Synthesis of Functional Modules - NCCR MSE

Synthesis of Functional Modules

We are creating and exploring nano-reaction chambers as catalysts for substrate and product selective reactions. Such functional modules will be the basis for the construction of molecular factories.

The successful creation of a molecular factory relies on the delicate interplay of all its subcomponents. To avoid undesired cross-reactivity, the subcomponents have to display high substrate selectivity. One way to achieve substrate selectivity is the utilization of nano-reaction chambers, which due to their limited cavity volume only convert molecules of suitable size.

Beside substrate selectivity, nano-reaction chambers also provide product selectivity. Due to the restricted environment inside the catalyst, the substrate conformation is influenced, which can lead to different products than in a regular solution experiment. Additionally, weak interactions between the host and the guest molecule can influence the reaction pathway.

As a first step towards molecular factories, we will investigate multi-catalyst tandem reactions utilizing two or more nano-reaction chambers. Natural enzymes will be combined with man-made nano-reaction chambers to obtain novel reactivity.


H. Chen, T. Li, N. Sakai, C. Besnard, L. Guénée, M. Pupier, J. Viger-Gravel, K. TiefenbacherS. Matile “Decoded fingerprints of hyperresponsive, expanding product space: polyether cascade cyclizations as tools to elucidate supramolecular catalysis“ Chemical Science 2022. [DOI]
T. Li, F. Huck, G. Piccini, K. Tiefenbacher “Mimicry of the proton wire mechanism of enzymes inside a supramolecular capsule enables β-selective O-glycosylations“ Nat. Chem. 2022. [DOI]
L. Syntrivanis, K. Tiefenbacher “Catalysis Inside the Hexameric Resorcinarene Capsule: Toward Addressing Current Challenges in Synthetic Organic Chemistry“ Supramolecular Catalysis 2022. [DOI]
S. J. Nemat, K. Tiefenbacher “Thioderivatives of Resorcin[4]arene and Pyrogallol[4]arene: Are Thiols Tolerated in the Self-Assembly Process?“ Org. Lett. 2021. [DOI]
X. Hao, T. Li, H. Chen, A. Gini, X. Zhang, S. Rosset, C. Mazet, K. TiefenbacherS. Matile “Bioinspired Ether Cyclizations within a π-Basic Capsule Compared to Autocatalysis on π-Acidic Surfaces and Pnictogen-Bonding Catalysts“ Chem. Eur. J. 2021. [DOI]
S. J. Nemat, D. Van den Eynden, L. Deblock, M. Heilmann, J. M. Köster, M. Parvizian, K. TiefenbacherJ. De Roo “Resorcin[4]Arene-Based Multidentate Phosphate Ligands with Superior Binding Affinity for Nanocrystal Surfaces“ Chem. Commun. 2021. [DOI]
M. Heilmann, M. Knezevic, G. Piccini, K. Tiefenbacher “Understanding the Binding Properties of Phosphorylated Glycoluril-Derived Molecular Tweezers and Selective Nanomolar Binding of Natural Polyamines in Aqueous Solution“ Org. Biomol. Chem. 2021. [DOI]
S. Merget, L. Catti, S. Zev, D. T. Major, N. Trapp, K. Tiefenbacher “Concentration-dependent Self-assembly of an Unusually Large Hexameric Hydrogen-bonded Molecular Cage“ Chem. Eur. J. 2020. [DOI]
I. Némethová, L. Syntrivanis, K. Tiefenbacher “Molecular Capsule Catalysis: Ready to Address Current Challenges in Synthetic Organic Chemistry?“ Chimia 2020. [DOI]
S. J. Nemat, H. Jędrzejewska, A. Prescimone, A. Szumna, K. Tiefenbacher “Catechol[4]arene: The Missing Chiral Member of the Calix[4]arene Family“ Org. Lett. 2020. [DOI]
M. Knezevic, M. Heilmann, G. Piccini, K. Tiefenbacher “Overriding Intrinsic Reactivity in Aliphatic C–H Oxidation: Preferential C3/C4 Oxidation of Aliphatic Ammonium Substrates“ Angew. Chem. Int. Ed. 2020. [DOI]
F. R. Bissegger, M. Neuburger, K. Tiefenbacher “Scope of the Direct Trimerisation to C3-Symmetric Cyclotribenzylene Derivatives“ Supramol. Chem. 2020. [DOI]
L. Syntrivanis, I. Némethová, D. Schmid, S. Levi, A. Prescimone, F. Bissegger, D. T. Major, K. Tiefenbacher “Four-Step Access to the Sesquiterpene Natural Product Presilphiperfolan-1β-ol and Unnatural Derivatives via Supramolecular Catalysis“ J. Am. Chem. Soc. 2020. [DOI]
S. Merget, L. Catti, G. Piccini, K. Tiefenbacher “Requirements for Terpene Cyclizations inside the Supramolecular Resorcinarene Capsule: Bound Water and Its Protonation Determine the Catalytic Activity“ J. Am. Chem. Soc. 2020. [DOI]
M. Heilmann, K. Tiefenbacher “A Modular Phosphorylated Glycoluril-Derived Molecular Tweezer for Potent Binding of Aliphatic Diamines“ Chem. Eur. J. 2019. [DOI]
Q. Zhang, K. Tiefenbacher “Sesquiterpene Cyclizations inside the Hexameric Resorcinarene Capsule: Total Synthesis of δ-Selinene and Mechanistic Studies“ Angew. Chem. Int. Ed. 2019. [DOI]
Q. Zhang, L. Catti, L. Syntrivanis, K. Tiefenbacher “En route to terpene natural products utilizing supramolecular cyclase mimetics“ Nat. Prod. Rep. 2019. [DOI]
J. M. Köster, D. Häussinger, K. Tiefenbacher “Activation of Primary and Secondary Benzylic and Tertiary Alkyl (sp3)C-F Bonds Inside a Self-Assembled Molecular Container“ Front. Chem. 2019. [DOI]
Q. Zhang, L. Catti, K. Tiefenbacher “Catalysis inside the Hexameric Resorcinarene Capsule“ Acc. Chem. Res. 2018. [DOI]
Q. Zhang, J. Rinkel, B. Goldfuss, J. S. Dickschat, K. Tiefenbacher “Sesquiterpene cyclizations catalysed inside the resorcinarene capsule and application in the short synthesis of isolongifolene and isolongifolenone“ Nat. Catal. 2018. [DOI]
J. M. Köster, K. Tiefenbacher “Elucidating the Importance of Hydrochloric Acid as a Cocatalyst for Resorcinarene‐Capsule‐Catalyzed Reactions“ ChemCatChem 2018. [DOI]
T. Braeuer, Q. Zhang, K. Tiefenbacher “Iminium Catalysis inside a Self-Assembled Supramolecular Capsule: Scope and Mechanistic Studies“ J. Am. Chem. Soc. 2017. [DOI]
Q. Zhang, L. Catti, J. Pleiss, K. Tiefenbacher “Terpene Cyclizations inside a Supramolecular Catalyst: Leaving Group-Controlled Product Selectivity and Mechanistic Studies“ J. Am. Chem. Soc. 2017. [DOI]
C. H. Pollok, Q. Zhang, K. Tiefenbacher, C. Merten “Chirality induction from a chiral guest to the hydrogen bonding network of its hexameric resorcinarene host capsule“ ChemPhysChem 2017. [DOI]
L. Catti, A. Pöthig, K. Tiefenbacher “Host-Catalyzed Cyclodehydration–Rearrangement Cascade Reaction of Unsaturated Tertiary Alcohols“ Adv. Synth. Catal. 2017, 359:1331-38. [DOI]
Q. Zhang, L. Catti, V. R. I. Kaila, K. Tiefenbacher “To catalyze or not to catalyze: elucidation of the subtle differences between the hexameric capsules of pyrogallolarene and resorcinarene“ Chem. Sci. 2017. [DOI]