新产品编号:1636297

Chemical Name: N-[(2R,3R,4R,5R)-3,4-Dihydroxy-5-(hydroxymethyl)-1-methyl-2-pyrrolidinylmethyl]acetamide
项目整合开发状态: Biological Testing
项目研究机构: Inst. Physical Chemical Res. (RIKEN) (Originator), Scripps Research Institute (Originator)
合成路线:The condensation of benzylated D-arabinofuranose (I) with phosphonate (II) in benzene gives the unsaturated ester (III),which is reduced with DIBAL in dichloromethane,yielding the alcohol (IV).The selective monosilylation of (IV) with Tbdms-Cl,TEA and DMAP in DMF affords the silyl ether (V),which is treated with chloromethylsulfonyl chloride and pyridine to provide the sulfonate (VI).The reaction of (VI) with CsOAc and a crown ether in toluene gives the acetate (VII) with inversion of the configuration at the acetoxy group.Hydrolysis of the acetate group with NaOMe in THF yields the alcohol (VIII),which is chloromesylated as before,affording the sulfonate (IX).The treatment of (IX) with HCl in THF eliminates the silyl group,providing the unsaturated alcohol (X),which is epoxidized with tBu-OOH,Ti(OAc)4 and D-(-)-diethyl tartrate to give the chiral epoxide (XI).The reaction of (XI) with sodium azide in DMF yields the azido compound (XII) with the correct steric configuration.The reductive cyclization of (XII) with PPh3,H2 and Pd/C in methanol affords the pyrrolidine (XIII),which is N-protected with Boc2O and TEA in dichloromethane,providing the carbamate (XIV).Oxidative cleavage of the vicinal diol of (XIV) with Pb(OAc)4 in toluene gives the carbaldehyde (XV).

合成路线:The reduction of aldehyde (XV) with DIBAL in dichloromethane gives the carbinol (XVI),which is treated with Ms-Cl and TEA to yield the mesylate (XVII).The reaction of (XVII) with sodium azide in DMF affords the corresponding azide (XVIII),which is reduced with H2 over Pd/C in methanol to provide the amino compound (XIX).The reaction of (XIX) with Ac2O in pyridine gives the expected amide (XX),which is treated with TFA to eliminate the carbamate protecting group,thus yielding pyrrolidine (XXI).The reductive methylation of (XXI) with formaldehyde and NaBH3CN in methanol affords the N-methylated pyrrolidine (XXII),which is finally deprotected by hydrogenation with H2 over Pd/C in methanol.