Synthesis of new β-amino acids and novel β-peptides, and structural investigations

246 Pages·2008·13.28 MB·English

ETH Library
Synthesis of new β-amino acids
and novel β-peptides, and
structural investigations
Doctoral Thesis
Author(s):
Lelais, Gérald
Publication date:
2004
Permanent link:
https://doi.org/10.3929/ethz-a-004715484
Rights / license:
In Copyright - Non-Commercial Use Permitted
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Diss. ETH No. 15429
Synthesis of New ß-Amino Acids and Novel
ß-Peptides, and Structural Investigations
A dissertation submitted to the
EIDGENÖSSISCHE TECHNISCHE HOCHSCHULE
ZÜRICH
for the degree of
Doctor of Natural Sciences
Presented by
Gerald PatrickJoseph Jean Louis LELAIS
Dipl. Chem. ETH
born May 7,1976
from Iseo (TI)
Accepted on the recommendation of
Prof. Dr. Dieter Seebach, examiner
Prof. Dr. Peter H. Seeberger, co-examiner
Zürich, 2004

For Rajjaella
ana ray parents

I am deeply indebted to my
'Doktorvater'
Prof. Dr. Dieter Seebach
for his encouraging guidance, his intellectual support and
for the granted freedom throughout my dissertation

Aknowledgements
This work would not have been possible without the help of many people that I
would like to thank.
In particular I am deeply grateful to my colleagues Dr. Francesco Rossi, Dr. Marino
Campo, Dr. Peter Micuch, and Dr. Delphine Josien-Lejebvre that with their experience
were of great help for the success of this work.
I am much obliged to my two diploma students Sascha Kopp and Daniel Egli for their
devotion during their Master Thesis, as well as to Marine Guillot, Antonia Stepan, and
Christian Defieber for their contribution during the advanced organic laboratory
courses (OCPII).
I would also like to thank Arno Wortmann and Prof. Dr. Renato Zenobi for the MS-
studies of the zinc-complexing peptides, and for the interesting discussions. At the
same time, I appreciate the collaborative work of Raveendra Mathad and Prof. Bernhard
Jaun, which led to the NMR-solution structure of the peptide 76.
Sincere thanks go to Dr. Klaus Piontek and Dr. Thomas Choinowski for their willingness
and help in performing the crystallisation trials of the zinc-complexingpeptides.
I am grateful to Dr. Bernd Schweizer for determining all X-ray crystal structures
presented in this work.
I am thankful to Yogesh R. Mahajan for his help in setting up the protocols for the
automated peptide synthesis of the ß-peptide 80.
I would like to thankAlbert K. Beck for his helpfulness, for his suggestions for solving
practical difficulties, for the proofreading of the experimental part of this work, and
for his friendship. I thank Silvia Sigrist, Daniela Kalbermater and Valérie Sebbaâ for their
friendliness and their support in different administrative tasks.
I am thankful to Prof. Dr. Peter H. Seeberger for agreeing to be the co-examiner.
I would like to thank the analytical section of the department of organic chemistry
for their precious assistance: Prof. Dr. Bernhard Jaun, Brigitte Brandenberger, Philipp
Zumbrunnen (NMR); Dr. Walter Amrein, RolfHäfliger, Oswald Greter, Oliver Scheidegger
(MS); Michael Schneider, Dieter Manser (EA). In addition, I am grateful to Dr. Engelbert
Zass (literature search) and Joseph Meienberger (Bibliothek); as well as to all the
permanent employees of the laboratory (Schalter, Werkstatt, Hausdienst) for
providing me efficient infrastructures.
For critical reading of this thesis and for his suggestions in improving it, I am deeply
grateful to Dr. David Hook. Additionally, my warmest thank goes to my fiancée
Raffaella for her help in writing the "Riassunto".
For the great time I had in the multitude of labs I worked in (D62, F306 and E306), I
would like to thank my lab-mates Magnus Riiping ("mach doch eine Kilo Säule...ist
besser"), Christoph Gaul ("allet aber würklich allet fü de..."), Kevin Volken ("grande
Lugano"), Dr. Francesco Rossi ("indovina un po'...chachacha"), Dr. Delphine Josien-
Lefebvre ("Do you have a problem?"), Dr. David Hook ("I'm so busy"), Thierry
Kimmerlin (J'en ai marre"), Dr. Marino Campo, Dr. Kenji Namoto and Dr. Radovan
Sebesta. In addition, I am grateful to all the members of the Seebach group for the
pleasant atmosphere during these years.
I could not forget all the members of the glorious LocDoc-Team Peter Manini, Andrea
Piatesi, Romain Siegrist, Fraser Hof, Stefan Sahli, Tobias Welti, Daniel Latassa, David
Carcache e William Pomerantz for the brilliant performances achieved during the
numerous uni-hockey championships.
And, lastbut not least: vorrei ringraziare in modo particolare Raffaella, i miei genitori
e i miei fratelli per i loro incoraggiamenti ed il continuo supporto durante tutti questi
anni di studio.
Parts of this Thesis have been published:
Gerald Lelais and Dieter Seebach
Synthesis and CD Spectra of ß2-(3-Aza-peptides)
Peptides: The Wave of the Future, Proceedings of the Second International and the
Seventeenth American Peptide Symposium, Eds. M. Lebl, R. A. Houghten, San
Diego, 2001, pp. 581.
Magnus Rueping, Jürg V. Schreiber, Gerald Lelais, BernhardJaun and Dieter Seebach
Mixed ß2/ß3-Hexapeptides and ß3/ß2-Nonapeptides Folding to (P)-Helices with
Alternating Twelve- and Ten-Membered Hydrogen-Bonded Rings
Helv. Chim. Acta 2002, 85, 2577.
Dieter Seebach, Laurent Schaeffer, François Gessier, Pascal Bindschädler, Corinna
Jäger, Delphine Josien, Sascha Kopp, Gerald Lelais, Yogesh R. Mahajan, Peter
Micuch, Radovan Sebesta and Bernd W. Schweizer
Enantioselective Preparation of 2-Aminomethyl-Carboxylic Acid Derivatives.
Solving the ß2-Amino Acid-Problem with the Chiral Auxiliary DIOZ.
Preliminary Communication
Helv. Chim. Acta 2003, 86,1852.
Francesco Rossi, Gerald Lelais and Dieter Seebach
Zn2+-Complexation by a ß-Peptidic Helix and Hairpin Containing ß3hCys and
ß3hHis Building Blocks Evidence from CD Measurements
-
Preliminary Communication
Helv. Chim. Acta 2003, 86, 2653.
Gerald Lelais and Dieter Seebach
Synthesis, CD Spectra and Enzymatic Cleavage Investigation of ß2-3-Aza-Peptides
Helv. Chim. Acta 2003, 86, 4152.
Gerald Lelais, Marino A. Campo, Sascha Kopp and Dieter Seebach
Enantioselective Preparation of ß2-Amino Acids with Aspartate, Glutamate,
Asparagine and Glutamine Side Chains
Helv. Chim. Acta 2004, in press.