Lysine-Based Amphiphiles with Pyrrole, Furan and Thiophene Linkers
Year: 2026
Type: article
Abstract: The development of efficient cationic amphiphiles remains an important area in the design of nonviral systems for nucleic acid delivery. In this study, we report the synthesis of three lysine-containing lipid-like amphiphiles incorporating pyrrole, furan, and thiophene as five-membered heterocyclic linkers. The compounds share a common molecular scaffold comprising two heterocyclic linkers with a lysine-derived cationic moiety and two tetradecyl chains, while differing in the five-membered heterocyclic core. The target amphiphiles were synthesized using a four-step synthetic approach involving Cu(I)-catalyzed azide–alkyne cycloaddition, followed by Boc deprotection and anion exchange to afford compounds 6a–c as tetrahydrochloride salts. The final compounds were isolated in a 39–50% range over the final two steps. Their structures were confirmed by NMR spectroscopy and high-resolution mass spectrometry. Additional multinuclear two-dimensional NMR experiments were used to support the structural assignment of compound 6a. These amphiphiles provide new structures for further investigation of their physicochemical properties, self-assembly, nucleic acid complexation, and potential application in nonviral nucleic acid delivery.
Source: Molbank
DOI: 10.3390/m2243
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $603
OpenAlex ID: W7221944258