ABSOLUTE-CONFIGURATION OF NOVEL MARINE DITERPENOID UDOTEATRIAL HYDRATE SYNTHESIS AND CYTOTOXICITIES OF ENT-UDOTEATRIAL HYDRATE AND ITS ANALOGS

Antipode of novel marine diterpenoid udoteatrial hydrate was synthesized from (+)-genipin as a chiral building block via homogeranyl lactone obtained by an 1,4-addition of lithiated geranyl sulfone to the key intermediate, exomethylene lactone. The stereochemistry of newly formed stereogenic center at C5 was carefully examined by comparing H-1-NMR spectra of each diastereomer of homogeranyl lactones with those of model compounds, stereochemistries of which were confirmed by single crystal X-ray determination. The exomethylene lactone was successfully prepared from genipin through a catalytic hydrogenation Of C6-C-7 double bond in cyclopentene ring in genipin. Our synthesis culminating the synthesis of antipode of udoteatrial hydrate could confirm the absolute configuration of udoteatrial hydrate as (2aS, 4aS, 5S, 7bR). The analogues of antipode of udoteatrial hydrate were also synthesized from exomethylene lactone. Those analogues were subjected to the cytotoxic assay to find that diacetates of analogues involving homogeranyl side chain were cytotoxic against human carcinoma KB and A-549 cells in vitro.