synthesis of biologically active compounds for the conrol of signal transduction by using phosphorus functional group

利用磷官能团合成了控制信号转导的生物活性化合物。1(E)-烯基膦酸盐的不对称二羟基化反应产生相应的三- α， β -二羟基膦酸盐。1(E)-烯基膦酸盐与共轭芳香取代基的AD反应具有良好的对映选择性。在1-酰基-2(E)-烯基膦酸盐外消旋混合物与ad -或-试剂的不对称二羟基化反应中，二羟基化反应的动力学速率高度依赖于1-酰基官能团的构型以及3位取代基的性质。2-苄基- 1,3 -丙二醇通过脂肪酶催化的去对称反应，在对位上具有二乙基膦单乙基或二乙基膦二氟甲基官能团，制备了（膦单乙基）苯丙氨酸和（膦二氟甲基）苯丙氨酸及其β -氨基酸同属物，即磷酸酪氨酸的稳定类似物。通过对苯基2,3-二脱氧-3-二乙基磷酸膦-5- o -（2-吡啶基）- 1 -巯基糖苷进行分子内n -糖基化，然后进行酸水解，以立体控制的方式制备了胸腺嘧啶3'-磷酸和2'-脱氧尿苷3'-磷酸亚甲基膦酸盐类似物。3-（二氧基磷硫酰基）甲基-5- o -苯甲酰- o -乙基-2,3 -二脱氧核糖与硅基胸腺嘧啶的n -糖基化反应在tic_4的存在下进行了高度非对映选择性，得到了相应的β -核苷酸类似物，产率很高。在β - n -糖基化过程中，观察到邻基参与了亚膦硫酸甲酯的功能。

Biologically active compounds for the conrol of signal transduction were synthesized by an application of phosphorus functional group.1. Asymmetric dihydroxylation of 1(E)-alkenylphosphonates afforded the corresponding threo-alpha, beta-dihydroxyphosphonates. Good enantioselectivty was obadserved in the AD reaction of 1(E)-alkenylphosphonates with conjugated aromatic substituents. In the asymmetric dihydroxylation of racemic mixture of 1-acyloxy-2(E)-alkenylphosphonates with AD-mix-alpha- or beta-reagents, the kinetic rate of dihydroxylation was highly dependent upon the configuration of the 1-acyloxy functional group as well as the nature of the substitutent at the 3-position.2. (Phosphonomethyl)phenylalanine and (phosphonodifluoromethyl)phenylalanine and their beta-amino acid congeneres, stable analogues of phosphotyrosine, were prepared from 2-benzyl-1, 3-propanediols possessing either a dithylphosphonomethyl- or diethylphosphonodifluoromethyl functionality at the para position via the lipase-catalyzed desymmetrization.3. Methylene phosphonate analogues of thymidine 3'-phosphate and 2'-deoxyuridine 3'-phosphate were prepared in a stereocontrolled manner through intramolecular N-glycosilation of phenyl 2,3-dideoxy-3-diethylphosphonomethyl-5-O-(2-pyrimydinyl)- 1 -thioglycosides, followed by acid hydrolysis. N-glycolylation of 3-(diethoxyphosorothioyl)methyl-5-O-benzoyl-O-ethyl-2,3 -dideoxy-riboses with silylated thymidine in the presence of TiCI_4 proceeded highly diastereoselectivly to give the corresponding beta-nucleotide analogues in good yield. A remarkable neighboring group participation of the methylenephosphonothioate functionality was obaserved in the course of the beta-N-glycosylation.