[18F]-N-Me-FAMP

Chemical Name: 3-([18F]Fluoro)-2-methyl-2-(methylamino)propionic acid
项目整合开发状态: Preclinical
项目研究机构: Emory University (Originator)
合成路线:The nonradioactive aminoacid is prepared as follows.The Strecker reaction of fluoroacetone (I) with KCN and NH4Cl provides amino nitrile (II).Acid hydrolysis of (II) gives aminoacid (III),which is further protected as the N-Boc derivative (IV) by using di-t-butyl dicarbonate.Treatment of acid (IV) with t-butyl trichloroacetimidate produces the t-butyl ester (V).Subsequent alkylation of (V) with iodomethane and NaH affords the N-methyl derivative (VI).The protecting groups of (VI) are finally removed by acidic hydrolysis to produce the free aminoacid.

合成路线:The [18F]-labeled compound is prepared as follows.Benzyloxy acetone (I) is treated with KCN and buffered (NH4)2CO3 to produce hydantoin (II).Alkaline hydrolysis of (II),followed by treatment of the crude aminoacid (III) with Boc2O gives the Boc-protected aminoacid (IV).The esterification of (IV) by means of t-butyl trichlroacetimidate affords the t-butyl ester (V),which is N-methylated with MeI and NaH to give compound (VI).Catalytic hydrogenolysis of the benzyl ether group of (VI) yields alcohol (VII).Selective removal of the N-Boc group of (VII) in the presence of the t-butyl ester to furnish (VIII) is achieved with p-toluenesulfonic acid in hot ethanol.Reaction of amino alcohol (VIII) with SOCl2 produces the cyclic sulfamidite (IX),which is further oxidized to sulfamidate (X) with NaIO4 in the presence of a catalytic amount of RuO2.The radiolabeled aminoacid is then obtained by treatment of (X) with [18F]-fluoride,followed by acidic cleavage of the t-butyl ester group.