Total Synthesis of Sacrolide A and Cytotoxic Evaluation

Sacrolide A, a 14‐membered macrolactone oxylipin, was first isolated from the edible freshwater cyanobacterium Aphanothece sacrum and identified as a potent antimicrobial and cytotoxic metabolite. Given the rising use of A. sacrum as a luxury food ingredient and concerns over potential toxicity from excessive consumption, we achieved the total synthesis of (+)‐sacrolide A to enable further biological evaluation. Our highly convergent strategy involved the coupling of an α‐hydroxylated aldehyde with a propargylic alkyne and macrolactonization as key steps, along with Wittig coupling and Noyori reduction, leading to an efficient 15‐step longer linear sequence. This approach facilitated an in‐depth assessment of sacrolide A's cytotoxicity on liver and colon cells, shedding light on its potential health implications and bioactive properties.