Stereochemistry of the DBU/LiCl-Assisted Nucleophilic Substitution at Phosphorus in Nucleoside-3‘-O-(Se-methyl Methanephosphonoselenolate)s†
1998-07-15T00:00:00Z (GMT) by
The crystal and molecular structure of diastereomerically pure N4-benzoyl-2‘-deoxycytidine 3‘-O-(Se-methyl methanephosphonoselenolate (FAST-eluted) (4, R = H, B = CBz) and 5‘-O-pixylthymidine 3‘-O-(S-methyl methanephosphonothiolate (FAST-eluted) (5) have been elucidated by X-ray crystallography. The absolute configuration at the phosphorus atom in both compounds is SP. Each FAST-4‘ (R = DMT, B = CBz) and FAST-5 (R = Px, B = Thy) in the process of DBU/LiCl-assisted condensation with 3‘-O-acetyl-N4-benzoylcytidine and 3‘-O-acetylthymidine gave after deprotection (SP)-dicytidine-(3‘,5‘)-methanephosphonate and (SP)- dithymidine-(3‘,5‘)-methanephosphonate, respectively. Unambiguous assignment of the absolute configuration at the phosphorus in 4 (R = H, B = CBz) and 5 (R = Px, B = Thy) allows for stereochemical correlation and the conclusion that DBU/LiCl-assisted nucleophilic substitution at phosphorus occurs with net inversion of configuration, in contrast to our earlier erroneous deduction. Moreover, the knowledge of the absolute configuration at the phosphorus atom in both 4 (R = H, B = CBz) and 5 (R = Px, B = Thy) allows for assignment of the absolute configuration at phosphorus in precursors of 4‘ and 5, such as 5‘-O-DMT-nucleoside 3‘-O- methanephosphonothioanilidates (6), methanephosphonoanilidates (8), and methanephosphonoselenoanilidates (9).