Design and Synthesis of Cyclofructans as Novel Inclusion Molecules for Clinical Use

瞄准创造新颖的含分子用于临床用途，我们研究了环氟虫的设计和化学合成，因为那些有效的建筑块已经进化和利用于果糖-β（2→1）-分子作为良好的循环模拟，D-果糖被转化为区域性受保护的中间体， 3，4，5-三-O-苯并基-1，2-O-异丙酰亚胺-β-D-果糖（1），在转向的情况下，将氟代糖作为1-O-乙酰-3，4，5-三-O-苯并-β-D-氟代糖基氟（2），并作为氟代糖基接受者，例如，3，4，5-tri-O-benzyl-β-D-fructopyranose（3）和3，4，5-tri-O-benzyl-2-methoxy methyl-β-D-fructopyranose （4）在良好的产量下，在刘易斯酸存在的受体3中的水果化（SnCl2·D22·D2） resulted in an efficient entry to a minimum size of cyclofructan，CF-2 in quantitative yield。On the other hand， a similar fructosylation （Cp-D22-ZrCl-D22-D2 / CH-D22-D2） of 4 with 2 afforded a disaccharide building block，I.e.，O-β-D-fructopyranosyl-（2→1）- β-D-fructopyranose衍生物（5）在57%的yield。“不愉快的5”被转换成不愉快的捐赠者（2'-F deriv.）6）和接受者（1-OH和2'-OMOM衍生物）（七）。我们评估了两种组合时尚的类型，I.E.，在捐赠者2和接受者7之间，或捐赠者6和接受者4之间，两者都给予了在加利福尼亚州想要的水果糖基三氯（8）。20%的收益率（Cpy-D22-ZrCly-D22-ZrCly-D2-D2-Cly-D22-D2）。最后，对非吸入器捐赠者（6）和接受器（7）已实现线性β（2→1）-链接的fructopyranosyl四重奏（8），应被注射到循环生成cyclofructan，CF-4。在调查中发现的CF-2和氟代寡核苷酸的功能性分析。

Aiming at creation of novel inclusion molecules for clinical use, we investigated design and chemical synthesis of cyclofructans, for which efficient building blocks have been evolved and utilized for fructosyl-β(2→1)-oligomers as well as their cyclic analogues.D-Fructose was converted into a regioselectively protected intermediate, 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-fructopyranose (1), which in turn was led to a fructosyl donor such as 1-O-acetyl-3,4,5-tri-O-benzyl-β-D-fructopyranosyl fluoride (2) and to fructosyl acceptors, e.g., 3,4,5-tri-O-benzyl-β-D-fructopyranose (3) and 3,4,5-tri-O-benzyl-2-methoxy methyl-β-D- fructopyranose (4) in good yield.Fructosylation of the acceptor 3 with the donor 2 in the presence of Lewis acids (SnCl2ィイD22ィエD2 or CP2ィイD22ィエD2 HfClィイD22ィエD2 /CHィイD22ィエD2ClィイD22ィエD2) resulted in an efficient entry to a minimum size of cyclofructan, CF-2 in quantitative yield. On the other hand, a similar fructosylation (CpィイD22ィエD2 ZrClィイD22ィエD2 / CHィイD22ィエD2 ClィイD22ィエD2) of 4 with 2 afforded a disaccharide building block, I.e., O-β-D-fructopyranosyl-(2→1)- β-D-fructopyranose derivative (5) in 57% yield. The disaccharide 5 was converted into a disaccharide donor (2'-F deriv., 6) and an acceptor (1-OH and 2'-OMOM deriv., 7). We evaluated two types of coupling fashion, I.e., between donor 2 and acceptor 7, or donor 6 and acceptor 4, both of which gave the desired fructosyl trisaccharide (8) in ca. 20% yield (CpィイD22ィエD2 ZrClィイD22ィエD2/CHィイD22ィエD2 ClィイD22ィエD2).Finally, coupling of the disaccharide donor (6) and the acceptor (7) was achieved to give linear β(2→1)-linked fructopyranosyl tetramer (8), which should be subjected to cyclization to generate a cyclofructan, CF-4. Functional analyses of CF-2 and fructosyl oligosaccharides obtained are under investigation.