Baumann H, Scheen H, Huppertz B, Keller R
Macromolecular Chemistry and Textile Chemistry, RWTH Aachen, Germany.
Carbohydr Res. 1998 Jun;308(3-4):381-8. doi: 10.1016/s0008-6215(98)00097-4.
The degree of completeness and selectivity of the solvolytic O-6-desulfation reactions of the glucosamine moiety adjacent to the 2-O-sulfoiduronic acid group of heparin was systematically studied. Using solutions of various ammonium salts of heparin (salts of tributylamine, quinoline and pyridine) in mixtures of 9:1 aprotic solvents and water (solvents of medium polarity, in order of decreasing polarity: Me2SO > Me2NCHO > Me2NAc > N-methylpyrrolidinone), the influence of different reaction conditions were studied. The ammonium salt of heparin with a strong base (e.g., tributylamine) in Me2SO showed almost no desulfation, while in Me2NCHO a relatively low degree of completeness of O-6-desulfation (30%) with moderate selectivity (15% [I-2(OS)]-desulfation) was observed. Weak bases like quinoline or pyridine in Me2SO-water resulted in nearly complete [A-6(OS)]-desulfation (95 and 94%, respectively) with low selectivity [I-2(OS)]-desulfation (49 and 35%, respectively). The heparin pyridinium salt in Me2NCHO-water showed both a relatively high degree of completeness and high selectivity (72% [A-6(OS)]- and 8% [I-2(OS)]-desulfation). The highest regioselectivity (i.e., a high degree of completeness accompanied by high selectivity) was achieved using an N-methylpyrrolidinone-water mixture (88% [A-6(OS)]-desulfation and 10% [I-2(OS)]-desulfation). A nearly complete O-6-desulfation (95%), accompanied by a lower selectivity (18% [I-2(OS)]-desulfation), was achieved when the reaction was carried out twice. Lower temperature improved selectivity (5% [I-2(OS)]-desulfation) but reduced the completeness of [A-6(OS)]-desulfation (72%). In comparison with the variety of O-6-desulfations reported to date, the novel reactions presented in this article led to remarkable increase in completeness and regioselectivity of the reactions that were investigated.
对与肝素的2-O-硫酸化艾杜糖醛酸基团相邻的氨基葡萄糖部分的溶剂解O-6-脱硫反应的完整性和选择性程度进行了系统研究。使用肝素的各种铵盐（三丁胺盐、喹啉盐和吡啶盐）在9:1的非质子溶剂与水的混合物（中等极性溶剂，按极性降低顺序排列：二甲基亚砜>二甲基甲酰胺>二甲基乙酰胺> N-甲基吡咯烷酮）中，研究了不同反应条件的影响。肝素与强碱（如三丁胺）形成的铵盐在二甲基亚砜中几乎没有脱硫现象，而在二甲基甲酰胺中观察到O-6-脱硫的相对较低的完整性程度（30%）和中等选择性（15% [I-2(OS)]-脱硫）。像喹啉或吡啶这样的弱碱在二甲基亚砜-水体系中导致几乎完全的[A-6(OS)]-脱硫（分别为95%和94%），但选择性较低的[I-2(OS)]-脱硫（分别为49%和35%）。肝素吡啶盐在二甲基甲酰胺-水体系中显示出相对较高的完整性程度和高选择性（72% [A-6(OS)]-脱硫和8% [I-2(OS)]-脱硫）。使用N-甲基吡咯烷酮-水混合物实现了最高的区域选择性（即高完整性程度伴随着高选择性）（88% [A-6(OS)]-脱硫和10% [I-2(OS)]-脱硫）。当反应进行两次时，实现了几乎完全的O-6-脱硫（95%），但选择性较低（18% [I-2(OS)]-脱硫）。较低的温度提高了选择性（5% [I-2(OS)]-脱硫），但降低了[A-6(OS)]-脱硫的完整性程度（72%）。与迄今为止报道的各种O-6-脱硫反应相比，本文中提出的新反应导致所研究反应的完整性和区域选择性显著提高。
