Foldamer-templated catalysis of macrocycle formation
Zebediah C Girvin1, Mary Katherine Andrews1, Xinyu Liu1
1Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
Science (New York, N.Y.)
|December 21, 2019
Summary
Researchers developed a new bioinspired method for synthesizing macrocycles using a catalytic peptide foldamer. This approach facilitates ring closure via carbon-carbon bond formation, overcoming a key challenge in organic chemistry.
Area of Science:
- Synthetic Organic Chemistry
- Catalysis
- Supramolecular Chemistry
Background:
- Macrocycles (≥12 atoms) are vital in medicine, fragrances, and sensing.
- Efficient macrocycle synthesis is challenging due to entropic costs and competing intermolecular reactions.
Purpose of the Study:
- To present a novel bioinspired strategy for macrocycle formation via carbon-carbon bond formation.
- To utilize a catalytic α/β-peptide foldamer for templating ring-closing reactions.
Main Methods:
- Employing an α/β-peptide foldamer catalyst with a specific helical conformation.
- The foldamer features a catalytic primary amine-secondary amine diad for promoting reactions.
- Utilizing aldol reactions for macrocycle formation.
Main Results:
- Successfully synthesized macrocycles with ring sizes ranging from 14 to 22 atoms.
- Demonstrated the utility of the method in synthesizing the natural product robustol.
- The catalytic foldamer effectively templates the ring-closing process.
Conclusions:
- The presented bioinspired strategy offers an efficient route to macrocycle synthesis.
- Catalytic foldamers can overcome challenges in large-ring formation.
- This method holds promise for accessing complex macrocyclic structures.
Related Concept Videos
01:16Cycloaddition Reactions: MO Requirements for Thermal Activation
4.1K
Thermal cycloadditions are reactions where the source of activation energy needed to initiate the reaction is provided in the form of heat. A typical example of a thermally-allowed cycloaddition is the Diels–Alder reaction, which is a [4 + 2] cycloaddition. In contrast, a [2 + 2] cycloaddition is thermally forbidden.
4.1K
01:16Cycloaddition Reactions: Overview
3.3K
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
3.3K
01:13Olefin Metathesis Polymerization: Overview
2.5K
Recently, the development of olefin metathesis polymerization advanced the field of polymer synthesis. Simply put, the reorganization of substituents on their double bonds between two olefins in the presence of a catalyst is known as the olefin metathesis reaction. The use of metathesis reaction for polymer synthesis is called olefin metathesis polymerization.
Ruthenium-based Grubbs catalyst is the most commonly used catalyst for olefin metathesis polymerization. Grubbs catalyst consists of a...
Ruthenium-based Grubbs catalyst is the most commonly used catalyst for olefin metathesis polymerization. Grubbs catalyst consists of a...
2.5K
01:12Cycloaddition Reactions: MO Requirements for Photochemical Activation
2.5K
Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
2.5K
01:16Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)
3.1K
Ring-opening metathesis polymerization or ROMP involves strained cycloalkenes as starting materials. The mechanism of ROMP proceeds by reacting cycloalkene with Grubbs catalyst to give metallacyclobutane intermediate which undergoes a ring-opening reaction to form new carbene. The new carbene reacts with another molecule of cycloalkene. Repetition of these steps leads to the formation of an unsaturated open-chain polymer product. All these steps are reversible, however, relieving the ring...
3.1K
01:27Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
2.7K
Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).
2.7K