The synthesis and chemistry of [2.2]paracyclophane amino acid derivatives : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Chemistry at Massey University, Manawatū, New Zealand
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Date
2020
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Massey University
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Abstract
Due to the ever-growing requirement for chiral compounds, new conditions for stereoselective synthesis are in constant development. Asymmetric organocatalysis is well-studied, with peptide catalysts popular due to their modular and highlyfunctionalisable nature. One such example of their utility is in the Michael reaction, a well-studied carbon-carbon bond forming reaction.
[2.2]Paracyclophane is an aromatic industrial precursor compound with remarkable structural and electronic properties. Its conformational bulk and rigidity make it an attractive target for integration into sterically-hindered unnatural amino acids for incorporation into peptides that may be effective organocatalysts.
An updated route to 4-amino-13-[2.2]paracyclophane-carboxylic acid (Pca) was developed and optimised. The synthetic route comprises four steps with an overall yield of 50%. This compares with previous routes which had yields between 7 and 48% for 6 - 7 steps. Peptide coupling conditions for the poorly-reactive Pca were developed with some success; including devising a route for direct synthesis of a glycine residue on Pca’s aniline. Four new Pca-containing peptides were described. The above work sets the stage for development of interesting new planar chiral peptide compounds with diverse chemistry.
Three Pca-containing peptides were studied as asymmetric organocatalysts in Michael addition between trans-β-nitrostyrene and hexanal and were compared to proline, a known catalyst for this reaction. These tests were performed to probe the relationship between relative conformation between the carboxylic acid and amine moieties of the catalyst, and the catalyst’s stereoselectivity. The Pca-containing catalysts showed an interesting trend to reversal of the prevailing syn product configuration.
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Peptides, Cyclophanes, Amino acids, Synthesis, Catalysis, Chirality