TY - GEN AU - Pollák, Patrik AU - Garádi, Zsófia AU - Volk, Balázs AU - Dancsó, András AU - Simig, Gyula AU - Milen, Mátyás TI - Studies on the total syntheses of β‑carboline alkaloids orthoscuticellines A and B PY - 2024 UR - https://m2.mtmt.hu/api/publication/35218538 ID - 35218538 LA - English DB - MTMT ER - TY - GEN AU - Borsos, Ákos AU - Hámori, Csaba AU - Szilágyi, Emőke AU - Spaits, András AU - Farkas, Ferenc AU - Százdi, László AU - Kátainé Fadgyas, Katalin AU - Volk, Balázs AU - Szilágyi, Botond TI - Digitális megoldások alkalmazása az eljárásfejlesztés, illetve méretnövelés során : egy példa az iparból PY - 2024 UR - https://m2.mtmt.hu/api/publication/35054151 ID - 35054151 LA - Hungarian DB - MTMT ER - TY - GEN AU - Volk, Balázs TI - Egy tucat év, két tucat új gyűrűrendszer PY - 2024 UR - https://m2.mtmt.hu/api/publication/35053918 ID - 35053918 LA - Hungarian DB - MTMT ER - TY - GEN AU - Pollák, Patrik AU - Garádi, Zsófia AU - Volk, Balázs AU - Dancsó, András AU - Simig, Gyula AU - Milen, Mátyás TI - Ortoszkuticellin A és B alkaloidok szintézisének vizsgálata PY - 2024 UR - https://m2.mtmt.hu/api/publication/35051016 ID - 35051016 LA - Hungarian DB - MTMT ER - TY - GEN AU - Pollák, Patrik AU - Garádi, Zsófia AU - Volk, Balázs AU - Dancsó, András AU - Simig, Gyula AU - Milen, Mátyás TI - Studies on the total syntheses of β carboline alkaloids orthoscuticellines A and B PY - 2024 UR - https://m2.mtmt.hu/api/publication/34882898 ID - 34882898 LA - English DB - MTMT ER - TY - JOUR AU - Ábrányi-Balogh, Péter AU - Molnárné Samu, Erika AU - Pánczél, János K. AU - Benkő, Zoltán AU - Simig, Gyula AU - Volk, Balázs TI - Computational Studies on the Diastereospecific Lithium Variant of Oppenauer Oxidation of a Tofisopam Intermediate JF - JOURNAL OF ORGANIC CHEMISTRY J2 - J ORG CHEM VL - 89 PY - 2024 IS - 8 SP - 5298 EP - 5303 PG - 6 SN - 0022-3263 DO - 10.1021/acs.joc.3c02660 UR - https://m2.mtmt.hu/api/publication/34778896 ID - 34778896 N1 - Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, H-1111, Hungary National Laboratory for Drug Research and Development, Magyar tudósok krt. 2, Budapest, H-1117, Hungary Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., Budapest, H-1475, Hungary Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szt. Gellért tér 4, Budapest, H-1111, Hungary Export Date: 12 April 2024 CODEN: JOCEA Correspondence Address: Ábrányi-Balogh, P.; Medicinal Chemistry Research Group, Magyar tudósok krt. 2, Hungary; email: abranyi-balogh.peter@ttk.hu Correspondence Address: Volk, B.; Directorate of Drug Substance Development, Hungary; email: volk.balazs@egis.hu LA - English DB - MTMT ER - TY - JOUR AU - Semghouli, Anas AU - Drahos, László AU - Volk, Balázs AU - Kiss, Loránd TI - Selective Transformation of 1,3‐Cyclooctadiene into Novel Functionalized Azaheterocycles, β‐Amino Esters, and Lactams by Means of Ring‐Rearrangement Metathesis JF - EUROPEAN JOURNAL OF ORGANIC CHEMISTRY J2 - EUR J ORG CHEM VL - 27 PY - 2024 IS - 18 SN - 1434-193X DO - 10.1002/ejoc.202400170 UR - https://m2.mtmt.hu/api/publication/34719334 ID - 34719334 AB - Diversity‐oriented synthesis of some novel functionalized azaheterocyclic β‐amino esters with multiple chiral centers from 1,3‐cyclooctadiene‐based β‐amino acids through a stereocontrolled synthetic route has been accomplished. The strategy was based on the creation of some novel unsaturated N‐protected cyclic β‐amino esters from 1,3‐cyclooctadiene. Products were subjected to ring‐opening metathesis (ROM) followed by selective ring‐closing metathesis (RCM). A comparative investigation on the selectivity, regarding the catalysts, yields, conversions, and substrate directing effect on ring‐rearrangement metathesis (RRM) transformation has been accomplished. Importantly, the procedure used in this synthetic process does not affect the configuration of the chiral centers. The pathway takes place across conservation of the configurations of the stereocenters; therefore, the architectural skeleton of the starting cyclooctene‐based β‐amino acids predetermined the structure of the new azaheterocyclic systems. LA - English DB - MTMT ER - TY - JOUR AU - Orosz, Álmos AU - Szilágyi, Emőke AU - Spaits, András AU - Borsos, Ákos AU - Farkas, Ferenc AU - Markovits, Imre AU - Százdi, László AU - Volk, Balázs AU - Kátainé Fadgyas, Katalin AU - Szilágyi, Botond TI - Dynamic Modeling and Optimal Design Space Determination of Pharmaceutical Crystallization Processes: Realizing the Synergy between Off-the-Shelf Laboratory and Industrial Scale Data JF - INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH J2 - IND ENG CHEM RES VL - 63 PY - 2024 IS - 9 SP - 4068 EP - 4082 PG - 15 SN - 0888-5885 DO - 10.1021/acs.iecr.3c03954 UR - https://m2.mtmt.hu/api/publication/34681008 ID - 34681008 N1 - Department of Chemical and Environmental Process Engineering, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., Budapest, H-1111, Hungary Egis Pharmaceuticals Plc, P.O. Box 100 10, Budapest, H-1475, Hungary Export Date: 8 March 2024 CODEN: IECRE Correspondence Address: Szilágyi, B.; Department of Chemical and Environmental Process Engineering, Műegyetem rkp. 3., Hungary; email: szilagyi.botond@vbk.bme.hu Funding details: Hungarian Scientific Research Fund, OTKA, FK-138475 Funding text 1: This research was supported by the Hungarian National Scientific Research Fund (OTKA) grant FK-138475. The financial support from Egis Pharmaceuticals PLC is also gratefully acknowledged. AB - Well-designed and operated pharmaceutical crystallization can enhance the key features of the active pharmaceutical ingredients, which can be taken to the next level by a model-based design. Model development not only requires computer implementation, kinetic identification, and advanced programming skills but also a suitable number of information-rich experiments. Numerous products have been crystallized for a long time, with many related laboratory-scale experiments and plant-scale manufacturing data accumulated from past developments and productions. The question arises: can these historical data be utilized to build process models, which can be used subsequently to optimize processes? We aim to demonstrate in this study that this approach can be feasible. To illustrate this, we used the data of two commercial crystallization production campaigns, totaling 16 industrial crystallizations, and six laboratory experiments, four of which were formerly performed for different purposes. Our tailored PBM involves primary and secondary nucleation, crystal growth, and dissolution and can simultaneously reproduce laboratory- and plant-scale dynamics. Despite relying on nontargeted experiments and measuring/sampling strategy, the estimated parameters were accurate, with an average deviation between the nominal values and 95% confidence interval bonds of 16.1%. The model was employed to construct an optimal design space (DS) for a temperature cycling operation involving, as a constraint, 2, 3, and 4 cycles: the goal was to define a temperature domain with minimal batch time and heating/cooling energy demand that respects the constraints on the product PSD and heating/cooling rates. The problem was solved as a constrained robust optimization, where discrete temperature stamps and corresponding time stamps were optimized. The optimal operation halved the current batch time. The optimized temperature profile was validated on a laboratory scale for two particle size specifications. More expansive DS (1 vs 0.5 h random temperature variation allowed around the nominal temperature profile) was observed to translate to longer batch times (30 vs 25 h) and deeper temperature cycles of 40 vs 20 °C, reflecting a trade-off between nominal performance and robustness. The optimal laboratory-scale operation was validated successfully by repeated experiments. © 2024 American Chemical Society. LA - English DB - MTMT ER - TY - JOUR AU - Pollák, Patrik AU - Garádi, Zsófia AU - Volk, Balázs AU - Dancsó, András AU - Simig, Gyula AU - Milen, Mátyás TI - Studies on the total syntheses of β ‑carboline alkaloids orthoscuticellines A and B JF - NATURAL PRODUCT RESEARCH J2 - NAT PROD RES PY - 2024 PG - 9 SN - 1478-6419 DO - 10.1080/14786419.2024.2306600 UR - https://m2.mtmt.hu/api/publication/34532109 ID - 34532109 N1 - Directorate of Drug Substance Development, Egis Pharmaceuticals PLC, Budapest, Hungary Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary Export Date: 3 April 2024 CODEN: NPRAA Correspondence Address: Milen, M.; Directorate of Drug Substance Development, Hungary; email: milen.matyas@egis.hu Published online on: 25 Jan 2024 LA - English DB - MTMT ER - TY - JOUR AU - Poszávácz, László AU - Porcs-Makkay, Márta AU - Halász, Judit AU - Mórász, Tamás AU - Nagy, Tamás AU - Kátainé Fadgyas, Katalin AU - Simig, Gyula AU - Volk, Balázs TI - Points of Interest in the Chemistry of the Levomepromazine Drug Substance: Recycling of Undesired Enantiomer, Identification of New Phenothiazine Dimers, Synthesis of a Pharmacopeial Impurity, and an Unexpected Rearrangement JF - ORGANIC PROCESS RESEARCH & DEVELOPMENT J2 - ORG PROCESS RES DEV VL - 28 PY - 2024 IS - 1 SP - 281 EP - 292 PG - 12 SN - 1083-6160 DO - 10.1021/acs.oprd.3c00368 UR - https://m2.mtmt.hu/api/publication/34483970 ID - 34483970 LA - English DB - MTMT ER -