Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions

Abstract

For the synthesis of y 1-(3′-deoxy-β-D- glycero-pentofuran-2′-ulosyl)uracil ( 16), the precursor, 5′-O-benzoyl derivative ( 2), 2 was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil ( 4) 2 was benzoylated to N 3-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil ( 8) and its 3′,5′-O-isopropylidene analog ( 10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil ( 11) was first benzoylated to give 2′,5′-di-O-benzoate ( 12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product ( 12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil ( 15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.