A formal total synthesis of 5/5/5/6 caged-like daphnenoid A was accomplished. The strategy involves a Morita-Baylis-Hillman reaction to construct a precursor for the key intramolecular Diels-Alder reaction (IMDA). Notably, the IMDA indicated opposite chemoselectivity when the configuration of stereocenter (C7) changed. Several intermediates we synthesized showed stronger anti-inflammation activities compared to daphnenoid A.
Zhang et al. (Thu,) studied this question.