Synthesis and properties of 4-phosphorylated derivatives of 5-hydroxyalkylamino-1,3-oxazoles

Synthesis of novel phosphorylated peptidomimetics which contain ω-haloalkyl and ω-thiocyanoethyl residues

“…In 1 A particular attention should be paid to 13 C NMR spectral data of these compounds. Interestingly, the diethyl (2-phenyl-1,3-oxazole-4-yl)phosphonates 1e, f 19 containing in position 5 the residues of cyclic aminoalkanols -piperidin-3-ol and piperidin-4-ol, under the same conditions do not produce chlorinecontaining peptidomimetics 5a, b (Scheme 2). Such difference in the reactivity of the products 1a-d and 1e, f can be explained by the probable mechanism of this reaction.…”

“…Diethyl (5-(3-hydroxypropyl)amino)-2-phenyl-1,3-oxazol-4-yl)-phosphonate (1a) has been obtained as described previously. 19…”

“…Particular attention is drawn to the derivatives of 5-amino-1,3-oxazol-4-ylphosphonic acids, which under conditions of acidic cleavage form peptidomimetics containing the residues of phosphorylated glycine. [13][14][15][16][17][18][19] High biological activity of phosphorus-containing peptides is known. For example, selective inhibitors of cellular cymase, 20 glutathione transferase, 21,22 HCV NS3/NS4A serine protease, 23 vasoactive compounds, [24][25][26] etc., were found among these compounds.…”

“…Therefore, the study of approaches to the synthesis of phosphorylated peptidomimetics is of undoubted interest. It was previously shown that the 5-amino-1,3-oxazole derivatives containing the diethoxyphosphoryl group in position 4 are cleaved by water in the presence of various acidic agents such as acetic acid, 17,19 trifluoroacetic acid, 18,19 hydrochloric acid 34,35 and p-toluenesulfonic acid. 16 Also recently, we found that when diethyl ester (5-(2-hydroxyethyl)-N-methylamino)-2-phenyl-1,3-oxazol-4-ylphosphonic acid reacts with hydrogen chloride under anhydrous conditions, a phosphopeptidomimetic containing 2-chloroethyl fragment 18 is formed.…”

“…For this, diethyl esters of 2-aryl-1,3-oxazole-4-ylphosphonic acids 1a-f, containing in position 5 the residues 2-(methylamino)ethan-1-ol, 2-aminopropan-1-ol, piperidin-3-ol and piperidin-4-ol were synthesized according to the known procedure. 19…”