Total Synthesis\nof Marformycins A and D

We report the synthesis of the antimicrobial cyclodepsipeptides\nmarformycin A (<b>1</b>) and marformycin D (<b>2</b>)\nusing a solid-phase approach. A scalable solution-phase synthesis\nof the γ-hydroxypiperazic acid subunit in <b>2</b>, starting\nfrom <i>cis</i>-hydroxyproline, is also described. Structural\nanalysis of <b>1</b> and its Leu-<i>epi</i> congener\ndemonstrates conformational differences that may underlie their divergent\nantimicrobial activities. The described approach enables further development\nof conformation–activity relationships within this class of\ndepsipeptide natural products.