Numata M, Sugimoto M, Ito Y, Ogawa T
Central Research Institute, Saitama, Japan.
Carbohydr Res. 1990 Aug 15;203(2):205-17. doi: 10.1016/0008-6215(90)80018-x.
An efficiently stereocontrolled total synthesis of GM3 alpha-D-Neup5Ac-(2----3)-beta-D-Galp-(1----4)-beta-D-Glcp-(1----1) -Cer was achieved by employing both methyl 5-acetamido-4,7,8,9-tetra-O-benzyl-2-bromo-2,3,5-trideoxy-3- phenylthio-D-erythro-beta-L-gluco-2-nonulopyranosonate for the key sialylation step, and O-[methyl(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha -D-galacto-2-nonulopyranosyl)onate]-(2----3)-O-(2,4,6-tri-O- acetyl-beta-D-galactopyranosyl-(1----4)-3,6-di-O-acetyl-2-O-pivaloyl- alpha-D-glucopyranosyl trichloroacetimidate and fluoride for the key coupling step with a ceramide derivative. These two steps were significantly altered and improved in comparison with our previous synthesis that had been executed without use of stereocontrolling auxiliaries. GM3 was obtained in 4.5% overall yield in 19 steps starting from allyl O-(2,6-di-O-acetyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-(1----4 )-2,3,6-tri-O-acetyl-beta-D-glucopyranoside.
通过使用5-乙酰氨基-4,7,8,9-四-O-苄基-2-溴-2,3,5-三脱氧-3-苯硫基-D-赤藓糖-β-L-葡萄糖-2-壬糖酸甲酯进行关键的唾液酸化步骤，以及O-[甲基(5-乙酰氨基-4,7,8,9-四-O-乙酰基-3,5-二脱氧-D-甘油-α-D-半乳糖-2-壬糖酸基)酯]-(2→3)-O-(2,4,6-三-O-乙酰基-β-D-吡喃半乳糖基-(1→4)-3,6-二-O-乙酰基-2-O-新戊酰基-α-D-吡喃葡萄糖基三氯乙酰胺和氟化物进行与神经酰胺衍生物的关键偶联步骤，实现了GM3α-D-Neup5Ac-(2→3)-β-D-Galp-(1→4)-β-D-Glcp-(1→1)-Cer的高效立体控制全合成。与我们之前未使用立体控制助剂进行的合成相比，这两个步骤有了显著改变和改进。从烯丙基O-(2,6-二-O-乙酰基-3,4-O-异亚丙基-β-D-吡喃半乳糖基)-(1→4)-2,3,6-三-O-乙酰基-β-D-吡喃葡萄糖苷开始，经19步反应，以4.5%的总收率得到了GM3。
