Non-standard methodology in organic synthesis : mechanochemistry with macrocycles and sporopollenin

Abdulwahaab, Bassim Habeeb

Abstract

Glyoxal-bridged bisaminal tetraazamacrocyclic derivatives of 1,4,7,10 tetraazacyclododecane (cyclen) and 1,4,8,11- tetraazacyclotetradecane (cyclam) can be N-functionalized to incorporate coordinating groups or for conjugation to biomolecules. Herein, an improved N-functionalisation methodology is presented using mechanochemistry which reduces reaction times in comparison with conventional synthetic routes. A range of six alkyl halides were reacted with cyclen and cyclam bisaminal derivatives in various ratios to form mono- and bis-functionalized quaternary ammonium salts. CB-TE2A, a commonly used chelator in positron emission tomography medical imaging, has been synthesized using non-conventional synthetic methodologies (grinding and microwave heating) with intermediates characterized by 2D NMR and single crystal XRD. The overall synthesis time of CB-TE2A from cyclam could be shortened to 5 days from the 35 days required for the conventional synthesis.
Sporopollenin exines are made from a natural biopolymer with unusually resistant materials. Spores extracted from the Date Palm (Phoenix dactylifera L.), were treated with ammonia to produce amide groups on the surface with a loading of (0.642 mmol. gm-1 ± 0.04), which can be converted a primary amine by reduction with lithium aluminum hydride (0.6 mmol. gm-1 ± 0.05 ). The attendance of the primary amine and precursor amide groups were determined by elemental combustion analysis (CHN), ICP-OES, Fourier transform infrared spectroscopy and solid-state NMR. The primary amine group methyl iodide for salt formation, and phenyl isothiocyanate and benzene sulfonyl chloride for nucleophilic addition and substitution respectively
Lycopodium clavatum (L C) was extracted from fresh pollen and spores, and then mechanochemistry was used to make a basic form by attachment of 1,6-hexane diamine with a loading of (1.7mmol. gm-1 ± 0.04) this was followed by attachment of a macrocyclic chelator DOTA (which has a high affinity for gallium(III)). The sporopollenin derivatives were radiolabeled with 68Ga isotope at room temperature (yield 55%) and 90oC (92% RCY). The stability was tested in competition with transferrin, PBS (95%) and simulated gastric fluid (94%).

Citation

Abdulwahaab, B. H. Non-standard methodology in organic synthesis : mechanochemistry with macrocycles and sporopollenin. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4224065

• Thesis Type: Thesis
• Deposit Date: Mar 24, 2022
• Publicly Available Date: Feb 24, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4224065
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Aug 1, 2016