Synthesis of 18‐Demethoxy Analogues of the Aglycon of Saundersiosides A and B, Based on a Cascade Process

A deprotection/retro‐vinylogous aldol/vinylogous aldol/intramolecular transesterification/O‐Michael cascade triggered by Bu4NF was found to lead to a hexacyclic lactone in high yield on gram scale. This intermediate was used to prepare several 18‐demethoxy analogues of the aglycon of saundersiosides A and B. Pull the trigger! Bu4NF removed the C16‐TBDPS group and triggered a retro‐vinylogous aldol/vinylogous aldol process to invert the configuration of C16α‐OH, the C16β‐OH underwent an intramolecular transesterification, and the newly exposed C18‐OH attacked back via an O‐Michael reaction, delivering a hexacyclic intermdiate, which was converted to several demethoxy analogues of the aglycon of saundersiosides A and B.