Department of Materials Science and Engineering, Nagoya Institute of Technology, Nagoya, Japan.
Biomacromolecules. 2011 May 9;12(5):1449-59. doi: 10.1021/bm101328j. Epub 2011 Mar 30.
Poly(2'-deoxyadenosine) and poly(thymidine) constructed of carbonate linkages were synthesized by polycondensation between silyl ether and carbonylimidazolide at the 3'- and 5'-positions of the 2'-deoxyribonucleoside monomers. The N-benzoyl-2'-deoxyadenosine monomer afforded the corresponding polycarbonate together with the cyclic oligomers. However, the deprotection of the N-benzoyl group resulted in the scission of the polymer main chain. Thus, the N-unprotected 2'-deoxyadenosine monomers were examined for polycondensation. However, there was involved the undesired reaction between the adenine amino group and the carbonylimidazolide to form the carbamate linkage. In order to exclude this unfavorable reaction, dynamic protection was employed. Strong hydrogen bonding was used in place of the usual covalent bonding for reducing the nucleophilicity of the adenine amino group. Herein, 3',5'-O-diacylthymidines that form the complementary hydrogen bonding with the adenine amino group were added to the polymerization system of the N-unprotected 2'-deoxyadenosine monomer. Consequently, although the oligomers (M(n) = 1000-1500) were produced, the contents of the carbamate group were greatly reduced. The dynamic protection reagents were easily and quantitatively recovered as the MeOH soluble parts from the polymerization mixtures. In the polycondensation of the thymidine monomer, there tended to be involved another unfavorable reaction of carbonate exchange, which consequently formed the irregular carbonate linkages at not only the 3'-5' but also the 3'-3' and 5'-5' positions. Employing the well-designed monomer suppressed the carbonate exchange reaction to produce poly(thymidine) with the almost regular 3'-5'carbonate linkages.
通过在 2'-脱氧核糖核苷单体的 3'和 5'位的硅醚和羰基咪唑之间进行缩聚反应，合成了由碳酸酯键连接的聚（2'-脱氧腺苷）和聚（胸腺嘧啶）。N-苯甲酰-2'-脱氧腺苷单体与环状低聚物一起提供相应的聚碳酸酯。然而，N-苯甲酰基的脱保护导致聚合物主链的断裂。因此，研究了 N-未保护的 2'-脱氧腺苷单体的缩聚反应。然而，腺嘌呤氨基与羰基咪唑之间存在不期望的反应，形成氨基甲酸酯键。为了排除这种不利反应，采用了动态保护。强氢键取代了通常的共价键，用于降低腺嘌呤氨基的亲核性。在此，添加了与腺嘌呤氨基形成互补氢键的 3'，5'-O-二酰基胸腺嘧啶，以加入 N-未保护的 2'-脱氧腺苷单体的聚合体系中。因此，尽管产生了低聚物（M(n) = 1000-1500），但氨基甲酸酯基团的含量大大降低。动态保护试剂很容易作为甲醇可溶部分从聚合混合物中定量回收。在胸腺嘧啶单体的缩聚反应中，可能涉及另一种不利的碳酸酯交换反应，其结果是不仅在 3'-5'位，而且在 3'-3'和 5'-5'位形成不规则的碳酸酯键。采用精心设计的单体抑制了碳酸酯交换反应，从而产生了具有几乎规则的 3'-5'碳酸酯键的聚（胸腺嘧啶）。
