Phosphate-Catalyzed Degradation of d-Glucosone in Aqueous Solution Is Accompanied by C1–C2 Transposition

Abstract

Pathways in the degradation of the C(6) 1,2-dicarbonyl sugar (osone) D-glucosone 2 (D-arabino-hexos-2-ulose) in aqueous phosphate buffer at pH 7.5 and 37 °C have been investigated by (13)C and (1)H NMR spectroscopy with the use of singly and doubly (13)C-labeled isotopomers of 2. Unlike its 3-deoxy analogue, 3-deoxy-D-glucosone (3-deoxy-D-erythro-hexos-2-ulose) (1), 2 does not degrade via a 1,2-hydrogen shift mechanism but instead initially undergoes C1-C2 bond cleavage to yield d-ribulose 3 and formate. The latter bond cleavage occurs via a 1,3-dicarbonyl intermediate initially produced by enolization at C3 of 2. However, a careful monitoring of the fates of the sketetal carbons of 2 during its conversion to 3 revealed unexpectedly that C1-C2 bond cleavage is accompanied by C1-C2 transposition in about 1 out of every 10 transformations. Furthermore, the degradation of 2 is catalyzed by inorganic phosphate (P(i)), and by the P(i)-surrogate, arsenate. C1-C2 transposition was also observed during the degradation of the C(5) osone, D-xylosone (D-threo-pentose-2-ulose), showing that this transposition may be a common feature in the breakdown of 1,2-dicarbonyl sugars bearing an hydroxyl group at C3. Mechanisms involving the reversible formation of phosphate adducts to 2 are proposed to explain the mode of P(i) catalysis and the C1-C2 transposition. These findings suggest that the breakdown of 2 in vivo is probably catalyzed by P(i) and likely involves C1-C2 transposition.