Drymariamides A–J, Antiadipogenic Cyclopeptides Incorporating Noncanonical Amino Acids from Drymaria cordata

Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A–J (1–10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey’s method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1–10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 μM.