Synthesis and evaluation of a series of 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)thymines.
A series of 1-(3-alkyl-2,3-dideoxy-alpha,beta-D-erythro-pentofuranosyl)thymines (3'-alkyl-3'-deoxythymidines) has been prepared from 5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-D-glycero-pent-2- enono-1,4-lactone ((S)-5-[(tert-butyldiphenylsilyl)oxymethyl]-2(5H)- furanone) by Michael addition of the appropriate organocopper reagent, followed by reduction of the lactone, acetylation of the resulting hemiacetal, and trimethylsilyl triflate-catalyzed coupling with 2,4-di-O-(trimethylsilyl)thymine. The protected nucleosides were desilylated by using tetrabutylammonium fluoride to give anomeric mixtures of the free nucleosides. The unsubstituted 2',3'-dideoxynucleoside analog was similarly prepared from 5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-D-glycero-pentono- 1,4-lactone ((S)5-[(tert-butyldiphenylsilyl)-oxymethyl]-dihydro-2(3H)-fu r anone).
Agyei-Aye
K
K
Department of Chemistry, University of Alabama, Tuscaloosa 35487-0336.
Baker
D C
DC
D000107:Acetylation; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003300:Copper; D006678:HIV / Q000187:drug effects; D007783:Lactones; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D018139:Simplexvirus / Q000187:drug effects; D013936:Thymidine / Q000138:chemical synthesis* / Q000494:pharmacology; D013941:Thymine / Q000031:analogs & derivatives*; D014297:Trimethylsilyl Compounds
D007783:Lactones; D014297:Trimethylsilyl Compounds; D003300:Copper; D013941:Thymine; D013936:Thymidine