Synthetic Studies on Formamidopyrimidines Related to Clofarabine

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.

Applications of Purine Ring Opening in the Synthesis of Imidazole, Pyrimidine, and New Purine Derivatives

“…A selective cleavage of Alloc-protecting group with Pd 0 subsequently produced FAPY 256 in 30 % yield calculated from adenine 254 (Scheme 42). [173] Sodium sulfide is known to be used for the removal of PNB group, but in the case of imidazolium 258 hydroxyl mediated ring opening occurred instead of protecting group removal and the PNB protected FAPY 259 was obtained (Scheme 43). [174] FAPY fragments are also found in natural products, for example, agelasines 260 a-c are bioactive purine derivatives with terpene side chain found in marine sponges of genus Agelas.…”

“…A selective cleavage of Alloc‐protecting group with Pd 0 subsequently produced FAPY 256 in 30 % yield calculated from adenine 254 (Scheme 42). [173] …”