SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES

Authors

  • M. I. Romanenko
  • M. V. Nazarenko
  • D. G. Ivanchenko
  • O. A. Pakhomova
  • A. Yu. Cherchesova

DOI:

https://doi.org/10.14739/2409-2932.2014.3.32844

Keywords:

xanthine, organicsynthesis, NMR-spectroscopy

Abstract

Introduction

It has been foundearlier[1-5]that 8-substituted of 7-(2-hydroxy-3-R-oxypropyl-1)-3-methylxanthine show rather high diuretic, anti-inflammatory, analgesic, antioxidant and hypolipidemic action.Meanwhile, works of international researchers reveal data on synthesis of other equivalents of7-(2-hydroxy-3-R-propyl-1)-xanthine, which demonstratebroncholytic, antiasthmatic and antianaphylacticeffects[6-8] and can be used as anti-inflammatory medicines[9].

The aim of this work is to develop unique methods for synthesizing8-aminoderivativesof 7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthines, the potential bioactive compounds yet undescribed in scientific works, and to study their physical and chemical peculiarities.

Materials and Methods of Research

Themeltingpointhasbeendeterminedwiththehelpofanopencapillary methodwithTAPdevice(M).Elementalanalysishasbeenperformedwiththe help of the instrument ElementarVario L cube, NMR-spectra have been taken on a spectrometer Bruker SF-400 (operating frequency of 400 MHz, solvent DMSO-d6, internal standard – TMS).These data correspond to thecalculated elemental analysis.

Results and their discussion

Similarly to the method of synthesizing 7-(3-aryloxy-2-hydroxypropyl-1)-8-bromoxanthines[11], described earlier,8-bromo-7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthine, undescribed before(2) (scheme 1) was synthesized through the reaction of 8-bromo-3-methylxanthine(1) [10] with isopropoxymethyloxirane in butanol-1in the presence of N,N-dimethylbenzylamine.

The presence of a substitute in position 7 of molecule of 8-bromo-3-methylxanthine, and the data of PMR-spectroscopy only attest to the fact that obtained bromalcohol (2) in contrast to the initial compound (1) is not dissolvedat room temperature in water solution of ammonia.

Presence of bromine atom in position 8 allows to put in variousO-, N-, S-containing substitutes in xanthine molecule and consequently expect to see changes and manifestation of a certain biological effect in obtained derivatives.

It has been found that short-period boiling of bromalcohol (2) with primary amines in water or waterdioxaneleads to a formation of relevant 8-aminosubstituted 7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthine(3-12). The structure of synthesized aminalcohols 3-12 has been proved based on their PMR spectra analysis.

Conclusions

For further synthetic research, along with convenient synthones there have also been elaborated easy-to-apply laboratory methods for synthesizing8-amino-7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthines, which are potential bioactive compounds.

The structure of synthesized compounds has been proved by elemental analysis, IR- and NMR-spectroscopydata. 

References

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How to Cite

1.
Romanenko MI, Nazarenko MV, Ivanchenko DG, Pakhomova OA, Cherchesova AY. SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES. Current issues in pharmacy and medicine: science and practice [Internet]. 2014Nov.12 [cited 2024Jun.21];(3). Available from: http://pharmed.zsmu.edu.ua/article/view/32844

Issue

Section

Pharmacognosy and chemistry of natural compounds