Non-phenolic dicinnamamides from Pholiota spumosa: Isolation, synthesis and antitumour activity

Two new amides derived from cinnamic acid, namely, (R)-2-hydroxyputrescine dicinnamamide (4) and pholiotic acid {(2R)-2-[(S)-3-hydroxy-3-methylglutaryloxy] putrescine dicinnamamide} (5), in addition to the known compound maytenine (N¹,N⁸-dicinnamoyl spermidine) (3) were isolated from the fruiting bodies of the Basidiomycete Pholiota spumosa. The absolute configuration of 4 was established as (R) by its total synthesis starting from (S)-dimethylmalate, whereas that of 5 was determined by conversion into the known compound methyl (S)-4-[(S)-1-(1-naphthalen-1-yl)-ethylcarbamoyl]-3- hydroxy-3-methylbutanoate (14). Compounds 3 and 5 exhibited an inhibitory effect on cell growth of the androgen-insensitive DU-145 prostate cancer cells, which suggests that these fungal polyamine conjugates, like other polyamine analogues, might have chemotherapeutic potential against androgen-independent prostatic cancer.