biosynthesis of ephedrine

[thissuks]

The biosynthesis of ephedrine
Grue-Sorensen, Gunnar; Spenser, Ian D.
Can. J. Chem. 67, 998-1009 (1989)

Abstract

It is shown by 13C nuclear magnetic resonance spectroscopy that the labelled C2 fragment of <2,3-13C2>pyruvic acid is transferred intact into the C-methyl group and the adjacent carbon atom of the Ephedra alkaloids, norephedrine, ephedrine, norpseudoephedrine, and pseudoephedrine, in growing plants of Ephedra gerardiana. This finding serves to identify pyruvate as the elusive precursor of the aliphatic C2 terminus of the skeleton of the alkaloids.In earlier experiments with 14C-labelled substrates, label from <3-14C>pyruvic acid was incorporated mainly, but not exclusively, into the C-methyl group of ephedrine, and label from <2-14C>pyruvate was incorporated similarly into the carbon atom adjacent to the C-methyl group.A C6-C1 unit related to benzaldehyde or benzoic acid has long been known to generate the benzylic fragment of the carbon skeleton of the Ephedra alkaloids.It is likely that the carbon skeleton of ephedrine is generated from pyruvate and either benzaldehyde or benzoic acid, by a reaction analogous to the formation of acetoin or diacetyl from pyruvate and acetaldehyde or acetic acid, respectively.Key words: biosynthesis of ephedrine, Ephedra alkaloids, 13C NMR spectra, ephedrine, biosynthesis of pyruvic acid, incorporation into ephedrine 13C NMR spectra.

[Teonanacatl]

Also see by the same author:
   Grue-Sorensen, Gunnar and Spenser, I.D. "Biosynthesis of the Ephedra Alkaloids:Evolution of the C6-C3 Skeleton" (1993) JACS 115, 2052.

   Grue-Sorensen, Gunnar and Spenser, I.D. "Biosynthetic Route to the Ephedra Alkaloids" (1994) JACS 116, 6195.

The last (1994) in this list is the most complete of the articles, the other acts merely as an addition to the 89 paper...also:

Catha edulis (khat)produces norpseudoephedrin, which has been shown via 13C and radioactive tracers to be a product of cathinone ((S)-(-)-2-amino-1-phenylpropan-1-one) - another active ingredient of the plant) which derives from 1-phenylpropane-1,2-dione and ultimately from a benzoic acid condensation with pyruvic acid...apparantly it has many effects similar to amphetamine, which is not suprising considering the chemical similarities between these compounds and ampetamine.:
"The chewing of fresh leaves of the khat bush (Catha edulis) is common in certain countries of East Africa and the Arab peninsula, because this material has a stimulating effect. During the last decade, important progress has been made in understanding the pharmacology of this drug. Its actions are mainly due to the alkaloid cathinone, a substance that can be called 'a natural amphetamine'."

- Catha edulis, a plant that has amphetamine effects
      Kalix P
      PHARMACY WORLD & SCIENCE 18(2), 69-73 (1996)

One of the products, cathinone is quite unstable, as fresh Khat(Qat) leaves are the only potent form, they lose their activity when dried:

"Previous studies on the Khat plant (Catha edulis, Celastraceae) illustrated the importance of using freshly harvested young shoots and leaves such that cathinone, the principle active component and Schedule I controlled drug contained within the plant, could be suitably isolated and identified"

- Determination of (S)(-)-cathinone by spectrophotometric detection
   Al-Obaid AM, Al-Tamrah SA, Aly FA, Alwarthan AA
   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS 17(2) 321-326 (1998)

Also, some storage can reduce degredation of cathinone to cathine:

"Upon drying and storage of the cut plant material, cathinone readily converts to the reduced product, cathine, which necessitates rapid extraction and chemical analysis for cathinone identification. This study demonstrates that by air drying the young khat shoots at ambient temperature, cathinone may be detected in khat samples that have been harvested for more than 10 days. Refrigeration for two weeks and freezing for one month of the khat samples also yield identifiable levels of cathinone."

- THE IDENTIFICATION OF CATHINONE IN KHAT (CATHA-EDULIS) - A TIME STUDY
   LEE MM
   JOURNAL OF FORENSIC SCIENCES 40(1), 116-121 (1995)

Effects and Action - I'm not much of a physiologist, so extrapolate what you can from these:

"The leaves of the Qat plant (Catha edulis Forsk., Celastraceae) which contain amphetamine like compounds are widely chewed in Yemen and East Africa for their pleasurable stimulant properties. There are also a number of unwanted side-effects and this paper studies the effect on heart rate and blood pressure in 80 healthy volunteers. During a 3-h period of chewing fresh Qat leaves there was a significant and progressive rise in systolic and diastolic blood pressure and heart rate, and levels had not returned to baseline 1 h after chewing had ceased."

- The effect of Qat chewing on blood pressure and heart rate in healthy volunteers
Hassan NAGM, Gunaid AA, Abdo-Rabbo AA, Abdel-Kader ZY, Al-Mansoob MAK, Awad AY, Murray-Lyon IM
      TROPICAL DOCTOR 30(2), 107-108 (2000)


"The spasmogenic effects of both histamine and carbachol were observed to be antagonized by the khat extract in a concentration-dependent manner. The antispasmodic effect of khat extract was observed to be similar to that of D-amphetamine."

- Constipating and spasmolytic effects of Khat (Catha edulis Forsk) in experimental animals
Makonnen E
PHYTOMEDICINE
7: (4) 309-312 JUL 2000

"The experimental work shows that cathinone is a liable substance, structually related to amphetamine, and similarly to amphetamine, increases the levels of dopamine in the brain by acting on the cathecholaminergic synaspes, Hence the psychostimulant effect of khat can be accounted for by the mechanism of cathinone, which is considered to be its main active ingredient."

- Mechanism of action of cathinone: The active ingredient of khat (Catha edulis)
Patel NB
EAST AFRICAN MEDICAL JOURNAL
77: (6) 329-332 JUN 2000

"It is well established that psychosis may arise in the context of abuse of certain illicit drugs (e.g. amphetamine). This article reviews the effects of chewing the plant khat and outlines the pharmacological aspects,the dependence issue and a comparative study between previously reported cases and four cases reported here to highlight the epidemiology, clinical features and prognosis of khat-induced psychosis"

- KHAT CHEWING AS A CAUSE OF PSYCHOSIS
YOUSEF G, HUG Z, LAMBERT T
BRITISH JOURNAL OF HOSPITAL MEDICINE
54: (7) 322-326 OCT 4 1995


If you're interested in extraction (assuming of course that you do NOT live in a country where cathinone is scheduled and the plant, Catha edulis is illigal (ie NOT the U.S.)) you might want to look at this one:

GC/MS identification of Catha edulis stimulant-active principles
Ripani L, Schiavone S, Garofano L
FORENSIC SCIENCE INTERNATIONAL
78: (1) 39-46 MAR 5 1996


Anyways, enough for now...


Begin with the dissolution of superfluous matters
So that desire and consciousness are free

[Rhodium]

Biosynthetic Route to the Ephedra Alkaloids
Gunnar Grue-Soerensen, Ian D. Spenser

J. Am. Chem. Soc. 116(14), 6195-6200 (1994)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ephedra.alkaloid.biosynthesis-3.pdf)

Abstract

It is shown by ¹³C-NMR spectroscopy that [carboxyl-¹³C]benzoic acid rather than [carbonyl-¹³C,²H]-benzaldehyde supplies the benzylic fragment of the Ephedra alkaloids, norephedrine, ephedrine, norpseudoephedrine, and pseudoephedrine, in growing plants of Ephedra gerardiana sikkimensis. [1,2,3-¹³C₃]-1-Phenylpropane-1,2-dione and (S)-[1,2,3-¹³C₃]-2-amino-1-phenylpropan-1-one ([1,2,3-¹³C₃]cathinone) serve as precursors of the Ephedra alkaloids. (R)- and (S)-[1-¹³C,1-²H]-1-hydroxy-1-phenylpropan-2-one are excluded as intermediates. Cathinone is shown to be a constituent of E. gerardiana.


Biosynthesis of the Ephedra alkaloids: evolution of the C₆-C₃ skeleton
Gunnar Grue-Soerensen, Ian D. Spenser

J. Am. Chem. Soc. 115(5), 2052-2054 (1993)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ephedra.alkaloid.biosynthesis-2.pdf)

[Rhodium]

The biosynthesis of ephedrine
Grue-Sorensen, Gunnar; Spenser, Ian D.

Can. J. Chem. 67, 998-1009 (1989)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/ephedra.alkaloid.biosynthesis-1.pdf)

Abstract
It is shown by ¹³C nuclear magnetic resonance spectroscopy that the labelled C₂ fragment of <2,3-¹³C2>pyruvic acid is transferred intact into the C-methyl group and the adjacent carbon atom of the Ephedra alkaloids, norephedrine, ephedrine, norpseudoephedrine, and pseudoephedrine, in growing plants of Ephedra gerardiana. This finding serves to identify pyruvate as the elusive precursor of the aliphatic C₂ terminus of the skeleton of the alkaloids.In earlier experiments with ¹⁴C-labelled substrates, label from <3-¹⁴C>pyruvic acid was incorporated mainly, but not exclusively, into the C-methyl group of ephedrine, and label from <2-¹⁴C>pyruvate was incorporated similarly into the carbon atom adjacent to the C-methyl group. A C₆-C₁ unit related to benzaldehyde or benzoic acid has long been known to generate the benzylic fragment of the carbon skeleton of the Ephedra alkaloids.It is likely that the carbon skeleton of ephedrine is generated from pyruvate and either benzaldehyde or benzoic acid, by a reaction analogous to the formation of acetoin or diacetyl from pyruvate and acetaldehyde or acetic acid, respectively.

Keywords: biosynthesis of ephedrine, Ephedra alkaloids, ¹³C NMR spectra, ephedrine, biosynthesis of pyruvic acid, incorporation into ephedrine ¹³C NMR spectra.