α-ヒドロキシ-β-アミノ酸を基盤とした有機化学・創薬化学研究

概要

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α-Hydroxy-β-amino acids are well known as inhibitory machinery for the development of protease inhibitors. In our ongoing efforts to develop effective aspartic protease inhibitors such as HIV-1 protease, malaria plasmepsin and human β-secretase inhibitors, the α-hydroxy-β-amino acids are also the critical core structures. In addition, the unique structure of these amino acids, in which three different functional groups, i.e. amino, hydroxyl and carboxyl groups, are located on the two adjacent asymmetric carbon atoms, also has interesting features to create new functional molecules useful in both organic chemistry and medicinal chemistry. In this article, organic and medicinal chemical applications based on the chemistry of α-hydroxy-β-amino acids will be presented, including 1) byproduction of homobislactone during the carboxyl group activation of <I>N</I>-protected-α-hydroxy-β-amino acids, 2) development of α-hydroxy-β-amino acid derived new solid-supported Evans chiral auxiliary for asymmetric synthesis, 3) development of a novel and efficient method for the synthesis of difficult sequence-containing peptides, and 4) O-N intramolecular acyl migration of α-hydroxy-β-amino acids for the development of water-soluble prodrugs of taxoids (isotaxoids).
社団法人有機合成化学協会の論文
2005-06-01