Phosphazene High Polymers with Steroidal Side Groups

Steroidal residues derived from desoxoestrone (III), estrone (IV), 17β-estradiol (V), 17α-ethynylestradiol (VI), estradiol 3-methyl ether (VII), and 1,4-dihydroestradiol 3-methyl ether (VIII) have been linked to a polyphosphazene chain via the sodium salt of the steroidal hydroxy function. The degree of replacement of P-Cl bonds by P-OR units was in the range 0.5-40%, depending on the reaction conditions. The residual chlorine atoms were removed by reaction with methylamine, ethyl glycinate, or n-butylamine. Stable polymers of structure XIV were obtained when the steroidal units were linked to phosphorus through an aryloxy residue. However, linkage through an alkoxy residue led to instability and chain cleavage. The use of ethyl glycinato residues as cosubstituent groups yielded hydrolytically degradable polymers. Comparisons are made between these high-polymeric reactions and those of small-molecule cyclophosphazene models.