Source 1

Chi, H.; Stratton, T.; Baran, H. Concise Total Synthesis of Herqulines B and C. Journal of the American Chemical Society 2018, 141.1, 29-32.

The focus of this study involves the total synthesis of the herquline molecule series, which historically could only be isolated from natural items. Herquline B and C have practical medical use, as a platelet inhibitor. Total synthesis implies beginning with “readily commercially available” starting reagents. It’s synthesis has been attempted several times before. Beginning with a known tyrosine building block, amide bond formation mediated by HaTU and DIPEa in DMF yields a dipeptide. This is then subjected to diketopiperazine ring forming conditions by reaction with HC2OH under heat. The product then undergoes Pd-catalyzed macrocyclization. This then undergoes 4 separate reduction reactions then yield the Herquline C product, the first of which being a Birch reaction to deliver an enol ether. The next two reductions were accomplished by the chemoselective excision of the oxygens resulting from DKP, done using DIBaL. The final reduction to access the Herquline products was another Birch reduction, done after exposure to ethylene glycol in the presence of PTSa.