Synthetic secofriedelane and friedelane derivatives as inhibitors of human lymphocyte proliferation and growth of human cancer cell lines in vitro.

ABSTRACT

Controlled silylation of friedelin (1) from cork smoker wash solids, a byproduct generated during processing of corkboard by steam baking, gave 3-trimethylsiloxyfriedel-2-ene (3) in high yields. Oxidation of 3 with OsO(4)/NMMO produced 2alpha-hydroxyfriedelan-3-one (cerin) (5), from which the new 2,3-secofriedelan-2-al-3-oic acid (6) was obtained quantitatively by periodic acid oxidation. Oxidation of 3 with DDQ afforded friedel-1-en-3-one (8). Reductive ozonolysis of 3 gave 2alpha,3beta-dihydroxyfriedelane, pachysandiol A (7). Compound 6 proved to be a potent inhibitor of human lymphocyte proliferation (IC(50) = 10.7 microM) and of the growth of a human cancer cell line (GI(50) = 5.4-17.2 microM). (13)C NMR data for compounds (3, 4, 5, 6a,7, and 8) are described for the first time.