Synthesis of 10-Oxa-11-deoxyprostaglandin E1

Synthesis of 10-oxa-11-deoxyprostaglandin E1 (2b) and related compounds (2a, 17b, and 20) was successfully accomplished starting from nonanedioic acid (3). Decarboxylation of 3, 3-di-tert-butoxycarbonyl-2-(6-methoxycarbonyl) hexyl-4-butanolide (6) by heating gave predominantly trans-3-carboxy-2-(6-methoxycarbonyl) hexyl-4-butanolide (7a). Conversion of 7a into the hydroxymethyl lactone (13) and the Pfitzner-Moffatt oxidation of 13 provided trans-3-formyl-2-(6-methoxycarbonyl) hexyl-4-butanolide (14) which served as a key intermediate. The Wittig reaction of 14 with dimethyl 2-oxoheptylphosphonate gave enone (15) which was converted to 10-oxa-11-deoxy PGE1 methyl ester (16b) by NaBH4 reduction. Alkaline hydrolysis of 16b and relactonization of the resulting diacid (17b) gave 2b as crystals in a good yield.