An eficient and short synthesis of enantiomericolly pure (+)-BCH-189 has been accomplished from D-galactose via 1,6-thioonhydro-Dgalacto~.
Belleau and coworkers1 reported the synthesis and anti-HIV activity of an unusual class of nucleosides, (*)-dioxolane-thymine and (k)-BCH-189 in which C-3' positions of these nucleosides have been replaced by oxygen and sulfur atom, respectively. Norbeck et al? also reported the synthesis of (k)-dioxolane-thymine which was found to exhibit a moderate anti-HIV activity. Thus, it was of interest to synthesize an enantiomerically pure isomer of (f)-dioxolane-thymine.
Recently, we have reported asymmetric synthesis of (-)dioxolane-thymine from 1,6-anhydro-D-mannose as a chiral template.3 We found that the enantiomerically pure isomer was a potent anti-HIV agent in human peripheral blood mononuclear (PBM) cells. However, it was found that the (-)-isomer was somewhat less potent than the racemic mixture. The implication of this difference in activity is under investigation.
Since BCH-1X9 is expected to undergo clinical trials in patients with AIDS and AIDS-related complex, it was of interest to synthesize the enantiomerically pure isomer of BCH-189. Recently, we have completed the synthesis of (+)-BCH-189 from D-mannose in 20 steps via 1,~thioanhydro-D-mannose. Although the procedure resulted in an enantiomerically pure form of (+)-BCH-189, the synthetic steps were tot lengthy and the overall yield was not sufficiently high enough for large scale synthesis.
Thus, we wish to report more efficient and shorter synthetic route to (+)-BCH-189 from 1,6thioanhydro-D-galactose
(1)5 (scheme l).The preparation of 1 was more straightforward and gave excellent yield, compared to that of 1,6-thioanhydro-D-manose. Furthermore, all intermediates during the preparation of