The Diels-Alder approach for the synthesis of tetralin-based alpha-amino acid derivatives and their modification by the Suzuki-Miyaura cross-coupling reaction

Abstract

Tetralin-based alpha-amino acid (AAA) is a constrained analogue of phenylalanine (Phe) and is used extensively in the design and synthesis of a variety of bioactive peptides. Due to the nonavailability of simple synthetic methods to deliver complex cyclic AAAs, only simplest members of this class have been used in the peptide area. In this regard, we have developed a new method to prepare various highly functionalized tetralin-based unusual AAA derivatives 22, 37-43 by trapping o-xylylene (or o-quinodimethane) intermediate with methyl 2-acetamidoacrylate (12). In addition, we have also modified the diidotetralin derivative 40 by the Suzuki-Miyaura cross-coupling reaction.