Tetrahydro‑4H‑(pyrrolo[3,4‑d]isoxazol-3-yl)methanamine: A Bicyclic Diamino Scaffold Stabilizing Parallel Turn Conformations

A tetrahydro-4H-(pyrrolo[3,4-d]isoxazol-3-yl)methanamine
scaffold was designed as a diamino derivative to stabilize parallel turn conformations. Its synthesis took advantage of a [1,3]-dipolar cycloaddition reaction between the nitrile oxide derived from the inexpensive enantiopure Lphenylalanine and N-benzyl-3-pyrroline. Two diastereoisomers were formed, whose distribution depends on the selected base. 3aR,6aS-Isomer is favored in organic bases, which formation is driven by π-interactions. However, the above interactions were significantly prevented using an inorganic base due to the chaotropic effect of the cation, decreasing the amount of the above isomer.
Finally, we demonstrated that this isomer is able to stabilize parallel turn conformations when inserted in short peptide sequences.

DOI: 10.1021/acs.joc.8b01299