Synthesis and γ‐radiolysis of 2′‐deoxy‐5‐fluorouridine and 5‐fluorouridine derivatives

Abstract

Seventeen compounds having a variety of substituents at the 3‐ and 5′‐positions of 2′‐deoxy‐5‐fluorouridine (5‐FUdR) and 5‐fluorouridine (5‐FUR) were synthesized, and their γ‐radiolysis in aqueous solutions were studied. The compounds having thioureido (RNHCSNH, R  H, PhCH2, acyl) and thiocarbonylamino (XCSNH, X  PhCH2S, PhO) groups at the 3‐position of 5‐FUdR were efficiently cleaved to give 5‐FUdR with high G values upon γ‐irradiation of their aqueous solutions. The active species for these cleavage reactions were hydrated electron (e− aq), H• and HO•. However, the compounds having a dimethylsulfoxyimino group at 3‐position of 5‐FUdR and 5‐FUR afforded 5‐FUdR and 5‐FUR only under the radiolysis conditions where e− aq becomes a principal active species. The compound having a 2‐benzoylthiazoylthiocarbonylamino group at the 3‐position of 5‐FUdR showed the highest reactivity toward HO.. The mechanisms of these γ‐radiolysis reactions are discussed. The examination of anticellular activities of γ‐irradiated compounds having a thiocarbonylamino group at the 3‐position of 5‐FUdR toward murine Sarcoma 180 cells revealed that these compounds may be utilized as a candidate for a radiation‐induced drug (RID).

Sulfoximines: Structures, Properties and Synthetic Applications

“…302 Within the concept of "radiation induced drugs" Kuroda et al considered the synthesis of the sulfoximine substituted 2'-deoxy-5-fluorouridine and 5-fluorouridine 553. 303 Chemists of the Marion Merril Dow Research Institute synthesised a number of dialkyl sulfoximines of type 554 as myristic acid analogues. 304 They were found to inhibit biological processes that are dependent on a myristoylation event.…”