合成路线1

The addition of ethyl diazoacetate (II) to 2,3-dibromopropene (I) catalyzed by dirhodium tetraacetate in CH2Cl2 yielded a mixture of E- (III) and Z- (IV) cyclopropanes. Alkylation of adenine (V) with the mixture of bromoesters (III) and (IV) in the presence of either NaH in DMF at r.t. or K2CO3 at 80 C provided the diastereomeric (cyclopropylmethyl)adenines (VI). Elimination of HBr was carried out with potassium tert-butoxide in cold DMF or with NaH in THF to yield an unseparable mixture of Z- (VII) and E- (VIII) methylene cyclopropanes. Alternatively, simultaneous alkylation of adenine (V) and elimination of HBr to give (VII) + (VIII) was effected using K2CO3 in DMF at 100 C. Reduction of the ester groups of (VII) and (VIII) with DIBALH afforded a mixture of the racemic (Z) title compound (IX) and its its E-isomer (X). The unseparable mixture of (IX) and (X) was treated with dimethylformamide dimethylacetal in DMF to give the corresponding (dimethylamino)methylene derivatives that allowed a chromatographic separation. The desired racemic (Z)-isomer (XI) was further deprotected in methanolic ammonia to furnish racemic (IX) (1). Optical resolution was then achieved on treatment with adenosine deaminase, to produce the (Z)(S)-(+)-hypoxanthine derivative (XII) that was separated chromatographically from the unchanged (Z)(R)-(-)-isomer, the target compound.