Synthesis of an electrophilic keto-tetraene 15-oxo-Lipoxin A4 methyl ester via a MIDA boronate.

Graphical abstract Highlights • First total synthesis of keto-tetraene 15-oxo-Lipoxin A4 has been achieved. • Synthetic approach: iterative palladium-catalyzed coupling using a MIDA boronate. • Dess-Martin oxidation of 15-position hydroxyl to electrophilic keto. • Key steps: Sonogashira, Suzuki couplings; Zinc(Copper/Silver) reduction of trien-yne. Abstract 15-oxo-Lipoxin A 4 (15-oxo-LXA 4) has been identified as a natural metabolite of the fatty acid signaling mediator Lipoxin A 4. Herein, we report a total synthesis of the methyl ester of 15-oxo-LXA 4 to be used in investigations of potential electrophilic bioactivity of this metabolite. The methyl ester of 15-oxo-LXA 4 was synthesized in a convergent 15 step (9 steps longest linear) sequence starting from 1-octyn-3-ol and 2-deoxy- d -ribose with Sonogashira and Suzuki cross-couplings of a MIDA boronate as key steps. [ABSTRACT FROM AUTHOR]