Carbohydrate Research 315 (1999) 339 – 344 Note An easy stereospecific synthesis of 1-amino-2,5-anhydro-1-deoxy-D-mannitol and arylamino derivatives Samantha Claustre a , Fre ´de ´ric Bringaud b , Laurent Aze ´ma a , Rudi Baron a , Jacques Pe ´rie ´ a , Miche `le Willson a, * a Groupe de Chimie Organique Biologique, UMR CNRS 5623, Uniersite ´ Paul Sabatier, F -31062 Toulouse, France b Laboratoire d’Immunologie et Biologie Mole ´culaire de Parasites Protozoaires, UPRESA CNRS 5016, Uniersite ´ de Bordeaux II, F -33076 Bordeaux, France Received 5 January 1998; revised 29 January 1999; accepted 29 January 1999 Abstract 1-Amino-2,5-anhydro-1-deoxy-D-mannitol and a series of arylamino derivatives were prepared by nitrous acid deamination of 2-amino-2-deoxy-D-glucose and subsequent reductive amination of the resulting 2,5-anhydro-D-man- nose. Some of these compounds showed an enhanced affinity for the hexose transporter of Trypanosoma brucei as compared to D-fructose. © 1999 Elsevier Science Ltd. All rights reserved. Keywords: 1-Amino-2,5-anhydro-1-deoxy-D-mannitol; 2,5-Anhydro-1-arylamino-1-deoxy-D-mannitol derivatives; Trypanosoma brucei hexoses transporter (THT1) 1. Introduction In the course of a programme devoted to glycolytic enzymes inhibitors and D-glucose intake in the trypanosome [1], we became interested in the synthesis of D-fructose ana- logues [2] for the following reasons: (i) the hexose transporter of Trypanosoma brucei (THT1) recognizes not only D-glucose but also D-fructose, whereas that of human erythrocyte has only affinity for D-glucose [3,4]. Because of this peculiarity, one can consider the possi- bility of the specific intake of active com- pounds into the parasite via the transporter by binding such active compounds to a D-fruc- tose unit, or to the analogue of -D-fructose, 2,5-anhydro-D-mannitol, which also has a sig- nificant affinity for the hexose transporter THT1 [3,4]. Bringaud and Baltz [5,6] have shown that genes encoding for this transporter were highly conserved among kinetoplastidae, a feature which underlines the importance of this protein as a target for chemotherapy of trypanomiasis (sleeping sickness). These au- thors have also shown that these transporters are different in structure from that of the erythrocyte GLUT1 as revealed by a distinct sensitivity towards classical inhibitors; (ii) three of the enzymes of the glycolytic cascade, phosphoglucoisomerase, phosphofructokinase and aldolase, involve a phosphorylated fruc- tose as substrate or product. In addition, the * Corresponding author. Fax: +33-5-561-251733. E -mail address: willson@iris.ups-tlse.fr (M. Willson) 0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PII:S0008-6215(99)00040-3