Clusiaceae and Calophyllaceae are pantropical plants well known to biosynthesize polyprenylated polyphenols [1]. Among them, several xanthones, coumarins and benzophenones have shown anti-inflammatory or immunomodulatory properties [2 – 3]. In order to identify natural products exhibiting potential anti-inflammatory and immunosuppressive activities, a dereplication analysis was conducted through HPLC-PDA-MSn on the DCM and MeOH extracts (bark, leaves and occasionally fruits) obtained from nine Calophyllum and three Mesua species (Calophyllaceae) native to Malaysia. It appeared that the fruits of Mesua lepidota T. Anderson are a rich source of original phenylcoumarins named as lepidotols and lepidotins. A biosynthetic hypothesis accompanied with experimental and calculated specific rotations were used to determine the stereochemistry of these compounds. The lepidotol series was also detected in the bark and in another Mesua species. References: [1] Cechinel Filho V et al. Chem Biodivers 2009; 6: 313 – 327. [2] Anantachoke N et al. Pharm Biol 2012; 50: 78 – 91. [3] Fu Y et al. J Agric Food Chem 2014; 62: 4127 – 4134.