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

Josep Bonjoch,* Daniel Solé, Silvina García-Rubio, and Joan Bosch*
Contribution from the Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, 08028 Barcelona, Spain
J. Am. Chem. Soc., 1997, 119 (31), pp 7230–7240
DOI: 10.1021/ja970347a
Publication Date (Web): August 6, 1997
Copyright © 1997 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

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.

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue August 06, 1997
  • Received February 3, 1997

Recommend & Share

Related Content

Other ACS content by these authors: