Synthesis And Biological Activity Of "Polyamine-Drug" Conjugates

In this thesis, two series of homospermidine derivatives were designed and synthesized, and their bioactivity was also studied. Twenty six target compounds including twenty three unreported compounds were prepared, and the structure of those compounds was confirmed by ¹HNMR, ¹³CNMR, ESI-MS and elemental analysis. Finally, we studied the interaction of some target compounds with Herring Sperm DNA, and their anticancer activity using MTT method.Part 1 IntroductionA brief introduction of the background, recent study and prospect about polyamine derivatives was made in this part, also including our idea about this thesis.Part 2 Study on the Synthesis of polyamine Derivatives 1. Synthesis of homospermidine derivatives N1-(4-phthalimide)butyl-N1,N4-di-tert-butoxycarbonylbutane-1,4-diamine (4) was prepared by the tandem reactions of substitution and protection using N-tert-butoxy carbonylbutane-1,4-diamine and 4-bromobutylphthalimide as the starting materials. Then (4) was treated with hydrazine hydrate to remove its phthalimide group to give N1-aminobuty l-N1,N4-di-tert-butoxycarbonylbutane-1,4-diamine (5). (5) was condensed with aryldehydes or arylketones, then the crude product was reduced with NaBH4. After purifying, the reduced product was deprotected to provide the target compounds 21～35 with a different yield in these three steps. Structures of those compounds were confirmed by ¹³CNMR, ¹HNMR, ESI-MS and Elemental Analysis.2. Synthesis of N-Piperazine-Homospermidine DerivativesUsing the similar way preparing compound (5), we synthesized compound (46). The intermediate (46) reacted with corresponding aldehydes to give the related Schiff bases, and the Schiff bases were reduced with NaBH₄. After purifying, the reduced product was...