A General Synthetic Entry to Strychnos Alkaloids of the Curan Type via a Common 3a-(2-Nitrophenyl)hexahydroindol-4-one Intermediate. Total Syntheses of (±)- and (−)-Tubifolidine, (±)-Akuammicine, (±)-19,20-Dihydroakuammicine, (±)-Norfluorocurarine, (±)-Echitamidine, and (±)-20-Epilochneridine1

Citations Over TimeTop 10% of 1997 papers

Abstract

A general strategy for the synthesis of pentacyclic Strychnos alkaloids with the curan skeleton has been developed. It utilizes 3a-(2-nitrophenyl)hexahydroindol-4-one (23), which was prepared from 2-allyl-2-(2-nitrophenyl)-1,3-cyclohexanedione (15), as the common, pivotal intermediate. Three different procedures have been employed for the closure of the bridged piperidine D ring from 23: (i) an intramolecular Michael-type conjugate addition; (ii) a Ni(COD)2-promoted biscyclization that assembles B and D rings in a single synthetic step, and (iii) an intramolecular cyclization of an enone−propargylic silane system. When necessary, depending on the procedure used, introduction of the oxidized one-carbon substituent at C-16, closure of the indole ring, and/or adjustment of the functionality of the C-20 two-carbon chain constitute the last stages of the synthetic route to the title alkaloids. The procedure involving the cyclization of a propargylic silane has been successfully extended to the enantiospecific synthesis of (−)-tubifolidine starting from the enantiopure 3a-(2-nitrophenyl)hexahydroindolone (−)-51, which was prepared taking advantage of the prochiral character of cyclohexanedione 15.

Related Papers

• → Synthesis of Enantiopure γ‐Lactones via a RuPHOX‐Ru Catalyzed Asymmetric Hydrogenation of γ‐Keto Acids(2018)26 cited
• → Synthesis of Enantiopure 5-Substituted 2,3-Methanopyrrolidines by Cyclization of Enantiopure α-Branched α-N-Homoallylamino Nitriles(2012)8 cited
• → A Valuable Synthetic Route to the Enantiopure Functionalized N‐Substituted Aziridines(2004)1 cited
• → ChemInform Abstract: Efficacious and Rapid Metal‐ and Solvent‐Free Synthesis of Enantiopure Oxazolines.(2015)
• → ChemInform Abstract: Chiral Pyridin‐3‐ones and Pyridines: Syntheses of Enantiopure 2,4‐Disubstituted 6‐Hydroxy‐1,6‐dihydro‐2H‐pyridin‐3‐ones, 2,3‐Disubstituted 4‐Iodopyridines, and Enantiopure 2,3‐Disubstituted 4‐Pyridinemethanols.(2012)