CHEMICAL SYNTHESIS OF MENINGOCOCCAL GROUP A OLIGOSACCHARIDES

控制大小的寡糖的合成正在进行中， 以提供用于制备缀合物的材料。 这些 缀合物将使得有可能确定 寡糖大小对缀合物疫苗免疫原性的影响。一个 制备了合适的固相载体。这种支持 结合了一个四碳间隔臂，该间隔臂通过以下方式连接到支架上： 可选择性裂解的二硫键。已经发现， 带有浓度为50毫摩尔/克的可衍生基团。这是 确定常规的b-氰乙基保护的亚磷酸化 试剂，需要完成活化单体的合成， 对于该合成不是最佳的，因此苄基保护的 制备亚磷酸化试剂。该试剂是优选的，因为 它使用与已经存在于 单体的碳水化合物部分。与第二次世界大战的情况相反， b-氰乙基保护的中间体， 苄基保护的中间体copurify的α-端基。 这使得 异头物的基本分离少得多的劳动密集型。 所需的 单体，2-乙酰氨基-3-O-乙酰基-4-O-苄基-2-脱氧-6- 芴基甲氧基羰基-α-D-吡喃甘露糖基-N， N-二异丙基-O-苄基-亚磷酰胺，制备、纯化并 表征了该单体已用于制备 四糖附着在固相上。 耦合测量 效率表明，合成可以很容易地扩展到 产生20聚体。目前正在进行有效清除 从支持物中除去糖。

The synthesis of controlled size oligosaccharides is being pursued in order to provide material for the preparation of conjugates. These conjugates will make it possible to determine the effects of oligosaccharide size on immunogenicity of a conjugate vaccine. An appropriate solid phase support has been prepared. This support incorporates a four-carbon spacer arm which is attached to the support by a selectively cleavable disulfide bond. The support has been found to bear derivatizable groups at a concentration of 50 mmoles/gm. It was determined that the conventional b-cyanoethyl protected phosphitylating reagent, required to complete the synthesis of the activated monomer, would not be optimal for this synthesis, therefore a benzyl protected phosphitylating reagent was prepared. This reagent was preferable because it uses the same protective group as is already present in the carbohydrate moiety of the monomer. In contrast to the case of the b-cyanoethyl protected intermediate, the phosphite enantiomers of the a-anome of the benzyl protected intermediate copurify. This makes the essential separation of anomers much less labor intensive. The required monomer, 2-acetamido-3-0-acetyl-4-0-benzyl-2-deoxy-6- fluorenylmethoxycarbonyl-a-D-mannopyranosyl-N, N-diisopropy-0-benzyl-phosphoramidite, was prepared, purified and characterized. This monomer has been used to prepare a tetrasaccharide attached to the solid phase. Measurement of coupling efficiency indicated that the synthesis can be readily extended to produce a 20-mer. Work is now progressing on the efficient removal of the saccharide from the support.