Synthesis and biological evaluation of aromatic analogues of comduritol F, L-chiro-inositol, and dihydroconduritol F structurally related to the Amaryllidaceae anticancer constituents

Pancratistatin is a potent anticancer natural product, whose biol. evaluation is hampered by the limited natural abundance and the stereochem. complex structure undermining practical chem. prepn. Fifteen arom. analogs of conduritol F, L-chiro-inositol, and dihydroconduritol F that possess four of the six pancratistatin stereo-centers have been synthesized and evaluated for anticancer activity. These compds. serve as truncated pancratistatin analogs lacking the lactam ring B, but retaining the crucial C10a-C10b bond with the correct stereochem. The lack of activity of these compds. provides further insight into pancratistatin's min. structural requirements for cytotoxicity, particularly the criticality of the intact phenanthridone skeleton. Significantly, these series provide rare examples of simple arom. conduritol and inositol analogs and, therefore, this study expands the chem. and biol. of these important classes of compds.