SYNTHESIS AND STRUCTURE n-AMINOZILGLYKOZIDES BY THE п-AMINOACETOPHENON

¹O.A. Nurkenov, ¹A.S. Fazylov, ¹Zh.S. Ahmetkarimova, ²R.A. Ermuchanbetova,

¹Zh.B. Satpaeva, ³Zh.H. Muldahmetov

¹Organic synthesis and coal chemistry institute of Republic Kazakhstan,

²Kazakhstan university of friendship of people

³Karaganda state technical university

Now the market of pharmaceutical production is presented to Republics Kazakhstans, basically, on 90 % import medical products that results not only to their significant dearly, but also to direct dependence of deliveries from the countries-exporters. For this reason, at session of 12-congress «Nur Otan» the President of Republic Kazakhstan N.A.Nazarbaev has sounded the program of rise up to the end 2014г. The pharmaceutical industry of Kazakhstan and finishing of the market of production by own medical products up to 50 % from their general number. The main stage of the successful decision of this problem is full integration between many scientists, specializing in the field of organic, bioorganic, pharmaceutical chemistry, pharmacology and medicine. It is the important and multisector problem assumes the organization new original, competitive in the market of domestic medical products which development is conducted on results of fundamental scientific researches in the field of thin organic synthesis, chemistry of natural connections, medicine, technology, etc.

Many medical products because of medicinal resistency of bacteria and viruses gradually lose the efficiency [1,2]. Therefore constant development and introduction of new medical products is an actual problem of a chemistry-pharmaceutical science.

One of perspective directions in search and creation of new medical products is chemical transformation of molecules of known bioactive materials, for example a method glycositical physiologically active connection on carbohydrate center of sugars. Glycositical method usually result ins to decrease in toxicity of substrate and increase in aqueous solubility of drugs. Besides use of a method glycositical will allow to change permeability of physiologically active connections through membranes, and attachment of these connections to oligo-and to polysaccharides will increase life expectancy of medical products [3].

As a result of search of paths of the decision of this problem, employees of Institute of organic synthesis and coal chemistry of Republic Kazakhstan earlier have been carried out researches of interaction of some biogenic heterocyclic amines with carbohydrates, biological activity of the synthesized connections [4,5] is confirmed. With the purpose of continuation of these researches studying reaction glucositical N-aminoacetophenon with monosaccharoses is lead.

Synthesis N-aminoglycosides carried out the known classical method offered on Century by Sorokin in work [6], direct condensation of initial amine with monosaccharoses in a spirit. As a result of the executed researches of condensation of D-glucose, D-galactose and L-arabinose with N- aminoacetophenon it is positioned, that in the environment of absolute ethanol at presence of 1-2 drops of an acetic acid (catalyst) it is possible to achieve a satisfactory yield corresponding aminoglycosides (4-6):

The synthesized glycosides (4-6) are received with a yield of 55-74 %, represent oils light-grow colors sparingly soluble in polar solvents.

In NMR spectra N- aminoglycosides (4-6) it is necessary to note presence of a wide intensive strip in the field of 3405-3520 sm-1, corresponding valence vibrations of hydroxyl groups (IT) of carbohydrates. Presence of several peaks in the field of 1010-1080 sm-1 testify about piranozes to the form glycosidesthe rest.

At the analysis of a spectrum of a nuclear magnetic resonance-1Н (DMSO-d6, 500 MHz) connections (4-6) is positioned, that signals of protons СН-, СН₂- groups a glycosic part of a molecule are displayed in the field of 3,30-3,60 м.d. In the form of a complex multiplet. Anomers proton Н (1) carbohydrate rests is displayed by a triplet at 4,31 м.d. With КССВ = 7,9 Hz, characteristic for b-anomer and testifying to interaction anomer protons not only with the proton next a trance-axial at С₂, but also with amines proton NH, a leaving doublet at 7,1 м.d. Signals of three protons of secondary it-groups of a carbohydrate skeleton are displayed by three doublets at 4,67, 4,7 both 4,73 м.d. And a proton primary it-group a triplet at 4,52 м.d. With КССВ = 5,8 Hz. Methyl protons piperazines cycle are displayed in the form of a singlet in the field of 2,4 м.d. In the field of 6,71-7,75 м.d. Signals protons a benzene ring are marked. The integrated curve corresponds to total of protons.

The table. Physical and chemical constants and data of the element analysis of the synthesized connections (4-6)

Connection	Yield %	Melting point, ^0C	It is found, %			The formula	It is calculated, %
			C	H	N		C	H	N
4	55	225	59,93	9,85	3,88	C18H35NO6	59,81	9,76	3,87
5	70	166	59,93	9,85	3,88	C18H35NO6	59,81	9,76	3,87
6	74	177	61,02	9,55	4,69	C16H29NO5	60,93	9,27	4,44

Thus, condensation of monosaccharoses of D–glucose, L–arabinose and D-galactose with N-aminiacetophenon us for the first time are synthesized and characterized new N-aminoglycosides (4-6), of interest as potential bioactive connections. Composition and a structure new glycopiranozilamines are confirmed by data of the element analysis and IR-spectroscopy.

Experimental part

IR-spectra of connections (4-6) are removed on a spectrometer from the Fourier-converter «AVATAR-320» firms NICOLET in tablets with KBr. Melting points are certain on device " Boetius ". The control over a course of reaction and cleanliness of the received connections carried out a method shallow layer тонкослойной hrommotagraphy on plates «Silufol UV-254» in system isopropyl alcohol-ammonia-water - 7:2:1. A plate displayed in pairs iodine.

N-(-4-acetyphenyl)-b-D-glucopiranozilamine (4). Of 1,21g (0,01 mole) n-aminoacetophenon and 1,8g of D-glucose in 20 ml of absolute ethyl alcohol agitated a mix at temperature 55-60⁰С within 8 hours, have added pair drops of a cold acetic acid. Reactionary weight maintained within day in a freezing case at temperature-18⁰С, formed jelly the rest washed out some times hexane. 1,52g of a derivant piranoziamin (4) in the form of a powder of beige color are received. A yield of 55 %. It is found, %: C 59,93; H 9,85; N 3,88. C₁₈H₃₅NO₆. It is calculated, %: C 59,81; H 9,76; N 3,87. NMR 1Н, м.d., J/Hz: 2,25 with (3Н, СН₃-Аr); 3,30-3,60 m (6Н, (Н2-Н6)); 4,31 t (1Н, Н (1), J-7,9); 6,71 d (1Н, NH, J=7,9); 7,21 d (1Н, Н-Аr-N, J=7,6); 7,75 with (1Н, Н-Аr-СН₃).

N-(-4-acetyphenyl)-b-D-galactopiranozilamine (5) it is received similarly (4). A yield of 70 %. It is found, %: C 59,93; H 9,85; N 3,88. C₁₈H₃₅NO₆. It is calculated, %: C 59,81; H 9,76; N 3,87. NMR 1Н, м.d., J/Hz: 2,25 with (3Н, СН₃-Аr); 3,30-3,60 m (6Н, (Н2-Н6)); 4,31 t (1Н, Н (1), J-7,8); 6,71 d (1Н, NH, J=7,8); 7,21 d (1Н, Н-Аr-N, J=7,6); 7,75 with (1Н, Н-Аr-СН₃).

N-(-4-acetyphenyl)-b-L-arobinopiranozilamine (6). A yield of 74 %. It is found, %: C 61,02; H 9,55; N 4,69. C₁₆H₂₉NO₅. It is calculated, %: C 60,93; H 9,27; N 4,44. NMR 1Н, м.d., J/Hz: 2,35 with (3Н, СН₃-Аr); 3,08-3,67 m (6Н, (Н2-Н6)); 4,56 t (1Н, Н (1), J-7,3); 6,25 d (1Н, NH, J=7,3); 6,81 d (1Н, Н-Аr-N, J=7,1); 7,15 with (1Н, Н-Аr-СН₃).

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