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

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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.