Thromboxane B₂ (pictured) is a metabolite of thromboxane A₂, a signaling compound that is involved in the formation of blood clots. Thromboxane B₂ is useful as a marker and synthetic precursor for thromboxane A₂. It also is an interesting target for total synthesis. However, existing approaches to its preparation are lengthy.

Changcheng Jing and Varinder K. Aggarwal, University of Bristol, UK, have developed a concise, twelve-step, asymmetric synthesis of thromboxane B₂. The team started from succinaldehyde, which was converted to an enal-lactone using an organocatalytic aldol reaction. The enal-lactone was converted to a para-methoxybenzyl acetal and then subjected to a conjugate addition of an alkenyl side chain, a selective ozonolysis, and a Baeyer–Villiger oxidation to give a key lactone intermediate. A highly selective Wittig olefination was used to install the Z-alkene, followed by deprotection and hydrolysis steps to give the final product.

The researchers obtained thromboxane B₂ in twelve steps with an overall yield of 5 %. The enal-lactone intermediate that the team obtained from succinaldehyde can also be used to synthesize other compounds that are structurally related to thromboxane B₂.

• Total Synthesis of Thromboxane B₂ via a Key Bicyclic Enal Intermediate,
  Changcheng Jing, Varinder K. Aggarwal,
  Org. Lett. 2020.
  https://doi.org/10.1021/acs.orglett.0c02299