Enantioselective Total Synthesis of (+)-Colletoic Acid via Catalytic Asymmetric Intramolecular Cyclopropanation of an α‑Diazo-β-keto Diphenylphosphine Oxide

Abstract

The enantioselective total synthesis of (+)-colletoic acid, a potent naturally occurring 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, is described. This total synthesis features a highly enantioselective catalytic asymmetric intramolecular cyclopropanation of an α-diazo-β-keto diphenylphosphine oxide and five highly stereoselective reactions (cyclopropane opening, Diels–Alder reaction, iodolactonization, alkene formation, and reduction of α,β-unsaturated carboxylic acid)