TAK-726

(2S,3S)-N-[(1S)-1-甲酰基-2-(1H-吲哚-3-基)乙基]-3-甲基-2-[(1-萘基磺酰基)氨基]戊酰胺Chemical Name: 1-Naphthylsulfonyl-L-isoleucyl-L-tryptophanal
CAS No. 161709-56-4
项目整合开发状态: Preclinical
项目研究机构: Takeda (Originator)
合成路线:Title compound was prepared by two related ways:N-(Benzyloxycarbonyl)-L-tryptofanol (I) was deprotected by hydrogenolysis in the presence of Pd/C.The resulting tryptofanol (II) was then coupled with N-(benzyloxycarbonyl)-L-isoleucine (III),using 1-(3-diethylaminopropyl)-3-ethylcarbodiimide.HCl (EDC) and 1-hydroxybenzotriazole (HOBt) to provide (IV).Subsequent hydrogenolytic deprotection gave amine (V),which was condensed with 1-naphthalenylsulfonyl chloride (VI) in the presence of 4-(dimethylamino)pyridine to afford sulfonamide (VII).Finally,oxidation with DMSO in the presence of SO3-pyridine complex yielded the aldehyde.

合成路线:Alternatively,N-(benzyloxycarbonyl)-L-Trp (VIII) was condensed with N,O-dimethylhydroxylamine in the presence of EDC and HOBt to give N-(methoxy)amide (IX).Hydrogenolytic deprotection produced amine (X),which was coupled with Z-Ile (III) to afford dipeptide (XI).Subsequent deprotection,and coupling of the resulting amine (XII) with sulfonyl chloride (VI) gave sulfonamide (XIII).Then,reduction of the N-(methoxy)amide with diisobutylaluminum hydride furnished the target aldehyde