Enantioselective Synthesis of (−)-Codeine and (−)-Morphine
- 15 November 2002
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 124 (49) , 14542-14543
- https://doi.org/10.1021/ja0283394
Abstract
A new synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges employing a Pd-catalyzed asymmetric allylic alkylation to set the stereochemistry. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate, the latter available from glutaraldehyde and the Emmons−Wadsworth−Horner phosphate reagent. This intermediate requires only two steps to convert to (−)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine is formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.Keywords
This publication has 16 references indexed in Scilit:
- Enantioselective Total Synthesis of (−)-GalanthamineJournal of the American Chemical Society, 2000
- Asymmetric Total Synthesis of (+)-Codeine via Intramolecular Carbenoid InsertionThe Journal of Organic Chemistry, 1999
- Asymmetric synthesis of either enantiomer of opium alkaloids and morphinans. Total synthesis of (-)- and (+)-dihydrocodeinone and (-)- and (+)-morphineJournal of the American Chemical Society, 1993
- Convergent synthesis of (.+-.)-dihydroisocodeine in 11 steps by the tandem radical cyclization strategy. A formal total synthesis of (.+-.)-morphineJournal of the American Chemical Society, 1992
- Studies culminating in the total synthesis of (dl)-morphineThe Journal of Organic Chemistry, 1988
- Evidence for single electron transfer in the reations of alkali metal amides and alkoxides with alkyl halides and polynuclear hydrocarbonsThe Journal of Organic Chemistry, 1981
- A rapid, high-yield conversion of codeine to morphineJournal of Medicinal Chemistry, 1977
- A synthetic method for formyl→ethynyl conversion (RCHO→RCCH or RCCR′)Tetrahedron Letters, 1972
- A crystallographic examination of the structure of morphineJournal of the Chemical Society, 1955
- THE SYNTHESIS OF MORPHINEJournal of the American Chemical Society, 1952