Total synthesis of (+)-10,10-difluorothromboxane A2 and its 9,11 and 15 stereoisomers

An efficient total synthesis of the biologically highly active, stable (+)- 10, 10-difluorothromboxane A 2 , possessing the absolute configuration of TXA 2 , from the chiral synthon (-)-5 is described. The key intermediate, the aldehyde 25, is prepared in 16 steps with a total yield of 8.8%, which compares with 1.95% in 14 steps by our previously reported chemical-enzymatic route. Diastereoselectivity is high in all but one of the steps, the Reformatsky reaction, which leads to 13 and 14. However, both epimers have been converted efficiently to 25