Synthetic study of novel inositol phosphoceramide CJP2

新型神经节苷脂CJP2是由Higuchi等人从鸡冠花中分离得到的。这种神经节苷脂是独一无二的，因为它是一种含有唾液酸的肌醇磷酰胺衍生物；这种神经节苷脂以前没有被鉴定过。9-O-甲基-N-羟基神经氨基残基的存在在天然神经节苷脂中也是独一无二的。肌醇磷酰胺(IPC)存在于高等植物、酵母、真菌、一些细菌培养物和突变酵母中。虽然它们的内源功能还不是很清楚，但它们被认为可以保护植物组织免受坏死性病变的伤害，并被认为可以用于组织胞浆菌病的诊断。由于CJP2的可获得性有限，其生物活性仍不清楚。以D-葡萄糖为原料，采用立体选择性全合成的方法，研究了提供这类化合物的合成方法。IPC肌醇片段的合成是通过D-葡萄糖衍生的手性醛与乙烯基铜试剂的1，2-非对映选择性加成、Wittig亚甲基化、1，7-二烯的闭环歧化(RCM)和催化的非对映选择性OsO_4二氢羟基化反应来表征的。神经酰胺片段的合成参照Ogawa方法的改进步骤。以D-葡萄糖为原料合成了唾液酸衍生物糖基片段，作为唾液酸糖基供体的有效前体。合成的关键步骤是以1，7-二烯为原料，经RCM直接生成不饱和糖基，生成唾液酸乙醛衍生物。本合成提供了CJP2的肌醇片段、神经酰胺片段和唾液酸甘氨酸片段。这些片段的进一步功能基团转化和偶联将为CJP2及其相关类似物提供有价值的生物学评价。

The novel type ganglioside CJP2 has been obtained by Higuchi and co-workers from the feather star Comanthus japonica. This ganglioside is unique in that it is an inositolphosphoceramide derivative possessing sialic acid ; such ganglioside has not previously been identified. The presence of 9-O-methyl-N-glycolylneuraminosyl residue is also unique in naturally occurring gangliosides. Inositol phosphoceramide (IPC) is present in quite considerable quantities in higher plants, yeast, fungi, some bacterial cultures and mutant yeasts. Though their endogeinc functions are not well understood, but they are believed to protect plant tissues from necrotic lesions and are supposed to be applicable as test for the diagnosis of histoplasmosis. Because of limited availability of CJP2, their biological activity remains unknown. Development of the sufficient synthetic method to supply this class of compounds was investigated by stereoselective total synthesis from D-glucose. The synthesis of myo-inositol fragment of IPC is characterized by diastereoselective 1,2-addition of vinyl copper reagent to the chiral aldehyde derived from D-glucose, Wittig metbylenation, Ring-closing metathesis (RCM) of 1,7-diene and catalytic diastereoselective OsO4 dihydroXylation. The ceramide fragment was synthesized according to the modified procedure of Ogawa's method. The glycal fragment of sialc acid derivative as the useful precursor of glycosyl donor of sialic acid was also synthesized from D-glucose. The key step of this synthesis is the direct formation of unsaturated glycal moiety by RCM of 1,7-diene to produce sialic acid glycal derivative. The present synthesis provided myo-inositol fragment, ceramide fragment and sialic acid glycal fragment of CJP2. Further functional group transformation and coupling of these fragments will provide CJP2 and its related analogs valuable for biological evaluations.