Synthesis And Biological Activity Of Some Ring-C And Ring-B Derivatives From Dehydroabietylamine

Considering the special tricyclic structure and amino group, and exhibit good biologicaland optical activity, dehydroabietylamine was proved to be a useful starting material forexploring its derivatives, including synthese and evaluation. We synthesized some novel ring-Band ring-C derivatives from dehydroabietylamine, and their structure were characterized byFT-IR,1H NMR,13C NMR and MS, while their biological activities were also evaluated.Dehydroabietylamine acetanilide derivatives at ring-C were synthesized. The startingmaterial, dehydroabietylamine, was proteced by tetrachlorophthalic anhydride (TCPA), thentransformed into acetanilides by Friedel-Crafts acylation, oximation and Beckmannrearrangement, the acetylamine group was introduced at ring-C on C-12, finally,12-acetamidodehydroabietylamine derivatives were treated with hydrazine monohydrate todeprotection. Compared with conventional scheme via nitration at ring-C, nitro reduction andthen acetylation, this novel method provided higher yield and selectivity. The influence ofchanging Friedel-Crafts acylation reaction conditions (the amount of AlCl3and reactiontemperature) for acylation products was also studied, which whether would lead to deisopropylat ring-C..Then, dehydroabietylamine1,2,3-thiadiazole derivatives were synthesized, started fromdehydroabietylamine, after protected amino group by trifluoroacetic anhydride or aceticanhydride, the subsequnce was transformed into ketones by chromic oxidation, ketones reactedwith semicarbazide hydrochloride in refluxed ethanol to afford semicarbazones, thenHurd-Mori reaction occured in the processing of thionyl chloride to afford1,2,3-thiadiazolederivatives, the amide hydrolysised under basic conditions to remove protecting groups.In this paper, we also studied two new syntheted compounds N,N-(tetrachlorophthaloyl)-12-acetyl-13-deisopropyldehydroabietylamine (3a) and N-trifluoroacetyldehydroabietylamine-7-oxo(6a) reacted with Vilsmeier reagent, the results showed that they chloroformylated andchloridized respectively and afforded N,N-(tetrachlorophthaloyl)-12-(Z-2-formyl-1-chloro-vinyl)-13-deisopropyldehydroabietylamine (10) and N-trifluoroacetyldehydroabietylamine-(6,7-ene)-7-chloro (11).The biological activity of the syntheted derivatives from dehydroabietylamine wasexplored, tested their anti-Alzheimer disease activity and anti-tumor activity. The resultsshowed that they did not had significant effects of anti-Alzheimer disease, but they did hadcertain effects of anti-tumor, espacially compound N-acetyldehydroabietylamine-6-ene[7,6-d][1,2,3]thiadiazole (8b) and dehydroabietylamine-6-ene[7,6-d][1,2,3]thiadiazole (9),which possess1,2,3-thiadiazole moity, had relatively high inhibit LLC cell activity even at lowconcertration(about49%and51.4%respectively under0.405μM and0.9μM).