The regioselective opening of the ring E in spirostan sapogenins provides new dihydropyran derivatives. This novel side chain is obtained after a Lewis acid mediated acetolysis followed by an alkaline workup. The reaction mechanism is analyzed via density functional theory computations, and both experimental and computational data support the formation of an oxacarbenium intermediate. The behavior of the title skeletons under acidic conditions is also investigated.

Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure–activity relationship study, two new analogs, ZJ-105 and ZJ-106, were designed and synthesized to probe the importance of the conjugated trienyl lactone moiety of the molecule by replacing the C2–C3 double bond in ZJ-101 with a single bond and switching the geometry of the C4–C5 double bond in ZJ-101 from Z to E, respectively. Biological evaluation showed that ZJ-105 completely loses antiproliferative activity whereas ZJ-106 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the conjugated trienyl lactone moiety of the molecule is critical for its anticancer activity.

Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure–activity relationship study, a new analog ZJ-102 was designed and synthesized to probe the importance of the cyclohexenyl group through its replacement to a phenyl group using a concise and convergent synthetic approach. The biological evaluation showed that this new analog ZJ-102 is significantly less active against cancer cells in vitro than ZJ-101, suggesting that the cyclohexenyl ring (along with its two stereogenic centers) present in ZJ-101 is important for its anticancer activity.

Compound ZJ-101, a structurally simplified analog of the marine natural product superstolide A, was previously developed in our laboratory. In the subsequent structure–activity relationship study, a new analog ZJ-109 was designed and synthesized to probe the importance of the lactone moiety of the molecule by replacing the lactone in ZJ-101 with a lactam. The biological evaluation showed that ZJ-109 is about 8–12 times less active against cancer cells in vitro than ZJ-101, suggesting that the lactone moiety of the molecule is important for its anticancer activity.

Regio-, stereo-, and facial selective [4 + 2] cycloadditions between highly activated vinyl sulfones and 1,3-dienes derived from (R)-4-tert-butyldimethylsilyloxy-2-cyclohexen-1-one provide a powerful approach for the asymmetric synthesis of compounds containing the bicyclo[2.2.2]octanone carbon skeleton. This new methodology has been successfully applied to the asymmetric synthesis of the cis-decalin core structure of the potent anticancer marine natural products superstolides A and B.

OSW-1 is a highly potent anticancer natural saponin with an unknown mode of action. To determine its cellular target(s) biotinylated OSW-1 was successfully synthesized in nine steps.OSW-1 is a highly potent anticancer natural saponin with unknown mode of action. To determine its cellular target(s) biotinylated OSW-1 was successfully synthesized in nine steps.