Synthesis And Anti-HIV Properties Of Novel Fulleropyrrolidines Prepared From C₆₀ And Dehydroabietylamine Derivatives

Fullerene (C₆₀) and its derivatives have exerted great impacts in physics,chemistry and material sciences due to their particular structures and properties.They also have showed tempting prospects in medicinal chemistry because of theirspecial activities which enable them to be potential candidates in treatment of somediseases such as AIDS, cancer and so on. Dehydroabietylamine possesses aromaticditerpene structure and unique antibacterial activity. It is valuable to combine C₆₀with dehydroabietylamine derivatives and explore biochemical activities of the newmolecules.In this paper, N-carboxymethyl-12-acetyldehydroabietylamine andN-carboxymethyl-12,14-dinitrodehydroabietylamine (2a and2b) were synthesizedby the hydrolysis of two novel glycine methyl esters with LiOH in THF/water, whichwere prepared through nucleophilic substitution of methyl chloroacetate and12-acetyldehydroabietylamine (or12,14-dinitrodehydroabietylamine) catalysised byEt3N at85℃in1,2-dimethoxyethane. Their structures were characterized by IR,1HNMR,¹H NMR, and ESI-TOF-MS.The1,3-dipolar cycloaddition reaction was also researched in this paper. Twonovel fulleropyrrolidines with dehydroabietylamine groups containing differentsubstituents on the phenyl moiety which have never been reported before, weresynthesized by reaction of C₆₀, paraformaldehyde and2a (or2b) by refluxing intoluene. The products were fully characterized by IR,1H NMR,¹H NMR andMALDI-TOF-MS, and were further confirmed by HSQC, HMBC and1H-1H COSY.The assignments of all the resonances were also specified by2D NMR spectra.Moreover, two water-soluble cationic fullerene derivatives (4a and4b) weresynthesized in toluene at room temperature under dark for3days by reaction ofiodomethane and bis-fulleropyrrolidines made by the1,3-dipolar cycloaddition ofdehydroabietylamine-C₆₀derivatives, paraformaldehyde and sarcosine. The resultcompounds, which were the mixture of different molecules containing severalpyrrolidines on the carbon cages, were characterized by IR,1H NMR andMALDI-TOF-MS.Then, the inhibitory activities against HIV-1protease and HIV-1reversetranscriptase of2a,2b,4a and4b were evaluated in this paper. The preliminary test displayed2a and2b showed few inhibition to HIV-1PR and HIV-1RT while4a and4b had great anti-HIV activities. IC50of HIV-1PR and HIV-1RT of4a are4.04μg/mL and15.76μg/mL, respectively, while4b are2.88μg/mL and7.77μg/mL,respectively.