Expeditious synthesis of the key unnatural aminoacid in the formal asymmetric total synthesis of (-)-Jorumycin and bioactive tetrahydroisoquinoline alkaloids

Abstract

The synthesis of the enantiopure aminoacid, key intermediate in the total synthesis of (-)-Jorumycin and of various bioactive tetraidroisoquinoline alkaloids analogues, a class of compounds with antitumor and antibiotic activities, has been accomplished starting from 2,4-dimethoxy-3-methyl-benzaldehyde 1 in only 5 steps and in a very high yield. This synthesis, based on a Negishi reaction between a 5-iodo-2,4-dimethoxy-3-methylphenol and N-(tert-Butoxycarbonyl)-3-iodo-L-alanine methyl ester, permits an easy access to the intermediate, and the formal asymmetric total synthesis of (-)-Jorumycin and tetrahydroisoquinoline alkaloids of the same family, in a very shorter way with respect to the syntheses previously reported