新产品编号:707663

Chemical Name: 2(R,S)-[(1R*,3S*,4S*)-4-(6-Amino-9H-purin-9-yl)spiro[2.2]pent-1-ylmethoxy](phenoxy)phosphorylamino]propionic acid methyl ester; N-[[(1R*,3S*,4S*)-4-(Adenin-9-yl)spiro[2.2]pent-1-ylmethoxy](phenoxy)phosphoryl]-D,L-alanine methyl ester
CAS No. 263137-01-5 (enantiomer)
项目整合开发状态: Biological Testing
项目研究机构: University of Alabama at Birmingham (Originator), University of Michigan (Originator), Wayne State University (Originator), Yale University (Originator)
合成路线:Zinc-catalyzed debromination of dibromo compound (I) afforded the methylene cyclopropane (II).After reduction of the ester group of (II) with LiAlH4,the resulting alcohol (III) was converted to acetate ester (IV) with Ac2O in pyridine.The carbene generated from ethyl diazoacetate in the presence of rhodium catalyst was then added to the olefinic double bond of (IV) to furnish the spirocyclopentane derivative (V) as a mixture of four stereoisomers.Hydrolysis of (V) with NaOH gave rise to the corresponding mixture of stereoisomeric hydroxy acids,which were partially separated by column chromatography to provide a mixture of proximal (VI) and medial-syn (VII) isomers.Acetylation of alcohols (VI) and (VII) gave the corresponding mixture of diastereoisomeric acetates (VIIIa-b).Curtius rearrangement of (VIIIa-b) employing diphenylphosphoryl azide in tert-butanol produced the tert-butyl carbamates (IXa-b).After deacetylation of (IX) using K2CO3 in aqueous MeOH,separation of the isomers by means of column chromatography furnished the desired medial-syn carbamate (X).Removal of the Boc group o (X) was accomplished with HCl in methanol to give the corresponding amine hydrochloride (XI).The purine derivative (XIV) was obtained by alkylation of amine (XI) with 4,6-dichloro-5-nitropyrimidine (XII),followed by treatment of the crude nitro amine (XIII) with SnCl2 and triethyl orthoformate.Cloropurine (XIV) was then converted into adenine derivative (XV) by ammonolysis with methanolic ammonia at 100 C in an autoclave.This was finally coupled with phenyl chlorophosphoroalaninate (XVI) to furnish the title compound.