The retrosynthetic strategy illustrated in Scheme 1A presented four main tactical challenges that needed to be overcome. First, a pivotal C-H amination to unlock the fivemembered guanidine subunit required invention (14). Next, the precise installation timing and identity of the guanidine units needed to be determined (15). To enable maximal convergency, a method to couple the pyrrolidine and diamine fragments was required (16). Finally, a simple path to enantiopure trans-3-hydroxy proline was needed. With regards to the prohibitively expensive proline fragment 17 (ca. $100/gram), numerous approaches were evaluated as outlined in the SI. Ultimately it was found that a selective biocatalytic C-H hydroxylation of L-proline could be achieved using a novel fungal oxygenase.