Paecilodepsipeptide D (1), a new cyclohexadepsipeptide was isolated together with known paecilodepsipeptidesA–C (2–4) from the whitefly pathogenic fungus Conoideocrella luteorostrata BCC 76664. The structure of 1 waselucidated by spectroscopic analyses and was further confirmed by the chemical correlation to paecilodepsipeptideA (2) by converting both compounds into the same di-O-prenyl derivative (5). A comparison of the antimalarialactivities of 1, 2, and 5 suggested that a polar phenolic (OH) functionality at the D-tyrosine (Tyr-2) is crucial for theantimalarial activity, while a lipophilic O-alkyl side-chain at the other D-tyrosine (Tyr-1) is preferred.