High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• conducting polymers or scaffolds for drug synthesis. Among them, 1,3-dihydrobenzimidazoles are widely found in many materials, drug candidates, and catalysts. For instance, they can be used in organic light-emitting diodes (OLEDs) [38], as water-soluble antitrypanosomatid agents [39], or in the synthesis of

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• disulfides from sodium sulfinate without the use of additional redox reagents remains a challenging task. 3-Sulfenylchromones are an important class of heterocyclic compounds with unique skeletons in nature that play an essential role in drug synthesis and development. To synthesize these compounds, direct C

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• -substituted 1H-imidazo[1,5-a]imidazole scaffold. This scaffold has a significant relevance in drug synthesis and was not deeply studied yet. As depicted in Scheme 22, 5-amino-1H-imidazole-4-carbonitrile (57) was used as heterocyclic amidine, to obtain the desired bicyclic adducts 58. The solvent choice was

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• catalyst. The authors demonstrated that the introduction of the two indoles occurs in two distinct steps, a radical process and a Friedel–Crafts alkylation reaction. Coumarin and flavonoid derivatives are very valuable precursors in drug synthesis. In 2015, Ge et al. developed the regioselective and atom

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• correct structure, ending two decades of controversies. Triacetonamine is an important chemical feedstock, used for drug synthesis and the production of flavors, and nowadays also has electronic applications. The Guareschi synthesis of triacetonamine was industrialized by Schering in connection with the

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

• provided an easy access to the synthesis of complex bioactive molecules with multiple point diversity incorporating up to eight components in one-pot [8]. The pharmaceutical industry has witnessed a considerable surge in drug synthesis via multicomponent strategies [9][10][11], including the synthesis of

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• that the reaction is broad in scope. Remarkably, C–S bonds and spiro compounds have been constructed simultaneously in this approach, which are promising for drug synthesis. Substrate 46 comprises both indole and alkynone groups, leading to light-promoted intramolecular electron transfer in order to

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• oxygen and their mechanisms. Adapted from [67]. First scaled up ascaridole preparation from α-terpinene. Antimalarial drug synthesis using an endoperoxidation approach. Photooxygenation of colchicine. Synthesis of (−)-pinocarvone from abundant (+)-α-pinene. Seeberger’s semi-synthesis of artemisinin

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• degree of structural diversity that should be of interest in drug synthesis or material science. The versatility of alkoxyallenes [11][12][13][14][15][16][17][18][19][20][65][66] as easily available C3 building blocks is key for this prosperousness. Discovery of the LANCA three-component reaction. The

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• synthesis of very specific drug molecules are used to explore and evaluate the design approach for building a single synthesis platform that can help produce all of those drug molecules, each having a very different synthesis route. How do we use it for drug synthesis? The proposed options of a unified

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• Josef Jansa Ramona Schmidt Ashenafi Damtew Mamuye Laura Castoldi Alexander Roller Vittorio Pace Wolfgang Holzer Division of Drug Synthesis, Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria Research Institute for

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• Taofeng Shao Zhiming Gong Tianyi Su Wei Hao Chao Che Laboratory of Chemical Genomics, Engineering Laboratory for Chiral Drug Synthesis, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China 10.3762/bjoc.13.82 Abstract Diversity-oriented

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• Bo Yang Chuanye Tao Taofeng Shao Jianxian Gong Chao Che Laboratory of Chemical Genomics, Engineering Laboratory for Chiral Drug Synthesis, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China 10.3762/bjoc.12.145 Abstract A novel three

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• or pyrimidines with subsequent aromatization of the heterocyclic ring. We also noticed that the final composition of these markers was dependent on the reaction conditions during the drug synthesis [24]. In order to unequivocally confirm the presence of newly identified markers in the reaction

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• 1-amino-2,4-dibromoanthraquinone directly from 1-aminoanthraquinone in excellent yields (94–100%) and high purities. The synthesized brominated AQs are valuable precursors for the preparation of AQ drugs and dyes. Keywords: anthraquinone; bromaminic acid; drug synthesis; dyes; intermediates

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• a convenient one-pot process for the preparation of structurally diverse cyclic imides starting from readily available primary amines and cyclic anhydrides using APS–DMSO as an efficient and novel dehydrating reagent and its application to a drug synthesis. The scope of the developed protocol was

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• tools in organic synthesis. Among numerous applications they are applied as chiral ligands [1], as catalysts for various asymmetric transformations [2], and as building blocks for alkaloid and pharmaceutical drug synthesis [3][4]. The increasing number of applications leads to a growing interest in the

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• Barbara Palka Angela Di Capua Maurizio Anzini Gyte Vilkauskaite Algirdas Sackus Wolfgang Holzer Division of Drug Synthesis, Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria Department of Biotechnology, Chemistry and

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• acid derivative; radical alkylation; Introduction γ-Lactams exist in many natural products and biologically active compounds and are one of the most important classes of compounds for drug discovery [1][2][3]. Substituted γ-lactams, in particular, have potential application in drug synthesis, but the

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• commonly used routes in drug synthesis. Different heterocyclic structures will be introduced and discussed in individual subsections. In Table 1 a summary of these structures is shown. We believe that this article will give an enlightening overview of both the classical heterocycle syntheses as well as

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis. Keywords: biologically active compounds; boronic acid; copper; N-arylation; palladium; Introduction Palladium- and