Adamantyl-SNO, NMI-1165

Chemical Name: N,N-Dimethyl-2-[2-(nitrososulfanyl)adamant-2-yl]acetamide
项目整合开发状态: Preclinical
项目研究机构: NitroMed (Originator)
合成路线:Paclitaxel (I) is selectively protected at the side-chain hydroxyl group with 2,2,2-trichloroethyl chloroformate in pyridine to afford the carbonate ester (II).Subsequent acylation of (II) with 3-methyl-3-[(2,4,6-trimethoxybenzyl)thio]butyric acid (III) provides ester (IV).Removal of the trimethoxybenzyl protecting group of (IV) by means of formic acid in the presence of L-cysteine gives rise to thiol (V).

合成路线:The trichloroethyl carbonate ester of (V) is then reductively cleaved using zinc dust and HOAc,to produce (VI).Finally,nitrosation of the thiol group of (VI) by means of t-butyl nitrite furnishes the target nitrosothio derivative.

合成路线:Thionation of 2-adamantanone (I) by means of P4S10 gives thioketone (II).Subsequent addition of tert-butyl acetate to thioadamantanone (II) furnishes the beta-mercapto ester (III).After acidic cleavage of the tert-butyl ester of (III),the resultant mercapto acid (IV) is cyclized to the thiolactone (V) by using EDC.Subsequent lactone ring opening in (V) with dimethylamine gives rise to amide (VI).Finally,the thiol group of (VI) is nitrosated with tert-butyl nitrite to provide the desired nitrosothio compound.