Total Synthesis and Stereochemistry of ( + ) - Phyllanthocindiol 843 Paul

The crude ethanol extract obtained from the root of Phyllanthus acuminatus Vahl was found to inhibit growth in the P388 leukemia system in mice. Kupchan and coworkers traced the significant pharmacological properties to a bisabolane sesquiterpene glycoside, (+)-phyllanthoside (0' Although the structure of the corresponding aglycon (+)-phyllanthocin (2) was elucidated by single-crystal X-ray diffraction, the exact nature of the sugar moiety in 1 and the absolute configuration of 1 and 2 remained unknown. Recently, Pettit and co-workers determined the structure of phyllanthose, the novel disaccharide portion of 1 (Chart I), as well as the structure of phyllanthostatins I (3) and I1 (4) and the partial structure of phyllanthostatin I11 (5).2,3 Although the total synthesis of 2 allowed us to determine the absolute configuration of this series? the relative stereochemistry of the vicinal diol moiety in 5 remained undetermined. We report herein the details of a total synthesis of (+)-phyllanthocindio1(6), the hitherto unreported aglycon portion of phyllanthostatin I11 (5), demonstrating that the absolute and relative stereochemistries of 5 and 6 are as drawn.4b