Krystyna Wojtasiewicz

Identification and synthesis of some contaminants present in 4-methoxyamphetamine (PMA) prepared by the Leuckart method

The clandestine synthesis of ring and side chain modified phenylisopropylamines continues to be a major source of these drugs of abuse. One method used for the synthesis of the amphetamine and related compounds involves the treatment of the appropriate ketone with formamide or ammonium formate followed by acid hydrolysis of intermediate N-formyl derivative. In this paper the synthesis of 4-methoxyamphetamine (PMA, 1) by the Leuckart method is investigated. The identification by means of gas chromatography-mass spectrometry (GC-MS) of methoxy derivative of N-(beta-phenylisopropyl)benzaldimine 9, methoxy derivative of N-(beta-phenylisopropyl)benzyl methyl ketimine 5, 1-(4-methoxyphenyl)-N-(4-methoxybenzyl)-2-propanamine 10, (RR/SS) and (RS) 1-(4-methoxyphenyl)-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 6a-6c, (RR/SS) and (RS)-1-(4-methoxyphenyl)-N-methyl-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 7a-7c, (RR/SS) and (RS)-1-(4-methoxyphenyl)-N-formyl-N-[2-(4-methoxyphenyl)-1-methylethyl]-2-propanamine 8a-8c in crude PMA, are reported. The identity of these compounds was confirmed by independent synthesis of reference compounds. The NMR, MS, IR data, stereochemistry and some chromatographic properties of synthesized compounds are discussed. Finally, the results of the GC-MS analysis of illicitly prepared tablets, containing PMA 1 and 4-methoxymethamphetamine (PMMA, 2), are outlined. The presence of 4-methoxydimethylamphetamine 11, 4-methoxyethylamphetamine 12, and 4-hydroxymethamphetamine 13 are reported in these tablets. The identity of 2, 11, and 12 was confirmed by their independent synthesis.

α-Phenylethylamine in illegally produced amphetamine

The possibility of simultaneous synthesis of α-phenylethylamine and amphetamine from mixture of acetophenone and benzylmethylketone was studied. The structures of specific impurities were predicted and these compounds were synthesized and finally found in reaction mixtures, as well as in the final product. The data collected by gas chromatography, proton and carbon magnetic resonance, Fourier transform infrared spectrometry and mass spectrometry are presented.

Sulphoxides of thiobinupharidine thiohemiaminals from Nuphar lutea

Abstract From the rhizomes of Nuphar lutea four new alkaloids were isolated. Their structures were established as syn-6-hydroxythiobinupharidine sulphoxide, syn-6′-hydroxythiobinupharidine sulphoxide, syn-6,6′-dihydroxy thiobinupharidine sulphoxide and anti-thiobinupharidine sulphoxide.

Stereoselective synthesis of (R)-(−)-mianserin

Abstract (14bR)-2-Methyl-1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine, (R)-(−)-mianserin 1a was synthesised in several steps in good enantiomeric purity with the use of (S)-(−)-α-methylbenzylamine 5. The absolute configuration was assigned on the basis of X-ray data.

The oxidation products of melatonin derivatives exhibit acetylcholinesterase and butyrylcholinesterase inhibitory activity

Abstract:  It is already well documented that melatonin exhibits strong antioxidant properties. It traps several reactive oxygen species including singlet oxygen, peroxyl and hydroxyl radicals. Also, peroxynitrite‐induced reactions are inhibited by melatonin. The oxidation of melatonin by singlet molecular oxygen [O2 (1Δg)] may produce cyclic 3‐hydroxymelatonin whose structure we have already studied. In this investigation we report on the synthesis of several melatonin analogues having a carbamate substituent instead of the methoxy group at 5 position of the indole ring. These compounds behave analogously to melatonin with respect to singlet oxygen and produce the corresponding cyclic 3‐hydroxymelatonin analogues. The structures of the products were investigated with spectral methods and X‐ray crystallography. The compounds obtained possess the 2,3,8,8a‐tetrahydropyrrolo[2,3‐b]indole heterocyclic system which is a structural motif characteristic of alkaloids, physostigmine and phenserine, that are potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors used in the Alzheimer’s disease treatment. We measured the inhibitory activity of the obtained compounds against AChE and BChE from human erythrocytes and serum. In the case of the compounds having a phenylcarbamate and methoxyphenylcarbamate substituents, the inhibitory activity (IC50) ranged from 0.252 ± 0.033 to 3.804 ± 0.581 μm. Other compounds were less active and showed rather complex interactions with the structure–activity relationship in need of further investigation.

Nuphacristine—an alkaloid from Nuphar luteum

Abstract From the rhizomes of Nuphar luteum a new C 15 alkaloid, nuphacristine, has been isolated. The structure and stereochemistry of nuphacristine have been established on the basis of spectral analysis and chemical transformations.

The analytical profile of some 4-methylthioamphetamine (4-MTA) homologues

The 4-methylthioamphetamine (4-MTA) is a sulphur-containing amphetamine-type stimulant (ATS), which appeared on the illicit market in Europe at the end of 90s. For the purpose of this study, several N-alkyl homologues of 4-MTA, including 4-methylthiomethamphetamine (4-MTMA), 4-methylthioethylamphetamine (4-MTEA), 4-methylthiodimethamphetamine (4-MTDMA), 4-methylthiopropylamphetamine (4-MTPA) and 4-methylthiobutylamphetamine (4-MTBA) were synthesized. The homologues were characterized by means of gas chromatography/mass spectrometry (GC-MS), infrared (IR) spectroscopy and the magnetic resonance spectroscopy ((1)H and (13)C NMR). The gas chromatography and mass spectrometry properties of their acetyl, trifluoroacyl (TFA), pentafluoropropionyl (PFP) and heptafluorobutyryl (HFB) derivatives were also investigated and discussed.

Methiodides of nuphar alkaloids: Part I. Studies on stereochemistry by carbon-13 nuclear magnetic resonance spectra of some thiospirane C30 and C15 methiodides

Abstract The 13 C NMR spectra of deoxynupharidine, 7-epideoxynupharidine and thiobinupharidine methiodides have been studied and the correlations between the stereochemistry of these compounds and corresponding chemical shifts are described. Quaternization of the nitrogen causes no steric changes in the trans -quinolizidine system of 7-epideoxynupharidine, whereas deoxynupharidine methiodide has a transformed quinolizidine system with cis ring fusion. Quaternization of thiobinupharidine with methyl iodide results in two isomeric monomethiodides which have been characterized as A′-B′- trans and AB- trans isomers of quaternary salts.

The synthesis and the structure elucidation of N,O-diacetyl derivative of cyclic 3-hydroxymelatonin

Melatonin was subjected to an oxidation to give 3-hydroxymelatonin. All spectroscopic data for this compound were collected. Ab initio calculations for both possible configurations were performed. X-ray data on N,O-diacetyl derivative of 3-hydroxymelatonin allowed the unambigous structure determination.

Unprecedented racemization of (S)-(+)-naproxen during a BOP-mediated esterification. X-Ray structures of diastereomeric esters

Abstract During esterification of enantiomerically pure (S)-(+)-naproxen under mild conditions with the use of the BOP-reagent, a complete racemization was observed.