Synthesis And Characterization Of Piperazine Derivatives And Salidroside Analogues, And The Study On The Biological Activity

Piperazine belonges to six-membered heterocyclic compounds, is an important drug synthesis intermediates, the drugs containing piperazine show a variety of biological activitives, such as:anti-bacterial, anti-cancer, anti-pain, anti-hypertension etc. The pharmacological effects of piperazine derivatives are highly depended on the substitutes in of piperazine rings, so more and more researchers focused on drug research and development of piperazine derivatives. Rhodiola is a valuable medicinal plant, salidroside belonged to glycoside compound is one of the effective components of Rhodiola rosea extract. The study shows salidroside has anti-virus, anti-tumor, protect cardiovascular system and can improve immune system and many other kinds of pharmacological effects.In order to study the piperazine derivatives and salidroside analogues in depth, this dissertation adopts the piecing together principle, coupling with better bioactive compounds and then do some appropriate modification. We also do some tests with a view to get new drug candidates with better biological activity.There are three parts in this dissertation:First part:Briefly introduce the research progress of piperazine and Rhodiola. Describe the application of piperazine derivatives in the field of medicine and the pharmacological effects of Rhodiola, and development prospects of piperazine derivatives and salidroside analogues.Second part:Design, synthesis and characterization of piperazine derivatives and salidroside analogues.55derivatives were synthesized through exploring the conditions of synthesizing, separating and purifying,37kinds of the compounds have not been reported, details are as followed:1. Protecting N-1position of the piperazine, and then combination of protected amino acid and N-4position of the piperazine, removing N-1position protecting groups of the piperazine and coupling with the other protected amino acid. After remove the protecting groups we get thirteen piperazine derivatives.2. Combination of protected N-1position of the piperazine and protected amino acid, and then remove the protecting groups. We get six piperazine derivatives.3. Combination of protected N-1position of the piperazine and p-fluorobenzoic acid, and then remove N-1position protecting groups of the piperazine and coupling with protected amino acid. After remove the protecting groups we get eight piperazine derivatives.4. Doing some structure modification of four pentacyclic triterpenoid compounds and then introducing connecting fragment succinic acid at C-3or C-2position, After coupling with protected N-1position of the piperazine, and remove the protecting groups. Finally we get eight piperazine derivatives.5. Combination of tyrosol analogues and tetra-O-acetyl-a-D-glucopyranosyl bromide, and then remove the acetyl group and the benzyl protecting groups. Finally we get five salidroside analogues.The piperazine derivatives and salidroside analogues were characterized by IR and1H NMR.Third part:The amino acid conjugates of piperazine and the pentacyclic triterpenoid derivatives of piperazine were studied by the antibacterial activity, and the pentacyclic triterpenoid derivatives of piperazine were studied by the antitumor activity.