14C-labeling of a novel prostacyclin I1 derivative, SM-10902

Abstract

(+)-Methyl [2-[(2R,3aS,4R,5R,6aS)-octahydro-5-hydroxy-4-[(E)-(3S,5S)-3-hydroxy-5-methyl-1-[3-14C]nonenyl]-2-pentalenyl]ethoxy]-acetate ([nonenyl-3-14C]SM-10902) (1) was labeled with carbon-14 for use in mammalian metabolic studies. The synthesis was achieved in 7 steps from [14C]carbon dioxide: including: 1) Grignard reaction, 2) esterification, 3) condensation with dimethyl methylphosphonate, 4) Wittig-Horner reaction, 5) separation of isomers by HPLC. Stereoselective reduction of the protected ketone with sodium borohydride in the presence of cerium (III) chloride and subsequent desilylation produced 1. The overall yield was 11.1% from Ba[14C]CO3. © 1997 John Wiley & Sons, Ltd.