First total synthesis of Mer-N5075A and a diastereomeric mixture of α and β-MAPI, new HIV-I protease inhibitors from a species of Streptomyces

Abstract Mer-N5075A ( 1 ) and α-MAPI and β-MAPI ( 2 and 3 ) produced from a species of Streptomyces are new anomalous tetrapeptides having potential HIV-I protease inhibitory activity. The first total synthesis of 1 and a diastereomeric mixture of 2 and 3 was achieved simply by a route connecting two dipeptides. The synthetic method is applicable for synthesis of Mer-N5075A analogues, such as GE20372 A and B ( 4 and 5 ) and other chemically modified compounds. In addition, the inhibition of HIV-1 Protease and anti HIV activity by the compounds 1 , a mixture of 2 and 3 , and 24 , 25 , and 26 were described.