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Poly-N-acetyllactosamine oligomer is a type-2 glycan core from which a number of important bioactive glycoconjugates are assembled in vivo. Development of an effective synthesis of N-acetyllactosamine oligomers will therefore provide a new chemoenzymatic entry to this class of complex saccharides. This paper describes the design and synthesis of thioglycoside building blocks, determination of their relative reactivity values, and demonstration of their use in the programmable one-pot synthesis of various N-acetyllactosamine oligomers. Through a combination of segment condensation, the strategy allows for the preparation of larger oligosaccharides with minimal protecting group manipulation, as illustrated in the synthesis of an octasaccharide in a very short period of time.

The total synthesis of the sialic acid-containing antigenic epitope fucose GM1 (Fuc-GM1) by an improved reactivity-based one-pot synthetic strategy is reported. Based on a thioglycoside reactivity database, three saccharide building blocks, 3, 4, and 5, were designed and prepared to incorporate a descending order of reactivity toward thiophilic activation. Using the reactivity-based one-pot synthetic method, the fully protected Fuc-GM1 glycoside 2 was furnished in a facile manner, which was globally deprotected to give the Fuc-GM1 glycoside 1. In addition, using the promoter system 1-(benzensulfinyl)piperidine͞trifluoromethanesulfonic anhydride, the product yield was improved and the reaction time was reduced in comparison with the N-iodosuccinimide͞trifluoro-methanesulfonic acid-and dimethyl (thiomethyl) sulfonium trifluoromethanesulfonate-promoted systems.synthetic vaccine F ucose GM 1 (Fuc-GM 1 ) ganglioside was first isolated from bovine thyroid tissue in 1979 (1). It is comprised of a hexasaccharide carbohydrate moiety and a ceramide-reducing end component. Within this carbohydrate framework is a tetrasaccharide (sugars a, b, d, and e) bearing a branched sialic acid residue (c) and a terminal fucose (f) (Fig. 1). It is found specifically in the tumor tissue of small-cell lung cancer (SCLC). SCLC accounts for 20% of lung cancer, which remains one of the leading causes of death in the United States (2). Unlike other cancer antigens, Fuc-GM 1 has a more restricted distribution in normal tissue, suggesting that this carbohydrate antigen may be a good target for active immunization. Development of an anti-(Fuc-GM 1 ) vaccine and mAb could potentially be of importance for diagnosis and immunotherapy of these tumors (3, 4). However, one of the barriers preventing effective production of an anticancer vaccine is the limited supply of chemically pure Fuc-GM 1 oligosaccharide. Despite the development of various oligosaccharide synthetic methods (5-8), the first synthesis of Fuc-GM 1 glycoside was reported by Allen and Danishefsky (9) two decades after its initial discovery. This elegant strategy incorporated the sulfonamide glycosidation method (10) in conjunction with a [3 ϩ 3] convergent glycosylation, ultimately leading to the target glycoside. It required protecting group and anomeric leaving group manipulations and encountered a problem with stereoselective formation of the ␤(1,4) glycosidic bond between a bulky trisaccharide donor and the poor nucleophilic trisaccharide acceptor.We envisioned that the incorporation of our programmable reactivity-based one-pot strategy (8) in the synthesis of the Fuc-GM 1 could simplify this complicated synthetic operation. In brief, the reactivity-based one-pot strategy is based on a developed competitive HPLC assay to assess quantitatively the reactivity of different thioglycosides, the so-called relative reactivity value (RRV). Such information is then used to guide the reactivity-based one-pot synthesis of an oligosaccharide without protecting group manipulation and intermed...

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Herein we describe an inhibition study of the sialyl Lewis x (sLe(x)) expression on a human monocytic cell line (U937), using a series of peracetylated N-Acetyllactosamine (LacNAc) analogues with variation at the aglycon moiety. It was found that the extent of inhibition was related to the hydrophobicity and structure of the aglycon. In general, peracetylated LacNAc analogues with a naphthyl or biphenyl aglycon (3, 4, 6, and 7) were better in suppression of sLe(x) expression than a benzyl derivative (2). Steady-state kinetic experiments with human alpha-1,3-fucosyltransferases IV and VI (FucT IV and VI, EC 2.4.1.65) revealed that the deacetylated LacNAc-aglycons with naphthyl (18, 19, and 20) or biphenyl (17) moieties exhibited higher affinity to the fucosyltransferases than aglycon moieties with smaller hydrophobic groups (14, 15, and 16). These results are in agreement with the findings of the U937 cell-based experiments, and suggest that the higher enzyme affinity LacNAc-aglycons make better acceptor decoys and, hence, the observed differences in LacNAc-aglycon inhihitory effects on sLe(x) expression.