Structures, biogenetic relationships, and cytotoxicity of pimarane-derived diterpenes from Petalostigma pubescens

Abstract

Extraction of Petalostigma pubescens heartwood followed by chromatographic purifications and crystallizations afforded five tricyclic diterpenes: 5,9-syn-rosanes petalostigmones A and B ( 1 and 2), the erythroxylane petalostigmone C ( 3), the norditerpene lactone pubescenone ( 4), and the known ent-cleistanthane diterpene (−)-sonderianol ( 5). The structures and relative stereochemistry were elucidated by means of spectroscopic methods, chemical correlations, and, in the cases of 1 and 4, by X-ray crystallographic analyses. The new isolates 1– 4 are assumed to belong to the same absolute configurational family (9αCH 3) of ent-pimarane-derived diterpenes as the known co-occurring (−)- 5 (10αCH 3). Biogenetic schemes originating from a common ent-copalyl diphosphate intermediate are presented to rationalize the structures of these natural products. A novel ring contraction–ring expansion mechanism is suggested to account for the 7-membered B ring of pubescenone. Compounds 1– 5 were evaluated for their cytotoxicity; sonderianol ( 5) showed the highest activity against mouse leukemia cell lines L1210, P388 and mouse liver cancer cells HEPA1c1c7.