Structure and conformation of 5-methoxymethyl-2′-deoxycytidine

Abstract

The three-dimensional structure of the antiviral agent 5-methoxymethyl-2′-deoxycytidine (MMdCyd) was deduced by X-ray crystallographic analysis. MMdCyd crystallized in space group P21 with a = 7.9255(6) Å; b = 16.1505(15) Å, c = 10.1861(5) Å, β = 103.801(5)°, and Z = 4 (2 molecules per asymmetric unit); R = 0.044 (Rw = 0.046) for 2560 observed reflections with net I > 3σ(I). The furanose ring adopts the C(3′)-exo envelope conformation (3E) in molecule A and the C(2′)-endo envelope conformation (2E) in molecule B. In the sugar ring of both crystallographically independent molecules A and B, the side chain at C(5′) has the g+ conformation. This appears to be a preferred geometry required for antiherpes activity in 2′-deoxyribonucleosides. The glycosyl linkage is anti with χ = 213.7° for the A molecule and 222.2° for the B molecule. With respect to this anti conformation, the methoxy group at C(5) in molecules A and B exhibits different conformations; it is on the same side of the pyrimidine plane as the deoxyribofuranose ring oxygen (O4′) in molecule B and on the opposite side in molecule A. Keywords: antiherpes agent, conformation, 5-methoxymethyl-2′-deoxycytidine, crystal structure.