TOTAL SYNTHESIS OF (-3-OXACARBACYCLIN - 2 - STEREOSELECTIVE DEPROTONATION AND COMPLETION OF THE SYNTHESIS())

The asymmetric synthesis of (+)-3-oxacarbacyclin (1) from cis-bicyclo[ 3.3.0]octane-2,5-dione has been achieved. A notable feature in this sy nthesis is an asymmetric Horner-Wadsworth-Emmons (HWE) reaction. A fur ther key step is the stereoselective deprotonation of a chiral bicycli c ketone, having a high local symmetry about the carbonyl group, with lithium (R,R)-bis(phenylethyl)amide in the presence of lithium chlorid e. The route described also allows the synthesis of the anti-thromboti c and anti-metastatic prostacyclin analogs cicaprost and eptaloprost. The flexibility of this route should also provide access to further si de-chain modified analogs of 1.