Condensation of (R)-benzyl 3-hydroxy-13-methyl tetradecanoate (I) with N-Boc-L-isoleucine (II) in the presence of dicyclohexyl carbodiimide and dimethylaminopyridine furnished the corresponding ester (III). After deprotection of the benzyl group of (III) by hydrogenation over Pd/C, the resulting carboxylic acid (IV) was attached to an oxime resin using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) to give the resin-coupled product (V).

Removal of the Boc protecting group of (V) with trifluoroacetic acid was followed by coupling with N-Boc-D-leucine (VI) in the presence of HATU to provide (VII). The deprotection-coupling procedure was repeated using N-Boc-L-aspartic acid gamma-benzyl ester (VIII), N-Boc-L-valine (X), and N-Boc-D-Leucine yielding the depsipeptide resins (IX), (XI) and (XII), respectively.

The deprotection-coupling procedure was repeated using N-Boc-L-leucine (XIII), and N-Boc-L-glutamine (XV), yielding the depsipeptide resins (XII) and (XIV), respectively. Further cleavage of the Boc group provided the deprotected depsipeptide resin (XVII).

Then, liberation from the resin by means of Et3N-AcOH proceded with concomitant cyclization to form the cyclic depsipeptide (XVIII). The benzyl ester group was finally deprotected by hydrogenolysis in the presence of Pd/C.