Synthesis of biurets via TMSNCO addition to 1-aminosugars: application in the de novo synthesis of dC oxidation products.

The reaction between 1-aminosugars and trimethylisocyanate (TMSNCO) was optimised as a one-step synthetic strategy for the synthesis of sugar biurets. This protocol was successfully applied to a number of 1-aminosugars, which exclusively provided the corresponding biurets in 67-99% yields. The new methodology was applied in the de novo synthesis of N1-(2-deoxy-α/β-d-erythro-pentofuranosyl)biuret (dfBU) and N1-(2-deoxy-α/β-d-erythro-pentopyranosyl)biuret (dpBU), two known DNA lesions arising from the hydroxyl radical induced decomposition of 2'-deoxycytidine (dCyd).

First characterisation of two important postulated intermediates in the formation of a HydT DNA lesion, a thymidine oxidation product.

A number of environmental pollutants and endogenous oxidation agents form 1-(2-deoxy-β-d-ribofuranosyl)-5-hydroxy-5-methylhydantoin (HydT), an important DNA lesion resulting from thymidine oxidation. In this paper, two intermediates, postulated in the formation of HydT, have been characterised for the first time. The first, N1-formyl-N3-pyruvoylurea intermediate, was produced by the ozonolysis reaction of 2',3',5'-tri-O-acetylribo-, 3',5'-di-O-TBS- and N3,O3',O5-tribenzyl-protected thymidines and was shown to produce, upon decomposition and depending on the protecting group and the conditions, HydT alone, or together with protected-β-d-ribofuranosyl-N1-formylurea and formamide products.