DESIGN AND SYNTHESIS OF NEW POLYESTER DENDRIMERS, AND APPLICATION TO DRUG DELIVERY SYSTEM

1. 我们的新Michael加成反应在5M KOH水溶液中的范围和限制。我们发现这个简单的米歇尔反应只适用于1,3-酮酯或1.3-二酯与在碱性溶液中携带大量或稳定烷基的丙烯酸酯的反应。“丙二酸枝状大分子”的合成。通过将丙二酸苄酯加成到丙烯酸丁酯上，再将乙二醇加成到甲醛羧基上，制备了该结构块。通过HCOOH重复[去保护]，再通过EDCI/DMAP缩合]反应，合成了[G3-32tBu]的“丙二酸枝状大分子”。“丙二酸枝状大分子”的表征。这些树状大分子的分子量通过ESI-MS测量得到了证实。利用COSY、HMBC和HMQC等多种测量方法，对核磁共振光谱中的Hi和C^<13>化学位移进行了赋值。通过对CDCl_3中G3树状大分子的NOESY测量分析，提出了G3树状大分子的后折叠形态，外围的tBu位于空隙深处。采用动态光散射法测定了G0~G3在MeOH中的粒径。这些树状大分子的粒径比拉伸构象的计算结果小40%左右。这些树状大分子在给药系统中的应用。成功地合成了一个外围有16个甘露糖分子（用于靶向和提高在水中的溶解度），焦点有蒽的聚酯树突。利用小鼠腹膜细胞进行的生物测定证实了这种树突的有效摄取。

1. The scope and limitation of our new Michael addition reaction in a 5M aqueous KOH solution. We found that this simple Michel reaction was useful only for the reaction of 1,3-ketoesters or 1.3-diesters with acrvlates both carrying bulky or stable alkyl groups in a basic solution.2. Synthesis of "malonate dendrimer". The building block was prepared from the Michael addition of benzyl malonate to t-butyl acrylate, followed by the addition of ethylene glycol to the forcal carboxyl. The "malonate dendrimers" were synthesized up to [G3-32tBu] by repetition of [deprotection by HCOOH, then condensation by EDCI/DMAP] reactions.3. Characterizion of the "malonate dendrimer". The molecular weights of these dendrimers were confirmed by ESI-MS measurements. The assignments of Hi and C^<13> chemical shifts of NMR spectra were carried out using various kinds of measurements such as COSY, HMBC and HMQC, etc. The back-folded shape of G3 dendrimer in CDCl_3 with the peripheral tBu located in the void space deeply inside was suggested from the analysis of NOESY measurements. The'particle size measurements in MeOH for G0~G3 were carried out using the dynamic light scattering method. The particle sizes of these dendrimers are ca. 40% smaller than those calculated for the stretched conformation.4. Application of these dendrimers to drug delivery system. A polyester dendron with 16 mannose molecules (for targeting and increase of solubility in water) at the periphries and anthracene at the focal point was successfully synthesized. The bioassay using mouse peritoneal cells confirmed the efficient uptake of this dendron.