Total Synthesis of Hemiketal D2 via a Convergent Coupling Strategy.

Hemiketal D2 (HKD2) is a recently identified eicosanoid produced from arachidonic acid via a crossover pathway involving 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2), and has been shown to stimulate angiogenesis by inducing endothelial cell tubulogenesis. However, its limited availability by enzymatic reactions has hindered detailed biological investigation. Herein, we report the first total synthesis of HKD2 through a convergent coupling of three segments bearing all required stereogenic centers. Key transformations include addition of dithiane anion to a lactone segment to construct the hemiacetal moiety and a late-stage cross metathesis with carboxylic acid segment to complete the synthesis.