Synthesis of two fragments of the natural product Pepticinnamin E via Ugi reactions

New strategy has been developed for the total synthesis of the natural product Pepticinnamin E, a naturally occurring compound that has important applications as a possible antitumor agent, being a potential inhibitor of the enzyme farnesyltransferase1,2. In this new approach, we synthesized two key fragments via Ugi reactions. Key fragment 1: the synthesis of the trisubstituted benzaldehyde was carried out in three steps using isovaniline as starting material, and the isocyanide synthesis was performed in two steps from L-phenylalanine methyl ester hydrochloride. It was also necessary to protect the phenol of the carboxylic acid (Boc-D-tyrosine), and the amine used was the commercially available methylamine. Key fragment 2: the isocyanide was prepared in 2 steps from cyclohexanone and used in situ in the Ugi reaction, which was followed by protecting group removal with subsequent cyclization to the diketopiperazine. Efforts are under way to synthesize the last fragment and couple them together