Although the final retrosynthetic blueprint employed to arrive at 1 is depicted in Figure , it is the culmination of multiple failed routes that preceeded it. Strategies wedded to macrolactamization, Suzuki, and Heck tactics were all extensively investigated. A Ultimately an approach featuring Larock-based macrocylizations successfully accessed the natural product using inexpensive amino acids and arenes as building blocks (Figure ). To begin, two of the key unnatural amino acids required for the synthesis were fashioned using decarboxylative cross coupling methodology (Scheme 1A). Previously, such derivatives were prepared from serine in two steps and required the use of copper cyanide or from 2-prop-2-ynoxyoxane in four steps 21,25 using Schöllkopf's chiral auxiliary. By employing a decarboxylative alkynylation approach , a scalable synthesis of 9 was achieved in one step from commercially available 6. Alkyne-dipeptides 12 and 14 could be divergently accessed from 6, either through SeO2-based oxidation (via 10/11) followed by peptide coupling or through peptide coupling (via 13) and deprotection, respectively. Although diastereomer 11 ultimately proved to be the desired isomer, both 10 and 11 were needed in this study (vide infra).