Nakano T, Ito Y, Ogawa T
Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Carbohydr Res. 1993 Apr 23;243(1):43-69. doi: 10.1016/0008-6215(93)84080-p.
The sulfated glucuronyl glycosphingolipids isolated from the human peripheral nervous system, HO3S-3-beta-GlcpA-(1-->3)-[beta-D-Galp-(1-->4)-beta-D-GlcpNA c-(1-->3)]n- beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->1)-Cer (n = 1, 2) (1 and 2) were synthesized. The glycan part of target molecules was designed to be constructed from glucuronate, lactosamine, and lactose fragments 8, 9 (or 10), and 11, which in turn were synthesized stereo- and/or regio-selectively from readily available compounds. The coupling reaction between 9 and 11 was performed by the action of trimethylsilyl trifluoromethanesulfonate (Me3SiOTf)), and subsequent manipulation of product 31 gave 33. On the other hand, slight modification of this sequence, including repetitive glycosylation reactions using 10, afforded hexasaccharide 46. These compounds were reacted with nonreducing end glucuronate synthon 8 under the agency of CuBr2-AgOTf-Bu4NBr, and the resultant penta- and hepta-saccharides 34 and 47, respectively, were transformed into glycosyl fluorides. Final coupling with the ceramide derivative 7, followed by chemoselective deprotection of the levulinoyl group, sulfation and complete deprotection, afforded the target glycolipids 1 and 2.
从人外周神经系统分离得到的硫酸化葡糖醛酸基糖鞘脂HO3S-3-β-GlcpA-(1→3)-[β-D-Galp-(1→4)-β-D-GlcpNAc-(1→3)]n-β-D-Galp-(1→4)-β-D-Glcp-(1→1)-Cer（n = 1, 2）（1和2）被合成出来。目标分子的聚糖部分设计为由葡糖醛酸、乳糖胺以及乳糖片段8、9（或10）和11构建而成，这些片段又分别从易得的化合物立体选择性和/或区域选择性地合成。9和11之间的偶联反应通过三甲基甲硅烷基三氟甲磺酸酯（Me3SiOTf）作用进行，产物31随后经处理得到33。另一方面，对该序列进行轻微修饰，包括使用10进行重复糖基化反应，得到六糖46。这些化合物在CuBr2-AgOTf-Bu4NBr作用下与非还原端葡糖醛酸合成子8反应，分别得到的五糖和七糖34和47被转化为糖基氟化物。最后与神经酰胺衍生物7偶联，随后对乙酰丙酸酰基进行化学选择性脱保护、硫酸化并完全脱保护，得到目标糖脂1和2。
