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. A convenient method for the synthesis of nitrogen‐ and oxygen‐containing macrocycles (an example of which is shown here) incorporating steroidal moieties has been elaborated. The method is based on intramolecular catalytic diamination of 3,24‐bis(3‐bromophenoxy)cholane.