In nucleosides, at the position where the base (9-deazapurine in this case) is attached, two isomers (α and β) are possible and only β isomers of nucleosides have been found biologically active.
9-deazapurine derivatives represented by the following structural formula:
wherein:    X=NH, O, or S;    R=Benzyl, substituted benzyl such as 2,4-dichlorobenzyl, hydrogen, alkyl such as tert-butyl; or silyl such as tert-butyldimethylsilyl or tert-butyldiphenylsilyl;    R1=H, OH, NH2, Cl, NR5R6, alkyl, aryl, alkenyl, or alkynyl;    R2=H, NH2, NHR7, or S-alkyl;    R3=H, Alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, or substituted alkynyl;    R4=H, OH, N3, or NH2;    R5 and R6 independently are =H, alkyl, aryl, or both together with nitrogen can form a heterocyclic or substituted heterocyclic ring;    R7=alkyl, acyl, or carbamate; and pharmaceutically acceptable salts thereof, are useful as antiviral and anticancer agents.
Various methods for the preparation of these 9-deazapurine derivatives have been described. For instance, methods for the preparation of compounds of structure I wherein R=H, R1=OH, NH2, R2=NH2, R3=H, R4=OH are described in following:                1. Klein et al. U.S. Pat. No. 4,584,369 (1986).        2. Bhattacharya et al. Nucleosides and Nucleotides 9(8), 1021-1043 (1986).        3. Bhattacharya et al. Tetrahedron letters 27(7), 815-818 (1986).        4. Ren et al. J. Org. Chem. 47, 4633-4637 (1982).        5. Tam et al. J. Heterocyclic Chem. 13, 1305-1308 (1976).        6. Lim et al. J. Org. Chem. 48, 780-788 (1983).        7. Chun et al. J. Org. Chem. 66, 4852-4858 (2001).        8. Cupps et al. J. Org. Chem. 51, 1058-1064 (1986).        
All the above mentioned references have used isopropylidene group as a protecting group for 2- and 3-hydroxyl groups in ribose. When further reactions to prepare 9-deazapurine derivatives are carried out with this protecting group, it results in a mixture of α and β isomers in the approximate ratio of 1:2 to 1:1. In structure I when R3=CH3, and the isopropylidene group is used as the protecting group, the ratio of α and β is 9:1.
Accordingly, prior processes suffer from the inability to selectively produce the β isomer as the predominant isomer.
USPTO Backgrounds
USPTO Backgrounds