798574-63-7Relevant articles and documents
Halogenated 7-deazapurine nucleosides: Stereoselective synthesis and conformation of 2′ -deoxy-2′ -fluoro-β-D-arabinonucleosides
Peng, Xiaohua,Seela, Frank
, p. 2838 - 2846 (2004)
The stereoselective syntheses of 5-halogenated 7-(2-deoxy-2-fluoro-β- D-arabinofuranosyl)-7 H-pyrrolo[2,3-d]-pyrimidine nucleosides 3b-d, 4a-c as well as 7-deaza-2′-deoxyisoguanosine 2 are described. Nucleobase anion glycosylation of 2-amino-4-chloro-7 H-pyrrolo[2,3-d]pyrimidine (5) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabino-furanosyl bromide (6) exclusively gave the β-D-anomer 7, which was deblocked (→ 8), aminated at C(4) (→ 3a) and selectively deaminated at C(2) to yield 2′-deoxy-2′-fluoro-β-D-arabinofuranosyl 7-deazaisoguanine (2). Condensation of the 5-halogenated 4-chloro-2-pivaloylamino-7 H-pyrrolo[2,3-d]pyrimidines 9a c with 6 furnished the N7-nucleosides 10a-c together with N2, N7-bisglycosylated compounds 11a-c. The former was converted to the corresponding 2,4-diamino-compounds 3b-d, and the latter was deblocked by NaOMe/MeOH to yield the 4-methoxy-nucleosides 4a-c. Conformational analysis of the sugar moiety of the nucleosides 2 and 3a-d was performed on the basis of vicinal [1H,1H] coupling constants. The fluorine atom in the sugar moiety shifts the sugar conformation from S towards N by about 10%, while the halogen substituants in the base moiety increase the hydrophobicity and polarizability of the nucleobases.
