Design, Synthesis, and Antioxidant/Antidiabetic Activity of Nucleic Acid Bases Bearing FusedN,S-Heterocyclic Phosphor Esters

Abstract

Reactions of unsaturated and saturated Wadsworth–Horner–Emmons reactants with N1‐ and N3‐allyl‐2‐thiouracils, under phase‐transfer catalysis conditions, resulted in the respective N‐bridged thiazolo‐, pyrrolo‐, and thiazino‐phosphor esters. Products were obtained via the regioselective attack of the Wadsworth–Horner–Emmons reagent on the allylic‐1′‐C in tandem of double bond migration processes, followed by a series of transformations. Synthesis of pyrimidin‐1(2H, or 6H)‐yl)but‐1‐ene‐1,1‐diyldiphosphonates was also described. On the basis of the prediction results (PASS program, Moscow, Russia; free available internet version of PASS 2009.1: http://http://www.ibmc.msk.ru/PASS), we further estimated the antioxidant and antidiabetic activities of the synthesized compounds. The results showed that all compounds cause moderate to good antidiabetic activities. However, the thiazolophosphonates exhibited the highest inhibitory antioxidant activity; nevertheless, the diphosphonates manifested the best protective effects against DNA damage induced by bleomycin. Biological testing confirmed the results of computational modeling.

Functional bisphosphonate synthesis for the development of new anti-resorption bone drug candidates

“…Upon reaction of MBP with N 1 -and N 3 -allyl-2-thiouracils under phase-transfer catalysis conditions, the products reported in Scheme 2D and E were obtained. 30 A useful synthetic route for the formation of enamino keto esters which use nitriles and ethyl acetoacetate has been reported recently by Pei and collaborators (Scheme 2F). 31…”