Synthesis of racemic and enantiomerically pure 2′‐thia‐2′,3′‐dideoxycytidine as potential anti‐hepatitis B virus agents

A novel class of nucleosides with the C 1 , atom bonded to three hetero atoms was synthesized. 2′‐Thia‐2′,3′‐dideoxycytidine was the pilot compound of this series. (±)‐β‐2′‐Thia‐1′,3′‐dideoxycytidine ( 6 ) and (±)‐α‐2′‐thia‐2′,3′‐dideoxycytidine ( 7 ) were synthesized from (±)‐3‐mercapto‐1,2‐propanediol. The synthesis of the enantiomerically pure 2′‐thia‐2′,3′‐dideoxycytidines (α‐D‐form, β‐D‐form, α‐1‐form and β‐L‐form) from optically pure ( S )‐(2,2‐dimethyl‐1,3‐dioxalan‐yl)methyl p ‐toluenesulfonate ( 8 ) and its ( R )‐isomer 18 was also described. The preliminary biological results showed that (+)‐β‐D‐2′‐thia‐2′,3′‐dideoxycytidine ( 26 ) was the most active against human hepatitis B virus with an ED 50 of 3 μ M .