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 EC 50 value of 1.17 ± 0.19 μM.