Nonpeptide Small Molecules with a Ten-Membered Macrolactam or a Morpholine Motif from the Insect American Cockroach and Their Antiangiogenic Activity

(±)-Periplactam A (1), rare ten-membered macrolactam composed of lignan and putrescine, (±)-periplanol E (2), a dimeric phenethyl alcohol derivative formed via morpholine, and periplactams B (3) and C (4), epimeric adducts composed of isocoumarin and urea, were isolated from American cockroach (Periplaneta americana). Their structures were identified by spectroscopic analyses, X-ray diffraction, and computational methods. Biological assay revealed that (+)-2 exhibits antiangiogenic activity in HUVECs in a dose-dependent manner.