Synthesis of sialyl Lewis X mimetic as an inhibitor of E-selectin mediated cellular adhesion and a new method for the in situ generation of anhydrous hydrogen iodide in an organic solvent and its use in synthetic reactions

The first step in the recruitment of leukocytes to the vascular wall in the immune response is mediated by a protein-carbohydrate recognition event. The leukocyte surface carbohydrate involved in this interaction is the tetrasaccharide glycoconjugate terminus, Neu5Acalpha(2 → 3)Galbeta(1 → 4)[Fucalpha(1 → 3)]GlcNAc, known as sialyl Lewis X (SLex). This work describes the synthesis and biological evaluation of SLex mimetic compound, 2-(trimethylsilyl)ethyl 3-O-carboxymethyl-beta- D-galactopyranosyl-(1 → 4)-[alpha-L-fucosyl(1 → 6)]-beta-D-glucopyranoside, from the readily available starting compound beta-D-lactose. The synthesis features the use of activated glycosylating agent, alpha-D-lactosyl iodide, prepared by the method developed in the course of this dissertation work (see, Part II); the regioselective derivatization at C-3' using a tin acetal intermediate; and the efficient construction of an alpha-(1 → 6) fucoside linkage. The silicon-tethered intramolecular radical cyclization approach for the construction of an alpha-C-fucoside compound is described, as are efforts toward the construction of the C-fucosyl linked analog of the SLex mimetic compound by the analogous method.; A new method for the in situ generation of anhydrous hydrogen iodide (HI) has been developed. This method involves the reaction of one mol equivalent of molecula iodine and two mol equivalents of thiolacetic acid in dry dicloromethane in the presence of a nucleophilic species to produce two mol equivalents of HI. The HI thus generated has been employed for the efficient preparation of alpha-glycosyl iodides and vicinal iodohydrins from the corresponding glycosyl acetates and epoxides, respectively, and for catalysis of Ferrier glycosylation.