Synthesis of nitrogen- and oxygen-containing macrocycles - Derivatives of lithocholic acid

Palladium-catalyzed amination of 3,24-bis(3-bromophenoxy)cholane (4) with various polyamines and polyoxadiamines 5 taken in 1:1 ratio was used for the synthesis of the macrocycles 6, which contain steroidal and polyamine moieties and were obtained in 38-65 % yields. The same reaction with excess polyamine (2.2-3 equiv) provided bis(polyamino) derivatives of 3,24-diphenoxycholane 7 in excellent yields, whereas the diarylation of polyamines with two equivalents of 3,24-bis(3-bromophenoxy)cholane afforded their bis(steroidal) derivatives 8. Compounds 7 and 8 were employed in the syntheses of cyclodimers 9, which possess two steroidal and two polyamine fragments; the efficiency of two methods was compared.