Stereochemical transformations of 5′-amino-5′-deoxyuridine and its 5,6-dihydro-analogue. 5′-N-Aminoacyl derivatives of 5′-amino-5′-deoxy-5,6-dihydrouridine

Abstract

The synthesis of 5′-N-(N-t-butoxycarbonyl-glycyl)-(6), 5′-N-(N-t-butoxycarbonyl-L-phenylalanyl)-(7), and 5′-N-(N-benzyloxycarbonyl-L-phenylalanyl)-(8) derivatives of 5′-amino-5′-deoxy-2′,3′-O-isopropylidene-5,6-dihydrouridine by the active ester method is described. The 5′-N-(N-benzyloxycarbonyl-L-phenylalanyl-L-phenylalanyl) derivative (10) was built by elongation of the 5′-N-(L-phenylalanyl)-5,6-dihydrouridine unit (9).

The transformations of 5′-benzamido-5′-deoxy-2′,5′-dimethylsulphonyloxy-derivatives of uridine (20) and 5,6-dihydrouridine (21) in refluxing water afforded 2,2′-anhydro-1-(5-benzamido-5-deoxy-3-O-methylsulphonyl-β-D-arabinofuranosyl)uracil (22),1-(5-benzamido-5-deoxy-β-D-lyxofuranosyl)uracil (24), and 1-(5-benzamido-5-deoxy-3-O-methylsulphonyl-β-D-arabinofuranosyl)-5,6-dihydrouracil (25), respectively. On the other hand treatment of the 2′,3′-dimesyloxy-compounds (20) and (21) with potassium phthalimide in dioxan yielded selectively the corresponding 2,2′-anhydro-1-(5-benzamido-5-deoxy-3-O-methylsulphonyl-β-D-arabinofuranosyl)-uracil (22) and 5,6-dihydrouracil (23). 1-(5-Benzamido-5-deoxy-2,3-epoxy-β-D-lyxofuranosyl)uracil (27) was generated when 2′,3′-dimesyloxyuridine (20) was treated with aqueous sodium hydroxide.