Synthesis, Structure and Biological Activity of Ephedra Heterocycles (original) (raw)
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Chemical composition of various Ephedra species
The medicinal significance of Ephedra is based on the sympathomimetic properties of ephedrine (E) alkaloids. Pharmacological effects depend on the phytocomposition of individual Ephedra species. The aim of this study was to measure the total alkaloids content (TAC), total phenolics content (TPC), and total flavonoids content (TFC) and determine their relationship in dry herb of Ephedra major, Ephedra distachya subsp. helvetica, Ephedra monosperma, Ephedra fragilis, Ephedra foeminea, Ephedra alata, Ephedra altissima and Ephedra foliata. Nowadays, medicinal use of Ephedrae herba is limited, but the abuse of its psychostimulants is rising. In this study, TAC, TPC and TFC were determined using spectrophotometric methods. For the first time, ultra-performance liquid chromatography with ultraviolet detection (UPLC-UV) was used for separation and quantification of E-type alkaloids of various Ephedra species. The highest TPC and TFC were found in E. alata (53.3 ± 0.1 mg Gallic acid equivalents/g dry weight, 2.8 mg quercetin equivalents/g dry weight, respectively). The total content of E and pseudoephedrine determined by UPLC-UV varied between 20.8 mg/g dry weight (E. distachya subsp. helvetica) and 34.7 mg/g dry weight (E. monosperma). The variable content and ratio between secondary metabolites determined in different Ephedra species reflects their metabolic activities. Utilization of UPLC-UV unveiled that this technique is sensitive, selective, and useful for separation and quantification of different alkaloids in complex biological matrixes. The limit of detection was 5 ng. Application of UPLC-UV can be recommended in quick analyses of E-type alkaloids in forensic medicine and quality control of pharmaceutical preparations.
Two Alkaloids from Ephedra aphylla growing in Egypt
Natural Product …, 2003
The aerial parts of Ephedra aphylla afforded two alkaloids belonging to two different classes. The first alkaloid, ephedradine C, belonging to the spermine alkaloid, a group characterized by its hypotensive effect. The other alkaloid, hordenine is a phenylalkylamine alkaloid isolated for the first time from Ephedra Species. The structures were elucidated by spectroscopic methods and the assignment of some carbons in ephedradine C was achieved based on 2 D-NMR experiments.
Forensic Toxicology, 2018
Purpose Three compounds obtained from ephedrine were identified and characterized by various instrumental analytical methods. Ephedrone (methcathinone) hydrochloride and its fundamental derivatives N-acetylephedrine and N-acetylephedrone were analyzed as precursors of a cathinone derivative. Methods The obtained samples were analyzed by gas chromatography coupled with mass spectrometry, nuclear magnetic resonance spectroscopy, infrared and Raman spectroscopy, and X-ray crystallography. Results The three compounds were confirmed as: N-methyl-2-amino-1-phenylpropan-1-one (methcathinone) hydrochloride, N-acetyl-N-methyl-2-amino-1-phenylpropan-1-one (cathinone derivative), and N-acetyl-N-methyl-2-amino-1-phenylpropan-1-ol (acetyl derivative of ephedrine). Conclusions X-ray crystallography is especially useful for identifying the new designer drugs and their different precursor forms.
Synthesis of new heterocyclics from epoxypulegone
2019
Heterocyclic compounds have been widely used in pharmacology. They play the role of precursors for the synthesis of certain drugs. They also have therapeutic and agri-food properties. In our work, we have prepared heterocycles with different chains by condensation of the different nitrogenous reactants on the epoxypulegone. First, we treated a-ketolpulegone, from the epoxypulegone, and the diastereoisomer (1R, 3R) -3,4'diméthylspiro [cyclohexane-1,2' (1'H)-quinoléine] by m-chloroperbenzoic acid in methylene chloride. We obtained respectively epoxyketol and (1R, 3R)-3,4'diméthylspiro [cyclohexane-1,2' (1'H)-quinoléine] in good yield. On the other hand, we have prepared new benzodiazepine compounds contiguous to the terpene skeleton of pulegone by condensation of orthophenylenediamine and their derivatives on the epoxypulegone. The products obtained were characterized by spectroscopy IR, 1H NMR and 13C NMR.
A systematic approach to quantitation of ephedra alkaloids in natural health products
Analytical and Bioanalytical Chemistry, 2005
A method for accurate determination of ephedrine (E) alkaloids in natural health products (NHP) is described. The NIST dietary supplement standard reference materials (SRMs) were selected for these studies. These SRMs comprise ground Ma Huang herb (Ephedra sinica Stapf.), a spray dried extract of the former, and commercial formulations derived from gel caps and a protein drink. The efficiency of sonication-assisted extraction and Soxhlet extraction was studied using both ammonium formate and potassium phosphate in 3% methanol as extraction media. The efficiency of SPE clean-up of the extract deteriorated rapidly when increasing amounts of sample matrix or analyte were processed, because of limited cartridge capacity. Quantitation by the method of additions was required to ensure the highest accuracy using both LC-UV and ES-LC-MS-MS techniques. Whereas the LC-UV method is more convenient and precise, the results are more questionable than ES-LC-MS-MS, because species-specific detection is not possible.
Chemical and …, 2005
Ephedra, known as Ma huang, is one of the oldest medicinal herbs known to mankind. The genus Ephedra (Ephedraceae) contains more than 50 species. 1) In both traditional and more recent popular uses, the pharmacological effects are mainly attributable to ephedrine-type alkaloids ( ) such as ephedrine, pseudoephedrine, methylephedrine and norephedrine. 2) Although Ephedra sinica has been the primary source for the ephedrine alkaloids or dietary supplements containing Ephedra plant material, other species such as Ephedra equistina, Ephedra intermedia, and Ephedra regelianan contain a certain amount of the ephedrine alkaloids. 3) The concentration of the alkaloids varies from 0.02 to 3.4%. 4) In spite of the variation in the alkaloid content, previous studies related to quality control or chemotaxomic work on Ephedra species were performed focusing on the ephedrine alkaloids. 4-6) To confine the analysis to a small range of metabolites (ephedrine-type alkaloids in the case of Ephedra species) may be misleading in a chemotaxonomic study. For distinguishing the metabolic features of the plant, a broad analysis is demanded. Therefore chemical fingerprinting covering a whole range of metabolites is necessary in order to confirm or deny the plant material being used for the manufacturing of a product. Recently, Schaneberg et al. 7) reported two carboxylic acid derivatives as possible chemical markers in E. sinica detected by HPLC. However, to use the whole "metabolome" of Ephedra and obtain the profile of all metabolites might be more suitable to exclude adulterants or wrong identification.
Total Synthesis and Selective Activity of a New Class of Conformationally Restrained Epothilones
Chemistry - A European Journal, 2008
Stereoselective total syntheses of two novel conformationally restrained epothilone analogues are described. Evans asymmetric alkylation, Brown allylation, and a diastereoselective aldol reaction served as the key steps in the stereoselective synthesis of one of the two key fragments of the convergent synthetic approach.Enzyme resolution was employed to obtain the second fragment as a single enantiomer. The molecules were assembled by esterification, followed by ring-closing metathesis. In preliminary cytotoxicity studies, one of the analogues showed strong and selective growth inhibitory activity against two leukemia cell lines over solid human tumor cell lines. The precise biological mechanism of action and high degree of selectivity of this analogue remain to be examined.
Synthesis and biological evaluation of highly potent analogues of epothilones B and D
Bioorganic & Medicinal Chemistry Letters, 2000
AbstractÐA series of new epothilone B and D analogues incorporating fused hetero-aromatic side chains have been prepared. The synthetic strategy is based on ole®n 3 as the common intermediate and allows variation of the side-chain structure in a highly convergent and stereoselective manner. Epothilone analogues 1a±d and 2a±d are more potent inhibitors of cancer cell proliferation than the corresponding parent epothilones B or D. #
3,4-Dihydroisocarbostyril and 1,2,3,4-tetrahydroisoquinoline derivatives of ephedrine
Journal of Medicinal Chemistry, 1973
Dihydroisocarbostyril and 1,2,3,4-tetrahydroisoquinoline derivatives of ephedrine were synthesized a n d screened for central nervous system activity i n t h e mouse. S o m e of these c o m p o u n d s prevented reserpine ptosis, potentiated &hetamine toxicity, prolonged hexobarbital sleep time, and/or prevented hydrochloric acid writhing in mice. Many heterocyclic derivatives of ephedrine and norephedrine have been synthesized and tested for biological activity. For example, morpholine, 2-oxazoline, oxazolidine, di-and tetrahydro-l,3,4-oxadiazines, 2-thiazoline, thiazolidine, dihydro-l,3 ,4-thiadiazine, tetrahydrous-triazine, and imi-?Chemical Biology Research, The Dow Chemical Company, Midland, Mich. 48640. dazolidine derivatives have been ieported.' Many of these compounds possess interesting biological activity.' For this Derivatives of Ephedrine