Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• pharmaceutical ingredient edaravone (52, Table 2, entry 10). In this study, a self-optimizing flow reactor was used to run the optimization of seven continuous variables

• ). A particularly noteworthy development is the application of TSEMO for the optimization of synthetic routes composed of two and more successive reaction steps or telescoped reactions [83][84][85]. Sagmeister et al. [83] reported the optimization of a two-step telescoped synthesis of the active

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• compounds leads to the formation of pyrazoles 24 in a one-pot process (Scheme 6) [54]. This versatile method enables the introduction of various functional groups at position 1 of the pyrazole ring. In addition, it can also be employed in synthesizing celecoxib, an active pharmaceutical ingredient. Starting

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• siliceous rock against pyrite [2][3]. Mechanochemistry comes with intrinsic advantages associated with the lack of solvent use during reaction, thus largely reducing the generation of waste [4] even in active pharmaceutical ingredient synthesis [5]. Yet mechanochemistry also allows the production of novel

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• is provided and the reaction demonstrates reasonable regioselectivity (6.5:1). The synthesis of 15c, a precursor to an active pharmaceutical ingredient (API), by the authors demonstrates how this method is immediately useful in the synthesis of biologically active molecules. Although the authors

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• active pharmaceutical ingredient (API). This further establishes oxidative dehydrogenation as an impactful strategy in the repertoire of organic synthesis (Scheme 40). The next example demonstrates the process of oxidative dehydrogenation in the synthesis of bioactive natural products. Accordingly, Stahl

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• active pharmaceutical ingredient (API) entrapped in a polymeric scaffold. The results pointed out that the motion of a small drug molecule drastically changes from subdiffusive to slightly superdiffusive regimes depending on the cyclodextrin to CL molar ratio, and hence on the CDNS polymeric structure

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• compound or active pharmaceutical ingredient (API) synthesis in this industry. There has been some research in the last decade demonstrating the preparation of cocrystals by hot melt extrusion (HME) and liquid assisted extrusion. This work has been essentially conducted by Amgen, preparing cocrystals

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• preparation of an active pharmaceutical ingredient (API), the anticonvulsant drug ethotoin 7 [9] (marketed as Peganone®, Scheme 1). We describe herein the impact of the addition of variable amounts of PEG, PEG chain length and end terminal groups, for the preparation of diverse 3,5-disubstituted hydantoins

Release of β-galactosidase from poloxamine/α-cyclodextrin hydrogels

• César A. Estévez,
• José Ramón Isasi,
• Eneko Larrañeta and
• Itziar Vélaz

Beilstein J. Org. Chem. 2014, 10, 3127–3135, doi:10.3762/bjoc.10.330

• , first order, and Hopfenberg. Korsmeyer developed a simple formula to describe the release of the active pharmaceutical ingredient (API) from a polymeric system. They found that this model is acceptable up to an amount of 60% of API released. The exponent of the power law indicates the release mechanism

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• anaesthesia. Keywords: active pharmaceutical ingredient; binding constant; cyclodextrin; derivatization; gas chromatography; sevoflurane; substitution pattern; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-1,4-linked glucose units. Those CDs consisting of 6, 7, and 8 glucose units are called α

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• of the active pharmaceutical ingredient (API) (analysis will be included on future publications). We hypothesized that by both reducing the cost of goods via chemistry changes and reducing the unit operations the most significant cost reduction could be achieved. Herein, we demonstrate a proof of

• improvements, we suggest that a commercial version of this process must address how to achieve long-term stability at the higher concentrations. Creating a chemical process for an active pharmaceutical ingredient is a careful integration of chemical and regulatory challenges. While from an academic standpoint

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• (CNC·HCl, 1, Figure 1) is the first active pharmaceutical ingredient (API) approved by the USFDA for the treatment of secondary hyperparathyroidism. It is sold under the trade names of Sensipar® in USA and Mimpara® in Europe. Hyperparathyroidism (HPT) is a condition characterized by the over-secretion of

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

Identification and synthesis of impurities formed during sertindole preparation

• I. V. Sunil Kumar,
• G. S. R. Anjaneyulu and
• V. Hima Bindu

Beilstein J. Org. Chem. 2011, 7, 29–33, doi:10.3762/bjoc.7.5

• ) was <0.05% [10]. Conclusion For the better understanding of the synthetic pathway of an active pharmaceutical ingredient (API) it is necessary to identify all the impurities formed/anticipated. In this regard we have synthesized and characterized different potential process-related impurities of