Stereoselective synthesis of 2'-beta-carbon-substituted 2'-deoxy-4'-thioribonucleosides from 4-thiofuranoid glycal.
The 4-thiofuranoid glycal 6 was converted into 1-chlorinated derivative 7 through LDA lithiation. When 7 was treated with LTMP, successful C-2 lithiation occurred, and subsequent treatment of the lithiated species with MeI gave 8. Dechlorination of 8 with Na/liq.NH3 yielded the 2-methyl glycal 9. Glycosidation of 9 with silylated thymine was mediated with PhSeCl as an electrophile, and gave the beta-isomer 10 stereoselectively. Removal of the 2'-phenylselenenyl group of 10 was effected with tributyltin radical, and subsequent deprotection furnished the target 2'-beta-methyl 4'-thiothymidine (11). In a similar manner, the corresponding cytosine analogue 12 could also be synthesized.
D002244:Carbon / Q000737:chemistry*; D012263:Ribonucleosides / Q000138:chemical synthesis*; D012833:Siloxanes / Q000737:chemistry*; D013876:Thiophenes / Q000737:chemistry*
C476353:4-thiofuranoid glycal; D012263:Ribonucleosides; D012833:Siloxanes; D013876:Thiophenes; D002244:Carbon