MAG-283

Chemical Name: 2(R)-[4-Amino-4-oxo-2(S)-sulfanylbutyl]sulfanyl]-N-[1(S)-benzyl-2-(methylamino)-2-oxoethyl]-4-methylpentanamide; N2-[2(R)-[4-Amino-4-oxo-2(S)-sulfanylbutylsulfanyl]-4-methylpentanoyl]-N1-methyl-L-phenylalaninamide
项目整合开发状态: Biological Testing
项目研究机构: Aventis Pharma (Originator), Florida State University (Originator), National Institutes of Health (Originator)
合成路线:Diazotization of D-asparagine (I) in the presence of KCl afforded (R)-2-chlorosuccinamic acid (II) with retention of the configuration.Subsequent displacement of the chlorine atom of (II) with tert-butyl mercaptan provided thioether (III).Reduction of the carboxyl group of (III) by means of borane in THF gave alcohol (IV),which was converted to thioester (V) by esterification with thioacetic acid under Mitsunobu conditions.The chiral bromo acid (VII) (prepared by diazotization of L-leucine (VIII) in the presence of KBr) was then condensed with the thiol liberated from thioacetate (V) in the presence of NaOEt,yielding the corresponding thioether (VIII).Coupling of N-methyl-L-phenylalaninamide (IX) with carboxylic acid (VIII) using DCC and HOBt gave rise to amide (X).The S-tert-butyl group of (X) was then removed by means of 2-nitrobenzenesulfenyl chloride (XI) in HOAc,generating the disulfide (XII).Finally,the disulfide bond of (XII) was reductively cleaved with 2-mercaptoethanol to furnish the title thiol.