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

✍ Scribed by Bai-Chuan Pan; Yung-Chi Cheng; Shih-Hsi Chu

• Publisher: Journal of Heterocyclic Chemistry
• Year: 1997
• Tongue: English
• Weight: 519 KB
• Volume: 34
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570340330

✦ Synopsis

Abstract

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__.