General synthesis of conformationally constrained noncanonical amino acids with C(sp3)-rich benzene bioisosteres

Recent years have seen novel modalities emerge for the treatment of human diseases resulting in an increase in beyond rule of 5 (bRo5) chemical matter. As a result, synthetic innovations aiming at enabling rapid access of complex bRo5 molecular entities become increasingly valuable for medicinal chemists’ tool-kits. Herein, we report the general synthesis of a new class of noncanonical amino acids (ncAA) with a cyclopropyl back-bone to achieve conformational constraint and bearing C(sp3)-rich benzene bioisosteres. We also demonstrate preliminary studies towards utilities of these ncAA as building blocks for medicinal chemistry research.