新产品编号:1868851

Chemical Name: [(1S,3S)-3-(6-Amino-9H-purin-9-yl)-1-fluorocyclopentyl]methanol; L-(1'S,3'S)-9-[3-Fluoro-3-(hydroxymethyl)cyclopentyl]adenine
项目整合开发状态: Biological Testing
项目研究机构: University of Georgia (Originator)
合成路线:Horner-Emmons condensation of 2,3-isopropylidene-D-glyceraldehyde (I) with phosphonate (II) produced the unsaturated ester (IIIa-b).Ketal deprotection and lactone ring closure of (II) under acidic conditions,followed by O-silylation afforded (IV).The lactone function of (IV) was reduced with DIBAL and then with NaBH4-CeCl3 to produce the corresponding diol.Further silylation of the primary hydroxyl group furnished (V).Condensation of (V) with triethyl orthoacetate followed by Claisen rearrangement gave rise to the gamma,delta-unsaturated ester (VI).This was reduced to alcohol with LiAlH4 and then alkylated with benzyl bromide to yield benzyl ether (VII).Ozonization of (VII) in methanol at -78 C,followed by decomposition of the ozonide with dimethyl sulfide gave aldehyde (VIII).Horner-Emmons condensation of (VIII) with the sodium salt of triethyl phosphonoacetate (IX) produced the alpha,beta-unsaturated ester (X).Double bond hydrogenation in (X) with simultaneous benzyl group cleavage afforded hydroxy ester (XI),which was then converted to mesylate (XII).This was cyclized to the cyclopentane (XIIIa-b) by means of NaH in refluxing THF.

合成路线:Hydrolysis of (XIIIa-b) to the carboxylic acid (XIVa-b),and further iodo decarboxylation yielded a mixture of epimeric iodides (XVa-b).From hydrolysis of the iodide group of (XVa-b) with NaHCO3 only the alpha-alcohol (XVI) was isolated.This was condensed with 6-chloropurine (XVII) under Mitsunobu conditions to give adduct (XVIII).The 6-chloro derivative (XVIII) was converted into the protected adenosine analogue (XIX) by treatment with methanolic ammonia in a steel bomb at 100 C.Finally,desilylation of (XIX) employing tetrabutylammonium fluoride furnished the title compound.