University of Groningen
Exploitation of macrocyclic chemical space by multicomponent reaction (MCR) and their
applications in medicinal chemistry
Abdelraheem, Eman Mahmoud Mohamed
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2018
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Abdelraheem, E. M. M. (2018). Exploitation of macrocyclic chemical space by multicomponent reaction (MCR) and their applications in medicinal chemistry. Rijksuniversiteit Groningen.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
APPENDIX
About the author
Publications
Conferences
About the author
ABOUT THE AUTHOR:
Eman Abdelraheem was born in Sohag, Egypt. She obtained her B. Sc. degree in
Chemistry and did her M. Sc. in Organic Chemistry under the guidance of Prof. Ahmed K. El-Shafei at Sohag University, Egypt. During her master’s degree, she worked on the project ‘Synthesis of some New Spiro and Fused Heterocyclic Compounds’. She is an assistant lecturer at Chemistry Department, Faculty of Science, Sohag University. Currently, she is pursuing her Ph. D. under the supervision of Prof. Alexander Dömling at Drug Design Department, University of Groningen, Netherlands. Her research interests include drug Discovery, multicomponent reactions (MCR) and application of MCR toward the synthesis of artificial macrocycles and its application as potent p53-MDM2 inhibitors. She is the author of more than 20 scientific articles and reviews, and she joined for more than 10 international conferences. For her Ph. D. studies, she was awarded an Egyptian Ph. D. Scholarship.
Publications
273
PUBLICATIONS
Abdelraheem, E. M. M.; Shaabani, S. & Dömling, A. (2018). “Artificial
Macrocycles”; Synlett, 29, A-P. DOI: 10.1055/s-0036-1591975
Abdelraheem, E. M. M.; Khaksar, S.; Kurpiewska, K.; Kalinowska-Tłuścik, J.;
Shaabani, S.& Dömling, A. (2018). “Two Step Macrocycle Synthesis by Classical Ugi Reaction” Journal of Organic Chemistry, 83 (3), 1441–1447. DOI: 10.1021/acs.joc.7b02984
Abdelraheem, E. M. M.; Khaksar, S. & Dömling, A. (2018). “Concise Synthesis
of Macrocycles by multicomponent Reactions ( MCRs)”; Synthesis, 50, 1027– 1038. DOI: 10.1055/s-0036-1590946
Abdelraheem, E. M. M.; Madhavachary, R.; Rossetti, A.; Kurpiewska, K.;
Kalinowska-Tłuścik, J.; Shaabani, S. & Dömling, A. (2017). “Ugi Multicomponent Reaction Based Synthesis of Medium-Sized Rings”; Organic letters,19 (22), 6176–6179. DOI: 10.1021/acs.orglett.7b03094
Abdelraheem, E. M. M.; de Haan, M. P.; Patil, P.; Kurpiewska, K.;
Kalinowska-Tłuścik, J.; Shaabani, S.& Dömling, A. (2017). “Concise Synthesis of Tetrazole Macrocycle”; Organic letters, 19, 5078-5081. DOI: 10.1021/acs.orglett.7b02319 Madhavachary, R.;+ Abdelraheem, E. M. M.;+ Rossetti, A.; Twarda-Clapa, A.;
Musielak, B.; Kurpiewska, K.; Kalinowska-Tłuścik, J.; Holak T. A. & Dömling, A. (2017). “Two-Step Synthesis of Complex ArtificialMacrocyclic Compounds”. Angew.Chem. Int. Ed., 56,10725-10729. DOI: 10.1002/anie.201704426;
[+]Shared the first coauthorship
El-Remaily, Mahmoud A. A.; Elhady, O. M. & Abdelraheem, E. M. M. (2017). “Synthesis and Antimicrobial Screening of Fused Heterocyclic Pyridines”; Journal of Heterocyclic Chemistry, 54, 871. DOI:10.1002/jhet.2648
Abdelraheem, E. M. M.; Kurpiewska, K.; Kalinowska-Tłuścik, J. & Dömling, A.
(2016). “Artificial Macrocycles by Ugi Reaction and Passerini Ring Closure”; Journal of Organic Chemistry, 81(19), 8789- 8795. DOI: 10.1021/acs.joc.6b01430
El-Remaily, Mahmoud A. A.; Elhady, O. M.; Abo Zaid, H. S. & Abdelraheem, E.
Publications
Pyridopyrimidine Derivatives”; Journal of Organic Chemistry, 53, 1304. DOI: 10.1002/jhet.2420
Mague, J. T.; Mohamed, S. K.; Akkurt, M.; Abdelraheem, E. M.
M.& Albayati, M. R. (2016).
“1-((E)-{2-4-(2-{(1E)-[(carbamothioylamino)-imino]methyl}phenoxy)butoxy]benzylidene}amino)thiourea Dimethyl sulfoxide disolvate”; IUCrData, 1, x160946. DOI: 10.1107/S2414314616009469
Mohamed, S. K.; Younes, S. H. H.; Abdelraheem, E. M. M., Horton, P. N.; Akkurt, M.& Glidewell, C. (2016). “Triclinic and monoclinic polymorphs of meso-(E,E)-1,1'-[1,2-bis(4-chlorophenyl)ethane-1,2-diyl]bis (phenyldiazene): the high-yield synthesis of an unexpected product, concomitant polymorphism and configurational disorder"; Acta Crystallography, C72, 57-62. DOI: org/10.1107/S2053229615023578
Abdelraheem, E. M. M.; Camacho, C. J. & Dömling, A. (2015). “Focusing on
shared subpockets-new developments in fragment-based drug discovery”; Expert
Opinion on Drug Discovery, 10(11), 1179-87. DOI:
10.1517/17460441.2015.1080684
Liao, G. P.;+ Abdelraheem, E. M. M.;+ Neochoritis, C. G.; Kurpiewska, K.; Kalinowska-Tłuścik, J.; McGowan, D. C. & Dömling, A. (2015). “Versatile Multicomponent Reaction Macrocycle Synthesis Using α-Isocyano-ω-carboxylic Acids”; Organic letters, 17(20), 4980-3. DOI:10.1021/acs.orglett.5b02419; [+] Shared the first coauthorship
Younes, Sabry H. H. & Abdelraheem, E. M. M. (2015). “One-Pot Synthesis and Biological Study of New Barbituric Acid Derivatives Using PTC Technique”; International Journal of Chemical and Pharmaceutical Analysis (IJCPA), 2(3): 152-160. DOI: http:/doi.org/10.21276/ijcpa
Publications
275 Mohamed, S. K.; Younes, S. H. H.; Abdelraheem, E. M. M.; Mague, J. T.;
Akkurt, M. & Glidewell, C. (2015). “The interplay of solvation, molecular conformation and supramolecular assembly in 1,1'-({[(ethane-1,2-diyl)dioxy](1,2-phenylene)}bis(methanylylidene))bis(thiosemicarbazide) and its N,N-dimethyl-formamide disolvate”; Acta Crystallography, C71, 959-964. DOI: 10.1107/S2053229615018744
Akkurt, M.; Mohamed, S. K.; Horton, P. N.; Abdelraheem, E. M.
M. & Albayati, M. R. (2013). “2,2'-[Ethane-1,2- diylbis(oxy)]dibenzaldehyde”
Acta Crystallography, E69, o1260. DOI:10.1107/S1600536813019156
Mohamed, S. K.; Soliman, A. M.; Abdelraheem, E. M. M.; Saeed, S. & Wong, W.-T. (2012). “2-Amino-6 (dimethylamino)pyridine-3,5-dicarbonitrile”; Acta Crystallography, E68, o1532. DOI:10.1107/S1600536812017278
Horton, P. N.; Mohamed, S. K.; Soliman, A. M.; Abdelraheem, E. M. M. & Akkurt, M. (2012). “2-(Piperidin-1-yl)-6-(1H-pyrrol-1-yl)-pyridine-3,5-dicarbonitrile”; Acta Crystallography, E68, o938. DOI: 10.1107/S1600536812008586
Horton, P. N.; Mohamed, S. K.; Soliman, A. M.; Abdelraheem, E. M. M. & Akkurt, M. (2012). “2-(Morpholin-4-yl)-6-(1H-pyrrol-1-yl)-pyridine-3,5-dicarbonitrile”; Acta Crystallography, E68, o885- o886. DOI:10.1107/S160053681200815X
Publications
Others reporting about my work
Contributor(s): Timothy M. Swager, Cassandra A. Zentner
Madhavachary, R.;+ Abdelraheem, E. M. M.;+ et al. (2017). “Two Steps to Loops”; Synfacts, 13(10): 1028. DOI: 10.1055/s-0036-1591245:
Significance: The use of macrocycles as antagonists in medicinal chemistry is a growing
field. Typically, macrocycles are synthesized by using multistep peptide synthesis followed by additional functionalization reactions. Such methods are time-consuming and lack chemical diversity. In this work, the authors present an effective, general two-step reaction that can be used to construct a library of artificial macrocycles.
Comment: The authors developed a simple, yet robust, two-step process towards complex
macrocycles, based on the Ugi reaction. The broad scope of the reaction incorporates a wide variety of side chains (amino acids, sugars, non-natural) and loop sizes (8–19-membered rings). The reaction is tolerant to side-chain functional groups, such as hydroxyl groups and esters. The library of 36 molecules synthesized represents a concrete starting point to artificial macrocycles. With increasing complexity of the ketones/aldehydes and isocyanides, this universal method could efficiently produce effective antagonists.
Conferences
277
CONFERENCES
255th ACS National Meeting, 2018, 18-22nd March 2018, New Orleans, LA, US. (Oral & Poster presentation).
CHAINS 2017, 5-7th December 2017, Veldhoven, The Netherlands. (Poster presentation).
ELF Annual Chemistry Learnings and Achievements Meeting 2017, 6-7th November 2017, Janssen Campus Beerse, Belgium (Oral & Poster presentation). CHAINS 2016, 6-8th December 2016, Veldhoven, The Netherlands. (Poster
presentation).
CHAINS 2015, 1-2nd December 2015, Veldhoven, The Netherlands. (Oral presentation).
The Medicinal Chemistry & Bioanalysis meeting (MCB 2015), August 28th 2015, Groningen, The Netherlands (Lecture).
The Medicinal Chemistry & Bioanalysis symposium (MCB 2014), 25-26th August 2014, Groningen, The Netherlands. (Poster presentation).
11th International Conference on Chemistry and Its Role in Development 2013, 11-15th March 2013, Mansoura-Sharm El Sheikh, Egypt. (Poster presentation). International Conference of Young Chemists (ICYC 2012), 8-10th April 2012,
Amman, Jordan. (Poster presentation).
3rd International conference of biological and Environmental sciences (ICBES
2012), 20-24th March 2012, Mansoura-Hurgada, Egypt. (Poster presentation). The 11th International Chemistry conference and Exhibition in Africa (11 ICCA
Acknowledgements
Acknowledgements
Here it ends! A little over four years my PhD has come to the end. One of the most difficult things for me, is to find words to express my gratitude to so many people who helped me so much, either in work or in life. I would like to express my deepest gratitude to all of them. First and foremost, I offer my earnest gratitude to my supervisor and promotor Prof. Alexander Dömling. Alex, your support, motivation, guidance and unflinching encouragements were instrumental towards the fulfillment of my thesis. I will remember you as a funny person, friendly and easy going attitude toward your students. I will always remember your unlimited enthusiasm about new experiments or ideas and your writing on the blackboard in my office. I will remember when you call me “lady of macrocycles” each time we publish an article. I will not forget the first time when I gave an oral presentation in CHAINS conference. You came to my office to tell me I did registration for you and the lady of macrocycles Eman able to do it. Alex, thank you very much for giving me an opportunity to work with you, to learn your own unique art, multicompoenet reactions (MCRs) and to grow in your lab as an independent researcher. I will remember the nice week, which we shared ACS meeting in the US, the interesting lectures which we gave and which we had. The delicious seafood that we had together. Really, I learned a lot from you. I am grateful, for everything!!!
I would like to thank my co-promotor, Dr. Matthew Groves, Thank you for the nice discussions, your suggestions during the PhD evaluation each year and more specially during my thesis submission. I will remember you as a friendly and a kind person that greets me every day with a smile- full.
I would like to acknowledge the members of the reading committee: Prof. Frank Dekker from the University of Groningen, Prof. dr. Christopher Hulme from the Arizona University and Prof. Valentine Nenajdenko from Moscow State University for their time and efforts to evaluate and approve this thesis, for the nice comments and their encouragement to keep up the good work.
Next, I have to be grateful to my collaborators from Poland. Prof. Dr. Tad A. Holak and Dr. Aleksandra Twarda-Clapa, Thank you for your great support during the screening of my biologically active compounds in your lab. Dr. Katarzyna Kurpiewska and Dr. Justyna Kalinowska-Tłuścik, thank you for measuring the huge single crystal X-ray structures from this thesis. You always answered my questions so patiently and played a very important role to confirm the difficult structures in my projects.
Acknowledgements
279 Our steadfast problem solver secretary Jolanda for being there always, to help me with administrative issues and all the questions I had regarding sending parcels and conferences. Thank you, Jolanda!
Our lab manager, André, your work as a technician in our group is invaluable and you have my respect for all the things you arrange for the lab. Many thanks for translating my thesis summary in Dutch.
Tryfonas, my PhD paranymph, I can not find words to express my thankful to you. You are always there to help everyone. I will not forget at the beginning of my Ph.D. that you guide me in the lab. You have been a trusted co-worker in the lab and office mate. I always wonder about your helping and kind nature with everyone. I wish you an excellent future. I’m so very glad that I met you. Above all, you always every morning greet me with a smiling face “Good morning Eman”, I think you did not forget to say it during more than four years.
I want to express my warmest feelings to Dinos (my PhD paranymph) and Patil (my office mate), both of you are excellent chemists but in two different ways. I liked to work with both of you. Besides the chemistry which I win from both of you. From Dinos, I learned how can I think in all the small details of my reaction with a cub of coffee before I go to the lab. From Patil, I learned how can I take very fast action even if I am under stress. Thanks guys!!
Chary, thank you very much for sharing me the biggest macrocycle project which we did together. Thanks for sharing ideas, experience and discussions. You are a very patient person and the best thing that you were very relaxed during the discussions. Really I enjoyed a lot during our work. Best wishes for your future.
I would like to pass my sincere thanks to Santosh for all the nice conversations and discussions (scientific and non-scientific). Best wishes for your future.
Many thanks to our postdoc and my co-author Shabnam, it is a nice experience to work with you and I really enjoyed this opportunity. Also, I am glad to work with you on ongoing projects. My best wishes are always with you.
Thanks to my Ph.D. colleagues, Ajay, Ting, and Edwin, for discussions and information about credit courses and project progress. Ajay, I will always remember our long discussion about project progress and thesis plans. I will remember even after you left, you always answer my questions.
During the four years, I have met a lot of people, Our lab mates, Vishwanatha, Natalia, Yuanze, Markella, Qian, Jingyao, Fandi, Robin, Roberto, Michel, and Bupendra. I am grateful for all the nice memories and for the nice working environment.
Moreover, I would like to thank the visiting scientists from all over the world: Silvia, Arianna, Paola, Samat, Maxx, Evo, Leni, Ewa, Fanny, Keas, Harmen, Perry, and Erico.
Acknowledgements
Thanks to our biology lab colleagues Sergey, Atlio, Ameena, Alaa, Fernando,and Kai. I would like to thank the people from the group of Prof. Dekker, and first-year labmates, Marilena, Nick, Hannah, and Martijn. I want to express my warmest feelings to Marilena. You became a very good colleague. You have a very open, sincere, thoughtful, and generous personality, and this is what I like about you. I am glad that we have met. I will not forget our talking and laughing. I wish you all the best in your career in Greece.
I also supervised students, my master and bachelor students, Samir, Max, Deka, Ellen, Juliana, Jan ledeboer, Maryam, Michel, and Imogen, It was nice learning and fun experience with you guys. I have enjoyed teaching you my own skills in chemistry and win from you some computer skills. I wish you all the best in your future careers.
My great thanks to Prof. Shaaban K. Mohamed, Manchester University, UK, for helping me to get my scholarship and for supporting me during my PhD trip.
I would like to thank our friend Dr. Saleh Mohamed, for your helping us when we arrived at Netherland. Many thanks to you for your suggestions and comments during the design of the cover of my thesis.
My family: parents, brothers and sisters and their kids, thank you very much for your unconditional love, affection, and support during this long trip. My special thanks to my mum for her constant support and motivation, and without which it would not have been possible to attain this level of education.
I would also like to extend my sincere gratitude to my sisters Heba, Basma, and Nora. You are amazing personalities. I am very thankful for your motivation and reminders. Even though I was far away from all of you, but it never feels that ways when we have chat. My kids, my lovely daughter Lekaa and my strong son Ahmed, you are always the sun of my life. I would like to let you know that, in the past four years, I had many frustrating moments and lost my motivation several times. But every time when I came home and saw you two were there waiting for me, I was recovered and I could keep going. You may not know it but you have largely contributed to this work, as both of you have witnessed this journey and you are the driving force behind me to finish this thesis. I promise both of you that I will not talk a lot about chemistry experiments at home, I will try to keep your advice that “Lab. for the chemistry and home for the fun with my kids”. Thank you.
