Structure-activity relationship study of the anti-obesity natural product yoshinone A

Yoshinone A was derived from marine algae and shown to inhibit adipogenic differentiation. The natural compound is composed of a γ-pyrone ring and a side chain and that contains two asymmetric carbons. Although their absolute configuration has been determined, there is no information available on the stereoisomers and their bioactivities. To address this question, we synthesized all four stereoisomers and measured their activities. We also prepared three more derivatives of yoshinone A and found that the stereo-configuration inside the side chain, the γ-pyrone ring, and bulkiness of the side chain all played important roles in its activity. Our findings should help to elucidate the mechanism of action of yoshinone A.