Modular and chromatography-free synthesis of natural linear polyamines

Polyamines are essential for mammalian cell growth and proliferation and contribute to DNA replication, protein synthesis, and other critical biological processes. Herein, we report a concise and efficient route, for synthesising polyamines from commercially available diamines and amino acid derivatives via simple purification. This strategy employs EDC-mediated condensation, Red-Al reduction, and carbamate protection and deprotection reactions, enabling a short synthetic sequence without the need for column chromatography. Across all steps, only a single liquid-liquid extraction is required, with all other operations limited to solvent removal, precipitation, and final purification by recrystallisation. This modular sequence was uniformly applied across different chain lengths, affording natural polyamines such as spermine and thermospermine, as well as rarer higher polyamines including caldopentamine and caldohexamine. This method provides convenient access to biologically relevant polyamines, and may facilitate future biochemical and pharmaceutical research.