合成路线1

A new synthesis of rimexolone from prednisolone has been described: The reaction of prednisolone (I) with tosyl chloride in pyridine gave the 21-tosylate (II), which was treated with sodium iodide in acetone to yield the 21-iodo derivative (III). The deiodination of (III) with refluxing acetic acid afforded 21-deoxyprednisolone (IV), which was dehydrated with semicarbazide in water at 80-5 C yielding the trienone (V). The silylation of (V) with TMS-Cl and pyridine gave the protected compound (VI), which was methylated with methyl iodide and lithium bis(trimethylsilyl)amide to the 21-methyl derivative (VII). A new methylation of (VII) with Me2Cu(CN)Li2 followed by silylation with TMS-Cl afforded the silylated dimethyl enol ether (VIII), which was submitted to a third methylation with methyl iodide and benzyltrimethylammonium fluoride in THF giving the silylated 16,17,21-trimethyl derivative (IX). Finally, this compound is desilylated to rimexolone with 6M HCl in methanol.