Allylic Amines as Key Building Blocks in the Synthesis of (E)-Alkene Peptide Isosteres

作者：Skoda Erin M; Davis Gary C; Wipf Peter^*

来源：Organic Process Research & Development, 2012, 16(1): 26-34.

DOI：10.1021/op2002613

Nucleophilic imine additions with vinyl organometallics have developed into efficient, high-yielding, and robust methodologies to generate structurally diverse allylic amines. We have used the hydrozirconation/transmetalation/imine addition protocol in the synthesis of allylic amine intermediates for peptide bond isosteres, phosphatase inhibitors, and mitochondria-targeted peptide mimetics. The gramicidin S-derived XJB-5-131 and JP4-039 and their analogues have been prepared on up to 160-g scale for preclinical studies. These (E)-alkene peptide isosteres adopt type II' beta-turn secondary structures and display impressive biological properties including selective reactions with reactive oxygen species (ROS) and prevention of apoptosis.

• 出版日期2012-1