Generated: May 26, 2017
|Title:||Method and compositions for the synthesis of BCH-189 and related compounds|
|Abstract:||The present invention relates to a method of preparing BCH-189 and various analogs of BCH-189 from inexpensive precursors with the option of introducing functionality as needed. This synthetic route allows the stereoselective preparation of the biologically active isomer of these compounds, .beta.-BCH-189 and related compounds. Furthermore, the steochemistry at the nucleoside 4' position can be controlled to produce enantiomerically-enriched .beta.-BCH-189 and its analogs.|
|Inventor(s):||Liotta; Dennis C. (Stone Mountain, GA), Choi; Woo-Baeg (Atlanta, GA)|
|Assignee:||Emory University (Atlanta, GA)|
|Filing Date:||Feb 01, 1990|
|Claims:||1. A method of preparing a composition comprising predominantly the .beta.-isomer of a 1,3-oxathiolane of the structure: ##STR8## wherein R' is an acyl group, and wherein R is an oxygen-protecting group with silylated cytosine in the presence of SnCl.sub.4. |
2. The method of claim 1, wherein R is selected from the group consisting of alkyl, silyl, and acyl.
3. The method of claim 1, further comprising the step of reacting a glycoaldehyde having the formula OHCCH.sub.2 OR, wherein R is a protecting group with thioglycolic acid to produce a 5-oxo-1,3-oxathiolane.
4. The method of claim 3 further comprising:
(i) reducing the oxo group in 5-oxo-1,3-oxathiolane to an alcohol; and
(ii) acylating the alcohol.
5. The method of claim 4, wherein the reducing agent is selected from the group consisting of diisobutylaluminum hydride, sodium bis(2-methoxyethoxy)aluminum hydride, and NaBH.sub.4.
6. The method of claim 1, further comprising replacing R with hydrogen.
7. The method of claim 6, wherein R is an acyl group, and wherein the acyl group is removed with sodium methoxide.
8. The method of claim 1, wherein the composition consists essentially of the .beta.-isomer of 2',3'-dideoxy-3'-thiacytidine.
9. The method of claim 1, wherein R is a silyl group, and wherein the silyl group is removed with (n--C.sub.4 H.sub.9).sub.4 NF.
10. The method of claim 2, wherein the silyl group is t-butyldiphenylsilyl.
11. The method of claim 2, wherein the silyl group has the formula ##STR9## wherein R.sub.1, R.sub.2, and R.sub.3 are independently C.sub.1 to C.sub.5 alkyl or phenyl.