Unified Synthesis of Densely Functionalized Amino Acid Building Blocks for the Preparation of Caprazamycin Nucleoside Antibiotics

Naturally occurring caprazamycin nucleoside antibiotics are promising lead structures for the development of novel antimicrobial agents. However, efficient synthetic access to the structurally complex caprazamycin scaffold is not trivial. The stereocontrolled construction of the seven-membered diazepanone core moiety is particularly challenging. So far, two main strategies to build up the diazepanone system (by reductive amination or Mitsunobu reaction) have been established, but they require different non-proteinogenic amino acid building blocks to be connected with the nucleoside moiety. Previously, these amino acid structures were obtained from different starting materials with no overlap of the according synthetic routes. In this work, we describe an efficient unified synthetic access to densely functionalized amino acid building blocks for both approaches towards the diazepanone core. This will enable the preparation of caprazamycin analogues with high modularity and variability.