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The direct and highly diastereoselective synthesis of 3,4-epoxy-2-piperidones. Application to the total synthesis and absolute configurational assignment of 3α,4α-epoxy-5β-pipermethystine.
- Source :
-
Organic & biomolecular chemistry [Org Biomol Chem] 2017 Dec 19; Vol. 16 (1), pp. 77-88. - Publication Year :
- 2017
-
Abstract
- The substrate-controlled asymmetric total synthesis and absolute configurational assignment of biologically active 3α,4α-epoxy-5β-pipermethystine, a minor component in the aerial parts of kava, has been achieved by featuring, as a key step, the environmentally friendly and direct synthesis of 2,3-epoxyamides from allyl amines. By using the chiron approach, first a carbohydrate-derived dehydropiperidine was prepared and subjected to a stereoselective tandem C-H/C[double bond, length as m-dash]C oxidation reaction. In this attempt, the required α,α-trans-epoxy-2-piperidone skeleton of the kava metabolite precursor was not achieved, although the tandem oxidation was highly stereoselective. However, starting from non-carbohydrate 3-hydroxy-4,5-dehydropiperidine, and using the same tandem oxidation, the target intermediate was obtained in high yield and complete unprecedented anti-stereoselectivity. Since the proposed mechanistic course of this tandem oxidation implies the transient formation of an α,β-unsaturated amide followed by the subsequent epoxidation reaction, this second approach supports the previously established biotransformation proposal of (-)-pipermethystine to (-)-3α,4α-epoxy-5β-pipermethystine.
Details
- Language :
- English
- ISSN :
- 1477-0539
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Organic & biomolecular chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 29192703
- Full Text :
- https://doi.org/10.1039/c7ob02700a