Synthesis of biologically compounds to control of the signal transduction by an application of phophorus functional group

合成了多种控制信号转导的生物活性化合物。结果可分为以下几类。采用含二氟甲基膦酸片段的环烷基和无环烷基间隔物缩合法合成了多种具有A的核苷酸类似物，并与核酸碱基缩合，获得了对嘌呤核苷磷酸化酶的高抑制活性。以l -丝氨酸和d -丝氨酸为起始原料，合成了含有二氟亚甲基膦酸片段的鞘磷脂类似化合物，以评价其对鞘磷脂酶的抑制能力。通过还原相应的酮，合成了具有二氟亚甲基膦酸盐基团的环丙基甲醇。4 .以含二氧膦基二氟甲基的1,3 -丁二烯为原料，用Diels-Alder反应合成了含二氧膦基二氟甲基的环己烷衍生物。以3-取代1,3 -丙烷二醇为关键反应，应用动力学拆分技术制备了具有核酸碱基的β-氨基酸衍生物。在手性催化剂作用下，a-氨基酸加氢磷酸化合成手性β-氨基-α-羟基-h -膦酸盐。

A variety of biologically active compounds to control of the signal transduction were synthesized. The results can be classified into following items1.A variety of nucleotide analogues having a were cynthesized by condensation of cyclic and acyclic alkyl spacer containing difluoromethylenephosphonic acid moiety were synthesized and condensed with nucleic acid base to get high inhibitory activity to purine nucleoside phosphorylase.2.Sphingomyelin analogous compounds containing difluoromethylenephosphonic acid moiety were synthesized starting with L-serine and D-serine for the evaluation of their inhibitory potency to sphingomyelinase.3.Cyclopropyl carbinols possessing a difluoromethylenephosphonate group were synthesized by reduction of the corresponding ketones.4.Cyclohexane derivative possessing a (diethoxyphosphinyl)difluoromethyl unit were synthesized by the Diels-Alder rection of the 1, 3-butadinene possessing a (diethoxyphosphinyl)difluoromethyl group with dienophiles.5.β-Amino acid derivatives possessing a nucleic acid base were prepared by an application of kinetic resolution of 3-subsituted 1, 3-propane diol as the key reaction.6.Diastereoselective synthesis of chiral β-amino-α-hydroxy-H-phosphinates by hydrophosphinylation of a-amino acids in the prsence of chiral catalyst.