Synthesis And Biological Activity Of Solanesyl Triamines

The thesis includes four parts: a brief review on solanesyl derivatives and polyamines;the synthesis and structural modification of solanesyl triamine and the biological activity ofN-(4- solanesylpiperazine-1-yl)alkyl polyamine derivatives; the preliminary synthesis ofasymmetric linear triamine skeletons; a review and research on the synthetic technique ofCoenzyme Q₀. Part 1 Introduction A brief introduction is made on the background and prospect of both solanesylderivatives and solanesylamines, and the recent study on linear polyamine derivatives.Part 2 Study on Synthesis, Interaction with DNA and Bioactivity of N-(4-Solanesylpiperazine-1-yl)alkyl Amines and Their Derivatives2.1 Synthesis of N -(4-Solanesylpiperazine-1-yl)alkyl Amines and Their Amides Solanesol, acting as a stating material, undergoes several steps to affordsolanesylpiperazine. And the key intermediate 4 was prepared through Gabrial method :solanesylpiperazine was reacted with N-bromoalkylphthalimide affording 3, which wasrefluxed with hydrazine hydrate in alcohol to give 4. Then compounds 4 was treated with thecorresponding acids in presence of coupling agent DCC to give the target compounds 8, 9, 10.2.2 Synthesis of N -(4-Solanesylpiperazine-1-yl)alkyl Amine Derivatives The intermediates 4 was reacted with corresponding aldehydes to give the related Schiffbases, and the Schiff bases were reduced with NaBH4 without separation to achieve thetarget compounds 15,16,17.2.3 Biological Activity and Interaction with DNA All the target compounds, together with the three commercial drugs (5- Fluorouracil,Biphenylacetic Acid, Naproxen), were tested in vitro for their inhibition on four kinds ofhuman cancer cells: KB, A-549, MDA and Bel-7402 by Drug Scanning Center in ChineseMedical Science Academy. The Ultraviolet and fluorescence spectra of several targetcompounds demonstrate that the interaction between investigated compound and DNAresembles that of nonionic surfactant without the intercalary effect as lipid polyaminesacting on DNA.Part 3 Preliminary Synthesis of Asymmetric Linear Triamine Skeletons N-(3-bromopropyl)phthalimide was reacted with butylamine to give compound 19, the2 amine 19 was N-protected to form 20 using excess di-tert-dicarbonate, Boc₂O. Then 20was refluxed with hydrazine hydrate in alcohol to give amine 21. Further reactions wereperformed by repeated process through which the mono-Boc protected asymmetric lineartriamine 23 was prepared.Part 4 Synthesis of 2,3-Dimethoxy-5-Methyl-1,4-Benzoquinone The reaction was investigated with the method of orthogonal design, and 49% yield ofQ0 was stably realized through repeated experiments, and the optimal condition is that:n( 3,4,5-trimethoxytoluene): n(H2O2)=0.28:1, reacting temperature 40℃, reacting time 2h,m(catalyst): m (3,4,5-trimethoxytoluene)=0.5:100 which will be easy to be operated...