Synthesis of 4,6-dideoxysucrose, and inhibition studies of leuconostoc and streptococcusd-glucansucrases with deoxy and chloro derivatives of sucrose modified at carbon atoms 3, 4, and 6

Abstract

Starting from sucrose, 2,3,1′,3′,4′,6′-hexa- O-benzoyl-6-deoxy-6-iodosucrose 1 ( 1) was synthesized. Reaction of 1 with sulfuryl chloride in pyridine gave 2,3,1′,3′,4′,6′-hexa- O-benzoyl-4-chloro-4,6-dideoxy-6-iodogalactosucrose ( 2). Compound 2 was treated with tributyltin hydride in toluene in the presence of a radical initiator, α,α-azobis(isobutanonitrile) (AIBN), to remove iodine and chlorine groups and give hexa- O-benzoyl-4,6-dideoxysucrose. Benzoyl groups were removed by sodium methoxide in methanol to give 4,6-dideoxysucrose. Sucrose was modified at carbon atom 3, carbon atom 4, or carbon atoms 4 and 6, and these analogs were tested as inhibitors of the d-glucansucrases ( d-glucosyltransferases) of Streptococcus mutans 6715 and Leuconostoc mesenteroides B-512F. Sucrose analogs used in this study are 4-deoxysucrose and 4-chloro-4-deoxygalactosucrose with S. mutans 6715 d-glucansucrases (GTF-S and GTF-I), and 3-deoxysucrose, 4-deoxysucrose, 4-chloro-4-deoxygalactosucrose, 6-deoxysucrose, and 4,6-dideoxysucrose with L. mesenteroides B-512F d-glucansucrase. The data indicate that 3-deoxysucrose, 4-deoxysucrose, and 4-chloro-4-deoxygalactosucrose are weak noncompetitive inhibitors for B-512F dextransucrase, with K i values of 530, 201, and 202m m respectively. For the same enzyme, 6-deoxysucrose was a strong competitive inhibitor, with K i of 1.60m m, and 4,6-dideoxysucrose was a good competitive inhibitor, with K i of 20.3m m. 4-Deoxysucrose was a weak noncompetitive inhibitor for both GTF-I and GTF-S, with K i values of 672 and 608m m, respectively. 4-Chloro-4-deoxygalactosucrose was also a weak non-competitive inhibitor for GTF-I and GTF-S with K i values of 391 and 308m m, respectively. The inhibition data indicate that replacement of the 6-hydroxyl group by a hydrogen atom results in a strong competitive inhibitor, and that the hydroxyl groups at C-3 and C-4 are important in the binding of sucrose to the active sites of d-glucansucrases.