N-4909

Chemical Name: N2-[3(S)-Hydroxy-13-methyltetradecanoyl]-L-glutaminyl-L-leucyl-D-leucyl-L-valyl-L-aspartyl-D-leucyl-L-isoleucine O-3.1-C-1.8-lactone
项目整合开发状态: Biological Testing
项目研究机构: Nisshin Pharma (Originator)
合成路线: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).

合成路线: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.

合成路线: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).

合成路线: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.