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

Mer-N5075A (1) and alpha -MAPI and beta -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. (C) 2001 Elsevier Science Ltd. All rights reserved.