A Concise Total Synthesis of Tryprostatins A and B and Epimers

A concise four-step total synthesis of tryprostatins A and B has been developed, starting from commercially available gramine. The key step features a coupling between a <i>C</i>2<i>,N'</i>-diprenylated gramine salt and a diketopiperazine mediated by quinine as a bifunctional base. The synthesis afforded tryprostatins A and B along with their respective epimers in 1:1 ratios as determined by isolation and separation via column chromatography. The overall combined yields were 22% for tryprostatin A and its epimer and 44% for tryprostatin B and its epimer.