Enantioselective Synthesis of 12-epi-PGF_2α and 12,15-diepi-PGF_2α

Abstract

An enantioselective synthesis of 12-epi-PGF2 α (3) and 12,15-diepi-PGF2 α (4), PG-like compounds that are probably generated in vivo by nonenzymatic, free-radical-induced peroxidation of arachidonic acid, has been achieved starting from the commercially available Corey lactone (9). The key strategy involves SmI2 reduction of the γ,δ-epoxy-α,β-unsaturated ester 7, followed by in situ trapping with hexanal; subsequent hydrogenation and decarboxylation affords the stereoselective construction of the lower side chain. This new method is expected to provide a convenient access to various PG-like isoprostanes derived from oxidation of arachidonic acid and cis-4,7,10,13,16,19-docosahexaenoic acid.

Beyond Prostaglandins—Chemistry and Biology of Cyclic Oxygenated Metabolites Formed by Free‐Radical Pathways from Polyunsaturated Fatty Acids

“…[235] In 1999, Cha and co-workers developed an approach to 15-F 2c -IsoP (15-2 b) starting from commercially available benzoyl-protected Corey lactone (206,Scheme 61). [236] An…”

“…[235] In 1999, Cha and co-workers developed an approach to 15-F 2c -IsoP (15-2 b) starting from commercially available benzoyl-protected Corey lactone (206, Scheme 61). [236] An E1cB elimination of the benzoyl group in 206 with DBU and a subsequent Luche reduction gave the corresponding allylic alcohol, which was subjected to Sharpless epoxidation conditions to afford epoxy alcohol 207 in 72 % yield. The g,depoxy-a,b-unsaturated ester unit 208 was introduced by a Swern oxidation and a Wittig reaction.…”

Recent advances in the stereoselective synthesis of isoprostanes and neuroprostanes

“…With pure 80a and 80b in hand, each compound was subjected separately to DIBAL reduction, followed by olefination with (4-carboxybutyl)triphenylphosphonium bromide and potassium tert-butoxide to furnish 81a and 81b, respectively, in 81-89% yield. Finally, desilylation with 3:1:1 HOAc-THF-H 2 O at room temperature yielded 1a and 1b in 85% yield (Lai et al, 1999).…”

Jenseits von Prostaglandinen – Chemie und Biologie radikalisch gebildeter cyclischer oxygenierter Metabolite von mehrfach ungesättigten Fettsäuren

“…Das käufliche Benzoyl‐geschützte Corey‐Lacton ( 206 ) kann auch zur Synthese von IsoP wie 15‐F 2c ‐IsoP (15‐ 2 b ) eingesetzt werden, wie Cha und Mitarbeiter 1999 zeigten (Schema ) 236. E1cB‐Eliminierung der Benzoyl‐Gruppe in 206 mit DBU und anschließende Luche‐Reduktion führten zum entsprechenden Allylalkohol, aus dem durch Sharpless‐Epoxidierung der Epoxyalkohol 207 in 72 % Ausbeute zugänglich war.…”