Synthesis of Fluorinated Amino Acids and Their Derivatives in Flow

208 Pages·2017·8.19 MB·English

by  Stella Vukelic

Synthesis of Fluorinated
Amino Acids and Their
Derivatives in Flow

Inaugural-Dissertation
to obtain the academic degree
Doctor rerum naturalium (Dr. rer. nat)

submitted to the Department of Biology, Chemistry and Pharmacy
of Freie Universität Berlin

by
Stella Vukelić
From Zagreb, Croatia
July, 2016
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This work was performed between October 2012 and April 2016 under the guidance of Prof. Dr. Beate
Koksch and Prof. Dr. Peter H. Seeberger in the Department of Biomolecular Systems, Max Planck
Institute of Colloids and Interfaces Potsdam and the Institute of Chemistry and Biochemistry, Freie
Universität Berlin.

I hereby declare that this PhD thesis was prepared autonomously. Content, quotes or images
previously published by third parties are indicated by referring to the original work.
The work presented in this dissertation resulted in the following publications:
• Stella Vukelić, Kerry Gilmore, Beate Koksch, Peter H. Seeberger, “A Sustainable Semi-
Continuous Flow Synthesis of Hydantoins”, Eur. J. Of Chem. A, 2016, DOI:
10.1002/chem.201602609.
• Stella Vukelić, Johann Moschner, Susanne Huhmann, Rita Fernandes, Allison Ann Berger,
Beate Koksch, “Synthesis of side-chain fluorinated amino acids and their effect on biophysical
properties of peptides and proteins in “Modern Synthetic Routes and Reactivity of Fluorinated
Compounds”, H. Groult, F. Leroux & A. Tressaud, Eds., Elsevier, in press.
• Stella Vukelić, Dmitry B. Ushakov, Kerry Gilmore, Beate Koksch, Peter H. Seeberger, “Flow
Synthesis of Fluorinated Amino Acids”, Eur. J. Org. Chem. 2015, 14, 3036-3039.

1st reviewer: Prof. Dr. Beate Koksch
2nd reviewer: Prof. Dr. Peter H. Seeberger

Date of oral defense: November 18th 2016
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To my grandad
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Acknowledgements
First, I wish to express my gratitude to Professor Beate Koksch for giving me the opportunity to do my
PhD research as a part of her group. I am thankful for the trust to develop and pursue my own ideas
and for the opportunity to attend international conferences.
Further, I want to thank Professor Peter H. Seeberger for hosting me at the Biomolecular Systems and
for giving me the opportunity to work as a part of the Flow subgroup.
I am grateful to Professor Tyler D. McQuade for accepting and welcoming me to the Flow group at
the very start and Dr. Kerry Gilmore for the guidance, support and understanding from the beginning
until the end of my PhD studies.
Thank you Dr. Camille A. Correia, Dr. Allison A. Berger, Dr. Diego Ghislieri, Dr. Anna Chentsova,
Rita Fernandes and Matt Plutschack for proof reading the thesis and Dr. Bart Pieber for help with
translation of my summary to german.
I am grateful that I had the chance to have worked with Dr. Dmitry B. Ushakov, Dr. Camille A.
Correia, Dr. Diego Ghislieri and Matt Plutschack. Dmitry B., thank you for the guidance, patience and
support. Camille and Diego, thank you for the endless chemistry and life advice and for the constant
encouragement and support. Matt, thank you for all the help and advice, writing the thesis without
your help would be a struggle. I learned a lot from you and without you guys, lab days would not be
nearly as fun.
I was also lucky to have met and spent time with other wonderful people from the Seeberger group,
both past and the present members who made my graduate life more fun.
Thank you Rita, Jason and Elsa for the friendship and love you sent from FU.
I would like to acknowledge the staff. Thank you Olaf Niermeyer and Fabian Klautzsch for your help
with NMR and HRMS. Thank you Günther Hasselof for the help with building our flow equipment.
Thank you Dorothee Böhme for all the help with administration.
Finally, I would like to thank my croatian support team, my friends and my family. I am always indebt
to these people. I would have never made it without their love and encouragement. Thank you for not
giving up on me, even when I gave up myself.
The true sign of intelligence
is not knowledge but imagination
Albert Einstein
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List of Publications
Scientific Publications and Book Chapters
 Stella Vukelić, Kerry Gilmore, Beate Koksch, Peter H. Seeberger, “A Sustainable Semi-
Continuous Flow Synthesis of Hydantoins”, Eur. J. Of Chem. A, 2016, DOI:
10.1002/chem.201602609.

 Stella Vukelić, Johann Moschner, Susanne Huhmann, Rita Fernandes, Allison Ann Berger,
Beate Koksch, “Synthesis of side-chain fluorinated amino acids and their effect on biophysical
properties of peptides and proteins in “Modern Synthetic Routes and Reactivity of Fluorinated
Compounds”, H. Groult, F. Leroux & A. Tressaud, Eds.
Elsevier, in press.

 Stella Vukelić, Dmitry B. Ushakov, Kerry Gilmore, Beate Koksch, Peter H. Seeberger, “Flow
Synthesis of Fluorinated Amino Acids”, Eur. J. Org. Chem. 2015, 14, 3036-3039.
o Featured in an interview by ChemistryViews: http://www.chemistryviews.org/details/ezine/
7956531/FlowSynthesis_of_Fluorinated_Amino_Acids.html

 Kerry Gilmore, Stella Vukelić, D. Tyler McQuade, Beate Koksch, Peter H. Seeberger,
“Continuous Reductions and Reductive Aminations Using Solid NaBH ”, Org. Process Res. Dev.
4
2014, 18, 1771-1776.
o Featured in C&E News (cen.acs.org) 24.11.2014 “Sodium Borohydride Goes With The
Flow”, November 24, 2014 (92(47)).

 Jyotirmoy Maity, Ulla I. M. Gerling, Stella Vukelić, Andreas Schäfer, Beate Koksch,
“Proline-glutamate chimera's side chain conformation directs the type of β-hairpin structure”, Amino
Acids 2014, 46, 177-186.

Scientific Conferences and Symposia
18th European Symposium on Fluorine Chemistry, Kiew; Ukraine (2016), Synthesis of Hydantoins in
Flow, poster presentation.
JungChemikerForum Berlin, Berlin, Germany, (2016), Synthesis of Hydantoins in Flow, oral
presentation.
Gordon Conference, Organic Reactions and Processes, Lewiston, USA (2015), Flow Synthesis of
Fluorinated Amino Acids, poster presentation.
Tetrahedron Conference, Berlin, Germany, (2015), Flow Synthesis of Fluorinated Amino Acids, poster
presentation.
JungChemikerForum Berlin, Berlin, Germany, (2015), Flow Synthesis of Fluorinated Amino Acids,
oral presentation.