Barroca Nadine, Jacquinet Jean-Claude
Institut de Chimie Organique et Analytique, UFR Faculté des Sciences, UMR CNRS 6005, Université d'Orléans, BP 6759, F-45067 Orléans, France.
Carbohydr Res. 2002 Apr 17;337(8):673-89. doi: 10.1016/s0008-6215(02)00060-5.
The syntheses are reported for the first time of alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), its disulfated analogue alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc-(1-->4)-alpha-L-IdopA2SO(3)-(1-->OMe), and of beta-D-GalpNAc4SO(3)-(1-->4)-alpha-L-IdopA2SO(3)-(1-->3)-beta-D-GalpNAc4SO(3)-(1-->OMe), which represent structural fragments of dermatan sulfate, unavailable directly by chemical or enzymatic degradation of the glycosaminoglycan polymer. These molecules were readily obtained from a pair of key disaccharide intermediates, in which the relative difference of stability of the D-GalNAc 4-hydroxy protecting groups (acetate or pivalate) toward saponification conditions allowed access to various sulfoforms from a common precursor. For the preparation of these blocks, the 4-O-pivaloyl-D-galacto moiety was readily obtained through a one-pot stereospecific intramolecular nucleophilic displacement on an easily available 3-O-pivaloyl-D-gluco precursor, and the L-IdoA moiety through selective radical oxidation at C-6 of a L-ido 4,6-diol derivative with oxoammonium salts.
首次报道了α-L-艾杜糖醛酸2-硫酸酯-(1→3)-β-D-半乳糖胺4-硫酸酯-(1→4)-α-L-艾杜糖醛酸2-硫酸酯-(1→OMe)、其二硫酸化类似物α-L-艾杜糖醛酸2-硫酸酯-(1→3)-β-D-半乳糖胺-(1→4)-α-L-艾杜糖醛酸2-硫酸酯-(1→OMe)以及β-D-半乳糖胺4-硫酸酯-(1→4)-α-L-艾杜糖醛酸2-硫酸酯-(1→3)-β-D-半乳糖胺4-硫酸酯-(1→OMe)的合成，这些化合物代表硫酸皮肤素的结构片段，无法通过糖胺聚糖聚合物的化学或酶促降解直接获得。这些分子很容易从一对关键的二糖中间体获得，其中D-半乳糖胺4-羟基保护基（乙酸酯或新戊酸酯）对皂化条件的稳定性相对差异使得能够从一个共同的前体获得各种磺化形式。为了制备这些砌块，4-O-新戊酰基-D-半乳糖部分可通过在容易获得的3-O-新戊酰基-D-葡萄糖前体上进行一锅法立体定向分子内亲核取代反应轻松获得，而L-艾杜糖醛酸部分则可通过用氧鎓盐对L-艾杜糖4,6-二醇衍生物的C-6位进行选择性自由基氧化反应获得。
