Syntheses of structurally diverse amino acids, including δ-hydroxylysine, using the acyl nitroso Diels–Alder reaction

By virtue of its ability to introduce amino and hydroxy functionalities in a 1,4-relationship with fully controlled relative stereochemistry, the acyl nitroso Diels–Alder (ANDA) reaction is ideally suited to the synthesis of structurally diverse, including hydroxylated, amino acids. The major issue to be tackled is that of regiochemistry in the ANDA addition to unsymmetrical dienes. The transformation of three diverse types of ANDA adducts into amino acids is described, in particular, the synthesis of δ-hydroxylysine, an important constituent of collagen, as a single (2SR, 5SR) diastereoisomer in protected form.

Graphical abstractThe acyl nitroso Diels–Alder reaction is ideally suited to the synthesis of diverse amino acids, as it introduces N and O functionalities in a 1,4-relationship with full control of relative stereochemistry. We have utilised this reaction in a short synthesis of (±)-δ-hydroxylysine, an important constituent of collagen, and describe two further syntheses together with corroborative X-ray structural data.Figure optionsDownload full-size imageDownload as PowerPoint slide