SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES
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...
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2014-12-01
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doaj-a816f04bc6764b2da6fbec54786319f22020-11-25T01:05:37ZengZaporozhye State Medical UniversityAktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki2306-80942409-29322014-12-013363910.14739/2409-2932.2014.3.32844SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINESM. I. RomanenkoM. V. NazarenkoD. G. IvanchenkoO. A. PakhomovaA. Yu. CherchesovaIntroduction 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. http://pharmed.zsmu.edu.ua/article/view/32844/29458xanthineorganicsynthesisNMR-spectroscopy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
M. I. Romanenko M. V. Nazarenko D. G. Ivanchenko O. A. Pakhomova A. Yu. Cherchesova |
spellingShingle |
M. I. Romanenko M. V. Nazarenko D. G. Ivanchenko O. A. Pakhomova A. Yu. Cherchesova SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki xanthine organicsynthesis NMR-spectroscopy |
author_facet |
M. I. Romanenko M. V. Nazarenko D. G. Ivanchenko O. A. Pakhomova A. Yu. Cherchesova |
author_sort |
M. I. Romanenko |
title |
SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES |
title_short |
SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES |
title_full |
SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES |
title_fullStr |
SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES |
title_full_unstemmed |
SYNTHESISAND PHYSICAL-CHEMICAL PROPERTIES OF 8-AMINO-7-(2-HYDROXY-3-i-PROPOXYPROPYL-1)-3-METHYLXANTHINES |
title_sort |
synthesisand physical-chemical properties of 8-amino-7-(2-hydroxy-3-i-propoxypropyl-1)-3-methylxanthines |
publisher |
Zaporozhye State Medical University |
series |
Aktualʹnì Pitannâ Farmacevtičnoï ì Medičnoï Nauki ta Praktiki |
issn |
2306-8094 2409-2932 |
publishDate |
2014-12-01 |
description |
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.
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topic |
xanthine organicsynthesis NMR-spectroscopy |
url |
http://pharmed.zsmu.edu.ua/article/view/32844/29458 |
work_keys_str_mv |
AT miromanenko synthesisandphysicalchemicalpropertiesof8amino72hydroxy3ipropoxypropyl13methylxanthines AT mvnazarenko synthesisandphysicalchemicalpropertiesof8amino72hydroxy3ipropoxypropyl13methylxanthines AT dgivanchenko synthesisandphysicalchemicalpropertiesof8amino72hydroxy3ipropoxypropyl13methylxanthines AT oapakhomova synthesisandphysicalchemicalpropertiesof8amino72hydroxy3ipropoxypropyl13methylxanthines AT ayucherchesova synthesisandphysicalchemicalpropertiesof8amino72hydroxy3ipropoxypropyl13methylxanthines |
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