Foldamers and Macrocycles Based on Formamidoxime Subunits

Abstract

The objective of this thesis is the study of the control of the shape of formamidine motifs and application to folding open-ended structures and more elaborate macrocycles.

The multi-step synthesis of macrocycles M1 and M2, which are analogs of 18-crown ether-6, have been successfully achieved. Macrocycles M1 and M2 have been fully characterized. The study of the crystal structures of M1 and M2 gave interesting information about their packing and molecular recognition properties.

Moreover, analysis of some by-products formed in macrocyclizations gave intriguing results. The existence of a four-pyridine-unit interlocked catenane which was isolated from the synthesis of M1 has been confirmed by MS-MS. A surprisingly large 54-membered macrocycle “Maxi-M2” was isolated from the synthetic crude product of M2 and confirmed by X-ray crystallography.

Driven by the desire to understand the formation of catenane and “Maxi-M2”, a systematic study of the corresponding condensation reaction was performed. The E isomers derived from N-acyl-N’-substituted formamidoximes were, for the first time, reported and isolated. The protons can facilitate E to Z isomerization. The best conditions to selectively generate either the E or Z isomers have been fully studied and applied to the synthesis.

The unexpected formation of the E isomers may promote polymerization and limit the yield improvement of macrocyclization. Therefore, a new synthetic method for the target macrocycle M2 was investigated, trying to avoid the formation of E isomers and thus cyclize more efficiently.