C <sub> 60 </ Sub> Anti-hiv Activity Studies With The Formyl Dehydroabietylamine Derivatives 1,3 - Dipolar Cycloaddition Reaction And Its Water-soluble Product

Fullerene and its derivatives were widely applied in chemistry, biology,material and medicine for their particular three-dimensional structures. Fullerene[60], the most representative compound, has particular efficacy andbioactivity in anti-HIV, antibacterial, antitumor, inhibition of enzymatic activity,antioxidation, neuroprotective and so on. Dehydroabietylamine which is the maincomponent of disproportionated rosin amine, with a three-ring phenanthrenestructure, has sterilization and other biological activities. Therefore, supposed a newmolecule which is synthesized from C₆₀and dehydroabietylamine, and it would bea valuable topic to study the bioactivity of this new molecule.In this paper, dehydroabietylamine, as one of the reactants, was added toglyoxal with anhydrous ethanol as solvent. The condensation reaction occurred atreflux temperature, a novel Schiff base (2a) derived from glyoxal anddehydroabietylamine was synthesized. N-methyl-2-dehydroabietyliminomethyl-3,4-fullerene pyrrolidine (3a) was synthesized by reaction of compound2a, sarcosineand C₆₀, through the1,3-dipolar cycloaddition reaction reacted at reflux temperaturewith toluene as solvent. All the products was characterized by IR,1H NMR,13CNMR, ESI-MS and MALDI-TOF-MS.Dehydroabietylamine as raw material, acetic anhydride as N-protection reagent,7-carbonyl acetyl dehydroabietylamine (1b) was synthesized through by oxidation.The VHA reaction occurred at reflux temperature, compound1b and DMF/POCl3asreactants,1,2-dichloroethane as solvent. Different from expectations,13-chloro-2,3-di(N,N-dimethylamino)-1-formyl-11-isopropyl-5a,8a-dimethyl-5a,6,7,8,8a,13c-hexahydrophenanthrene[5a,13c-f:13c,13a-g]-5,5a,13a,3c-tetrahydroindolizine (2b)was synthesized. N-methyl-3,4-fullerene pyrrolidine (3b) was synthesized byreaction of compound2b, sarcosine and C₆₀, through the1,3-dipolar cycloadditionreaction reacted at reflux temperature with toluene as solvent. The final product andintermediates was characterized by IR,1H NMR,13C NMR, ESI-MS, HRMS,MALDI-TOF-MS and elemental analysis.Based on fulleropyrrolidine derivatives which were synthesized in front, thenovel fullerenol pyrrolidine derivatives were synthesized by reaction offulleropyrrolidine derivatives and H2O2, in toluene/water mixed solution at refluxtemperature, with TBAH as the catalyst. The target compounds were characterizedby IR, elemental analysis and TGA. The everage molecular formula of compound4a(The hydroxylated product of compound3a) was C₆₀C₂₄H₃₆N₂(OH)₃₆·5H₂O, and theeverage molecular formula of compound4b (The hydroxylated product of compound 3b) was C₆₀C₃H₇N(OH)₃₈·6H₂O. Compound4a and4b were tested in vitroanti-HIV-1RT activity and vitro anti-HIV-1PR activity. Different degree ofinhibition to HIV-1RT was discovered in the two compounds, the median inhibitoryconcentration(IC50)of HIV-1RT were4a:47.89μg/ml,4b:108.64μg/ml; and fewinhibition to HIV-1PR was discovered in compound4a and4b.