Nucleosides, Nucleotides & Nucleic Acids 2008-08-01

Synthetic studies on formamidopyrimidines related to clofarabine.

William R Cantrell, Dennis Lovett, Tracy Engles, Bruce Anderson, William E Bauta, Paul C Wolstenholme-Hogg

Index: Nucleosides Nucleotides Nucleic Acids 27(8) , 901-13, (2008)

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Abstract

Degradation of clofarabine (3) in 0.9% saline solution at 100 degrees C afforded three degradation products which were determined to be formamidopyrimidines 4-6. Compounds 4 and 5 were assigned as C(1') anomers on the basis of one-dimensional and two-dimensional NMR experiments, whereas 6 was found to be the formamidopyrimidine lacking the sugar moiety. An improved procedure for the synthesis of formamidopyrimidines was developed, wherein benzoylated clofarabine (11) was treated with allyl chloroformate, followed by deprotection of the alloc group with catalytic Pd(PPh(3))(4) and dimedone. A synthesis of compound 6 from 4 is also described.