Synthetic studies towards (−)-carba-3′-deoxy-3′-fluorothymidine.

Abstract

Stereospecific synthesis of (−)-carba-3′-deoxy-3′-fluorothymidine (−)- 11 is reported from the protected (−)-carbocyclic 3′-epi-thymidine (−)- 7 using diethylaminosulfur trifluoride. Under the conditions used, extensive dehydration of the blocked precursor into 10 and formation of the 4′-fluoro analogue ( 9 ) were also observed. An attempted simplification of our methodology based on (+)-(1R, 5S)-2-oxabicyclo[3.3.0]oct-6-en-3-one failed, but a novel cyclopentane ( 2 ) ring expansion to tetrahydropyran ( 18 ) was discovered.