Synthetic Study of Sulfatides

硫脂的生理作用目前尚不清楚。它们是属于鞘氨醇-糖脂的化合物，其特征是分子中含有非常极性的磺酸部分。硫脂通常是几种化合物的混合物。硫脂的这种结构复杂性是由于其脂类部分神经酰胺的复杂性，神经酰胺由称为鞘氨醇的碱和一种酸组成。后者都是不同碳链长度的化合物的混合物。因此，硫脂的复杂性主要归因于鞘氨醇和酸性部分。为了合成化学纯的硫脂，因此合成化学纯的鞘氨醇是必要的。这是硫脂合成中的一个问题。硫脂合成中的另一个问题是在糖(即半乳糖)中区域选择性地引入一个磺酸基团。本研究针对这两个问题进行了研究，并阐明了以下几点：(1)开发了一种通过糖苷区域选择性单氧化合成氨基糖的新方法。从而建立了以易得的木糖或葡萄糖为原料合成氨基糖的实用方法。应用这种新方法，以较低的成本合成了抗生素诺吉霉素，这是一种著名的葡萄糖苷酶抑制剂。(2)将上述方法得到的4-氨基-4-脱氧阿拉伯糖转化为合成各种鞘氨醇的“手性共同中间体”。用该中间体合成了C-18鞘氨醇。(3)在半乳糖部分引入磺酸基：用二丁基氧化锡和氯磺酸将β-半乳糖苷衍生物区域选择性地硫化得到3-磺酸衍生物。(4)用光度离子色层(PIC)对糖磺酸酯进行了分析。这是将高效液相色谱应用于这种高极性且不能吸收紫外线的化合物的一个例子。

The physiological role of sulfatides is not clear at present. They are the compounds grouped to sphingo-glycolipids, and are characterised in having very polar sulfonic acid moiety in the molecule. Usually sulfatide is obtained as a mixture of seversal compounds. This structural complexity of sulfatide is due to the complexity of its lipid part, ceramide, which is constitued of a base, called sphingosine, and an acid. Both of the latters are the mixtures of the compounds of various carbon chain length. Therefore, the complexity of sulfatide is mainly attributable to that of sphinogosine and the acid part. In order to synthesize chemically pure sulfatide, it is therefore necessary to sythesize chemically pure sphingosine. This is one problem in sulfatide synthesis.Another problem in sulfatide synthesis is the regio-selective introduction of a sulfonic acid group in the sugar (i.e.,galactose)portion.The present study was done for solving these two problems, and clarified the followings:(1) A new method of regio- and stereo-selective synthesis of amino-sugars via regioselective mono-oxidation of glycosides was exploited. Thus, the method of practical synthesis of aminosugars from easily available xylose or glucose was established. By application of this new method, an antibiotic, nojirimycin, a famous glucosidase inhibitor, was synthesised economically.(2) 4-Amino-4-deoxy-arabinose obtained by the above method was converted to a "chiral common intermediate" to various sphingosines. Synthesis of C-18 sphingosine from this intermediate was described.(3) Regioselective introduction of sulfonic acid group into the galactose portion: Sulfatation of beta-galactoside derivatives by dibutyltin oxide and chlorsulfonic acid gave 3-sulfonic acid derivatives regioselectively.(4) Sugar sulfonic acid esters were well analysed by using photometric ion chromatography (PIC). This is an example of application of HPLC to such highly polar and not UV absorbale compounds.