Synthesis of azetidines, γ-lactams, fused furan bispyrrolidines and 2-pyrazolines: towards medical application

Download Statistics

Downloads

Downloads per month over past year

Hama Salih, Mariwan Abdulla (2016). Synthesis of azetidines, γ-lactams, fused furan bispyrrolidines and 2-pyrazolines: towards medical application. University of Birmingham. Ph.D.

Preview

Hama_Salih16PhD.pdf
PDF - Redacted Version
Download (10MB)

Abstract

Azetidines are important class of heterocyclic organic compounds in drug discovery and natural product synthesis. Several natural products and pharmaceuticals are containing azetidine precursors such as, penaresidin and Azelnidipine. Iodine mediated cyclisation of homoallylamines were found to furnish iodoazetidines at 20 °C and further reaction with amine nucelophiles afforded aminoazetidines in high yields. The cyclisation of various homoallylamines which different substitution patterns using molecular iodine to furnish new classes of compounds with interesting biological applications were studied. The iodocyclisation of 3-methyl substituted homoallylamine were found to deliver γ-lactam compound in moderate yield as a mixture of diastereoisomers, the reaction conditions were optimised, and the separation into single diastereoisomers and modification in to pyrrolidine ring were investigated. The tricyclic furan bispyrrolidines were obtained in relatively low yields when 3-phenyl substituted homoallylamines were cyclised using the same strategy. The cyclisation of homoallylhydrazines to deliver pyrazoline compounds in high yield was studied in detail. Finally, the biological activity of some of the synthesised compounds were investigated in zebrafish embryo developmental assays and showed intriguing biological responses. Some of the synthesised compounds were sent to Syngenta and Lilly Company for further investigation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):