pyrazoles are also of considerable interest because of their synthetic utility as chiral auxiliaries [32], synthetic reagents in multicomponent reactions [33][34], and guanylating agents [35]. The installation of a thioamide functionality has attracted an immense attention in medicinal chemistry

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• with fluoroalkyl moieties led to a reduction or loss of activity at the tested concentrations. These data indicate that additional medicinal chemistry efforts involving H-8 replacement with fluoroalkyl groups for this OSM series is not warranted. Experimental General procedure for Diversinate

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• newly prepared thiophosphorus acids were not efficient in the asymmetric transfer hydrogenation of 2-phenylquinoline. However, they may find application in other model reactions. These days, stereoselective syntheses incorporating “green" chemical considerations are of utmost importance in medicinal

• chemistry and beyond. Quantum chemical calculations are a great support for organic chemists when exploring structures, reactivities, and mechanisms. In this thematic issue, the Diels–Alder cycloaddition of 2-phosphaindolizine, 1-aza-2-phosphaindolizine, 3-aza-2-phosphaindolizine, and 1,3-diaza-2

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• Anastasia Vepreva Alexander Yanovich Dmitry Dar'in Grigory Kantin Alexander Bunev Mikhail Krasavin Saint Petersburg State University, Saint Petersburg 199034, Russian Federation Academic Gymnasium of Saint Petersburg University, Saint Petersburg 199155, Russian Federation Medicinal Chemistry

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• Ksenia Malkova Andrey Bubyrev Vasilisa Krivovicheva Dmitry Dar'in Alexander Bunev Mikhail Krasavin Saint Petersburg State University, Saint Petersburg 199034, Russian Federation Medicinal Chemistry Center, Togliatti State University,445020 Togliatti, Russian Federation Immanuel Kant Baltic Federal

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• pyrrolopyrimidines) are N-heterocycles that have become an indispensable part of research in medicinal chemistry [1][2][3]. Especially, derivatives of 3-deazaguanine (imidazo[4,5-c]pyridines) [4], 7-deazaguanine/-hypoxanthine (pyrrolo[2,3-d]pyrimidines) [5][6], and 9-deazaguanine/-hypoxanthine (pyrrolo[3,2-d

• diversification and applications in medicinal chemistry. They will also be useful for nucleosidation reactions to prepare the corresponding nucleosides in straightforward manner. Experimental General. Chemical reagents and solvents were purchased in the highest available quality from commercial suppliers (Merck

• Raphael Bereiter Marco Oberlechner Ronald Micura Institute of Organic Chemistry, Center for Molecular Biosciences, Innsbruck (CMBI), Innrain 80-82, 6020 Innsbruck, Austria 10.3762/bjoc.18.172 Abstract Imidazopyridines and pyrrolopyrimidines are an important class of compounds in medicinal