Duclos R I
Department of Biophysics, Boston University School of Medicine, MA 02118-2526, USA.
Carbohydr Res. 2000 Oct 6;328(4):489-507. doi: 10.1016/s0008-6215(00)00121-x.
Previous syntheses of ganglioside GM3 (NeuAc alpha3Gal beta4Glc beta1Cer) are reviewed, and both chemoenzymatic and chemical total synthetic approaches were investigated. In a chemoenzymatic approach, (2S,3R,4E)-5'''-acetyl-alpha-neuraminyl-(2''' --> 3'')-beta-galactopyranosyl-(1'' --> 4')-beta-glucopyranosyl-(1' <--> 1)-2-azido-4-octadecene-1,3-diol (azidoGM3) was readily prepared utilizing recombinant beta-Gal-(1'' --> 3'/4')-GlcNAc alpha-(2''' --> 3'')-sialyltransferase enzyme, and was evaluated as a synthetic intermediate to ganglioside GM3. The chemical total synthesis of ganglioside GM3 was performed on one of the largest scales yet reported. The highlights of this synthesis include minimizing the steps necessary to prepare the lactosyl acceptor as a useful anomeric mixture, which was present in excess for the highly regioselective and fairly stereoselective sialylation with a known neuraminyl donor to give the protected GM3 trisaccharide. The synthetic methodology maximized convergence by a subsequent glycosidic coupling of the well-characterized GM3 trisaccharide trichloroacetimidate derivative with protected ceramide. The ganglioside GM3 was nearly homogeneous as the two glycosidic couplings utilized preparative HLPC purifications, and variations in the sphingosine base and fatty acyl group were under 0.1 and 0.2%, respectively.
本文综述了神经节苷脂GM3（NeuAcα3Galβ4Glcβ1Cer）以往的合成方法，并对化学酶法和化学全合成方法进行了研究。在化学酶法中，利用重组β - Gal - (1'' --> 3'/4') - GlcNAcα - (2''' --> 3'') - 唾液酸转移酶，很容易制备出(2S,3R,4E)-5'''-乙酰基-α-神经氨酰基-(2''' --> 3'')-β-吡喃半乳糖基-(1'' --> 4')-β-吡喃葡萄糖基-(1' <--> 1)-2-叠氮基-4-十八碳烯-1,3-二醇（叠氮基GM3），并将其作为神经节苷脂GM3的合成中间体进行了评估。神经节苷脂GM3的化学全合成是在迄今报道的最大规模之一上进行的。该合成的亮点包括将制备乳糖基受体所需的步骤减至最少，以得到有用的异头物混合物，该混合物在与已知的神经氨酰基供体进行高度区域选择性和相当立体选择性的唾液酸化反应时过量存在，以得到受保护的GM3三糖。合成方法通过将特征明确的GM3三糖三氯乙酰亚胺酯衍生物与受保护的神经酰胺进行后续糖苷偶联，最大限度地实现了汇聚。神经节苷脂GM3几乎是均匀的，因为两次糖苷偶联都使用了制备型高效液相色谱纯化，鞘氨醇碱基和脂肪酰基的变化分别在0.1%和0.2%以下。
