Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук
Циклізацією N2-заміщених 6-бром-3-оксо(аміно)-1,2,4-триазин-5(4Н)-онів з орто-амінотіофенолом одержано і досліджено нову серію трициклічних гетероароматичних сполук. Підтверджено структуру біологічно активних трициклічних глікозидів, нещодавно синтезованих спрощеним методом силільної конденсації, та...
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| Дата: | 2008 |
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Інститут молекулярної біології і генетики НАН України
2008
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| Цитувати: | Трициклическая 1,2,4-триазинсодержащая гетеросистема: направленный синтез новых биологически активных соединений / И.В. Алексеева, Л.И. Пальчиковская, Л.С. Усенко, В.Г. Костина // Біополімери і клітина. — 2008. — Т. 24, № 5. — С. 406-411. — Бібліогр.: 15 назв. — рос., англ. |
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Алексєєва, І.В. Пальчиковська, Л.Г. Усенко, Л.С. Костіна, В.Г. 2019-06-20T20:48:23Z 2019-06-20T20:48:23Z 2008 Трициклическая 1,2,4-триазинсодержащая гетеросистема: направленный синтез новых биологически активных соединений / И.В. Алексеева, Л.И. Пальчиковская, Л.С. Усенко, В.Г. Костина // Біополімери і клітина. — 2008. — Т. 24, № 5. — С. 406-411. — Бібліогр.: 15 назв. — рос., англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.0007B9 https://nasplib.isofts.kiev.ua/handle/123456789/157743 547.863.73:542.953 Циклізацією N2-заміщених 6-бром-3-оксо(аміно)-1,2,4-триазин-5(4Н)-онів з орто-амінотіофенолом одержано і досліджено нову серію трициклічних гетероароматичних сполук. Підтверджено структуру біологічно активних трициклічних глікозидів, нещодавно синтезованих спрощеним методом силільної конденсації, та доведено доцільність і адекватність останнього для направленого глікозилювання триазинвмісних трициклічних основ. A new series of tricyclic heteroaromatic compounds was prepared by cyclization of the 2N-substituted-6-bromo-3-oxo(amino)-1,2,4- triazin-5(4H)-ones with 2-aminobenzothiol. The structure of bioactive tricyclic glycosides, obtained earlier by the simplified silylic method, is confirmed, as well as expedience and adequacy of this method for directed glycosylation of the triazine bearing tricyclic bases. Циклизацией N2-замещенных 6-бром-3-оксо(амино)-1,2,4- триазин-5-онов с орто-аминотиофенолом синтезирована и исследована новая серия трициклических гетероароматических соединений. Подтверждена структура биологически активных трициклических гликозидов, полученных ранее упрощенным методом силильной конденсации, и доказана целесообразность и адекватность использования последнего для направленного гликозилирования триазинсодержащих трицикличных оснований. uk Інститут молекулярної біології і генетики НАН України Біополімери і клітина Біоорганічна хімія Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук Трициклическая 1,2,4-триазинсодержащая гетеросистема: направленный синтез новых биологически активных соединений Tricyclic 1,2,4-triazine bearing heterosystem: directed synthesis of new bioactive compounds Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук |
| spellingShingle |
Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук Алексєєва, І.В. Пальчиковська, Л.Г. Усенко, Л.С. Костіна, В.Г. Біоорганічна хімія |
| title_short |
Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук |
| title_full |
Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук |
| title_fullStr |
Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук |
| title_full_unstemmed |
Трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук |
| title_sort |
трициклічна 1,2,4-триазинвмісна гетеросистема: спрямований синтез нових біологічно активних сполук |
| author |
Алексєєва, І.В. Пальчиковська, Л.Г. Усенко, Л.С. Костіна, В.Г. |
| author_facet |
Алексєєва, І.В. Пальчиковська, Л.Г. Усенко, Л.С. Костіна, В.Г. |
| topic |
Біоорганічна хімія |
| topic_facet |
Біоорганічна хімія |
| publishDate |
2008 |
| language |
Ukrainian |
| container_title |
Біополімери і клітина |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| format |
Article |
| title_alt |
Трициклическая 1,2,4-триазинсодержащая гетеросистема: направленный синтез новых биологически активных соединений Tricyclic 1,2,4-triazine bearing heterosystem: directed synthesis of new bioactive compounds |
| description |
Циклізацією N2-заміщених 6-бром-3-оксо(аміно)-1,2,4-триазин-5(4Н)-онів з орто-амінотіофенолом одержано і досліджено нову серію трициклічних гетероароматичних сполук. Підтверджено структуру біологічно активних трициклічних глікозидів, нещодавно синтезованих спрощеним методом силільної конденсації, та доведено доцільність і адекватність останнього для направленого глікозилювання триазинвмісних трициклічних основ.
A new series of tricyclic heteroaromatic compounds was prepared by cyclization of the 2N-substituted-6-bromo-3-oxo(amino)-1,2,4- triazin-5(4H)-ones with 2-aminobenzothiol. The structure of bioactive tricyclic glycosides, obtained earlier by the simplified silylic method, is confirmed, as well as expedience and adequacy of this method for directed glycosylation of the triazine bearing tricyclic bases.
Циклизацией N2-замещенных 6-бром-3-оксо(амино)-1,2,4- триазин-5-онов с орто-аминотиофенолом синтезирована и исследована новая серия трициклических гетероароматических соединений. Подтверждена структура биологически активных трициклических гликозидов, полученных ранее упрощенным методом силильной конденсации, и доказана целесообразность и адекватность использования последнего для направленного гликозилирования триазинсодержащих трицикличных оснований.
|
| issn |
0233-7657 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/157743 |
| citation_txt |
Трициклическая 1,2,4-триазинсодержащая гетеросистема: направленный синтез новых биологически активных соединений / И.В. Алексеева, Л.И. Пальчиковская, Л.С. Усенко, В.Г. Костина // Біополімери і клітина. — 2008. — Т. 24, № 5. — С. 406-411. — Бібліогр.: 15 назв. — рос., англ. |
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| fulltext |
BIOORGANIC CHEMISTRY
Tricyclic 1, 2, 4-triazine bearing heterosystem: directed
synthesis of new bioactive compounds
I. V. Alexeeva, L. G. Palchikovska, L. S. Usenko, V. G. Kostina
In sti tute of mo lec u lar bi ol ogy and ge net ics NAS of Ukraine
150, Zabolotnogo Str, Kyiv Ukraine, 03680
L.Palchykovska@imbg.org.ua
A new se ries of tricyclic heteroaromatic com pounds was pre pared by cyclization of N2-sub sti -
tuted-6-bromo-3-oxo(amino)-1,2,4-tri azin-5(4Í)-ones with 2-aminobenzothiol. The struc ture of bioactive
tricyclic glycosides, ob tained ear lier by the sim pli fied silylic method, was con firmed as well as ex pe di ence
and ad e quacy of this method for di rected glycosylation of triazine bear ing tricyclic bases.
Keywords: con densed 1,2,4-triazine, tricyclic nucleoside an a logues.
In tro duc tion. The pres ent work is a con tin u a tion of
our study on syn the sis and bi o log i cal prop er ties of a
num ber of de riv a tives of tricyclic heteroaromatic sys -
tem, which con tains bioactive 1,2,4-triazine, to cre ate
com pounds with use ful prop er ties as well as to es tab -
lish the in flu enc ing of struc tural al ter ation on their bi o -
log i cal ac tiv ity.
The com pounds from the 1st se ries (tricyclic
heterobases and their glycosidic de riv a tives) have
shown an ti vi ral ac tiv ity, in par tic u lar, to wards the her -
pes sim plex vi rus type 2 (HSV-2) and Ep stein-Barr vi -
rus [1, 2]. The glycosides have been syn the sized by the
di rect ribosylation of tricyclic heterobases us ing the
silylic method [1].
The aim of this work is to ex tend the range of con -
densed triazine-con tain ing heterosystems us ing an -
other syn thetic ap proach, where triazine frag ment is
rep re sented by N2-alkyl-, N2-tetrahydrofuranyl- and
N2-ribofuranosyl-de riv a tives of
6-bromo-3-oxo(amino)-1,2,4-tri azin-5-one, as a re sult
en sur ing pro duc tion of com pounds with the be fore -
hand pre as signed structures.
Ma te rial and meth ods. The par ent com pounds
for con densed N2-triazine de riv a tives syn the sis -
N2-sub sti tuted
6-bromo-1,2,4-triazine-3,5(2H,4H)-diones (1a, d – f)
as well as 3R-6-bromo-1,2,4-triazine-5(4H)-ones (1b,
c, g) were pro duced by the de scribed meth ods [1, 3 – 6].
Tri ace tate
N2-D-ribofuranosyl-3-amino-6-bromo-1,2,4-triazine-
5-one (1g) was syn the sized by the method [7]. The re -
agents and sol vents from “UkrOrgSyntez” (Ukraine)
and “Fluka” (Swit zer land) were used . The re ac tion be -
hav ior and a pu rity of the com pounds ob tained were
mon i tored by thin-layer chro ma tog ra phy (TLC) on the
plates from “Merck” (Ger many) in the sol vent sys tem
chlo ro form/meth a nol (9:1) (A) or hex ane/ethyl ac e tate
(1:1) (B). The sol vent sys tem isopropanol/to lu ene/am -
mo nium hy drox ide (3:2:1) and con cen tra tion gra di ent
of meth a nol in chlo ro form were used for a pre para tive
chro ma tog ra phy. Ad di tion ally glycosilated de riv a tives
were vi su al ized on TLC us ing a spe cific color re ac tion
406
ISSN 0233-7657. Biopolymers and cell. 2008. vol. 24. N 5. Translated from Ukrainian
© I. V. ALEXEEVA, L. G. PALCHIKOVSKA, L. S. USENKO, V. G. KOSTINA, 2008
with Dishe’s re agent (0.5% so lu tion of cysteine hy dro -
chlo ride in 3N of sul fu ric acid). The 1H-NMR spec tra
were re corded us ing the spec trom e ter “Mer cury-400”
(“Varian”, USA) in DMSO-d6, with tetramethylsilane
as an in ter nal stan dard. The UV-ab sorp tion spec tra
were re corded by the spec trom e ter “Shimdzu
UV-3100” (Ja pan). Melt ing points (M.p.) were de ter -
mined with the Boetius micro melting point apparatus
(Germany).
Chem i cal syn the sis. The de riv a tives of con densed
triazine (Scheme, com pounds 3a-e, ta ble 1) have been
syn the sized by the method, de scribed in the pre vi ous
work [1].
The syn the sis of N2-b-D-ribofuranoside of con -
densed triazine (3f’, 3g’). To a sus pen sion of 1.0 mmol
N2-(2’,3’,5’-tri-0-acetyl)-ribofuranoside of cor re -
spond ing 6-bromo-triazine (1f, 1g) in 5 ml of eth a -
nol/dimethylformamide mix ture were added 0.12 ml
(1.5 mmol) of pyridine and 0.15 ml (1.5 mmol) of
2-aminobenzothiol. The re ac tion mix ture was heated
sev eral hours at 100 0Ñ, mon i tor ing pro cess by TLC.
Af ter a stan dard treat ment the re ac tion mix ture prod uct
(oily) was pu ri fied on the sil ica gel chro mato graphic
col umn. The obtained glycoside tri ace tate was crys tal -
lized from eth a nol. Deacylation of glycoside de riv a -
tives was car ried out for 20 hours with aque ous-al co -
holic solution of ammonia under room temperature.
Physicochemical char ac ter is tics of the glycosides
pro duced are rep re sented in the ta bles 2 and 3.
The syn the sis of
N2-(2’,3’,5’-tri-0-acetyl-b-D-ribofuranosyl)-3-amino-
6-bromo-1,2,4-triazine-5(4H)-one (1g). To the sus pen -
sion of of 3-amino-6-bromotriazine-5(2H)-one (1b)
(900 mg, 2 mmol) and tetraacetylribose ( 700 mg, 2.2
mmol) in 15 ml of ab so lute acetonitrile were added 0.4
ml (3.2 mmol) of trimethylchlorosilane, 0.34 ml (1.6
mmol) of hexamethylsilazane and 0.3 ml (3.2 mmol) of
tin chlo ride. The re ac tion mix ture was stirred in ar gon
at mo sphere un der the room tem per a ture for 4 hours.
De po si tion was re moved, fil trate was va por ized down
to oily res i due. The lat ter was solved in 70 ml of chlo ro -
form, flushed and af ter chlo ro form re moval ap plied
onto the sil ica-gel col umn for chro mato graphic pu ri fi -
ca tion. An a lyt i cally pure acylated N2-glycoside was
ob tained af ter reprecipitation from ethylacetate (the
char ac ter is tics are rep re sented in ta ble 2.)
Re sults and dis cus sion. The con densed
heterocyclic sys tems, based par tic u larly on py rimi -
dines, imidazoles, tri azines, take a sig nif i cant place in
stud ies, ded i cated to the de vel op ment of chem i cal
meth ods for pro duc tion of bioactive polycyclic
heterosystems, re lated to the nat u ral an ti bi ot ics and al -
ka loids, which have antitumor and an ti vi ral ac tiv ity
[8-10] and are also im por tant for the con struc tion of di -
ag nos tic flu o res cence probes [11-14]. Our pre vi ous
work dem on strated that the most ef fec tive pro ce dure
for form ing a lin ear triazine-con tain ing sys tem ap -
peared to be the annelation of 1,2,4-triazine de riv a tives
by 2-aminobenzothiol. Heteroaromatic bases, ob -
tained by this method, were used for the synthesis of
their nucleoside analogs.
The com pounds struc ture was de ter mined by phys -
i cal and chem i cal ap proaches. However, sometimes
the an a lyt i cal char ac ter is tics are not enough to in ter -
407
TRICYCLIC 1, 2, 4-TRIAZINE BEARING HETEROSYSTEM
Scheme. Synthetic route to condensed triazine N2-derivatives
pret un am big u ously the struc tural mod i fi ca tions of
heterosystem , e.g. in the case of its glycosylation.
There fore, this work in ad di tion to ob tain ing novel
com pounds with sub stitu ents in var i ous po si tions of
triazine cy cle was aimed to con firm the ear lier pro -
duced tricyclic glycosides struc tures us ing proper
azanucleosides (1f, g) with fixed po si tion of sugar moi -
ety upon syn the sis.
The choice of com pounds 1a, 1d - f and
3-amino-re placed triazine (1b, c, g) is de ter mined by
the pres ence of two vic i nal electrophylic cen ters (car -
bon at oms in po si tions 5 and 6) in the struc ture of
408
I. V. ALEXEEVA ET. AL.
Compou
nd
Yield,
%
M.p., ( °Ñ)
1Í-NMR ( DMSO-d6 /TMS) d (ppm)
Rf*
Protones of the triazine
ring
Protones of the carbohydrate fragment
N4H NH2
1f 87 70–73
12,73
s(1H) -
6,08 (d, 1H, H-1 , J=3,6 Hz; 5,50 (dd, 1H, H-2 , J=3,5; 3,6 Hz); 5,34
(t, 1H, H-3 ); 4,31 (d, 1H, H-4 ); 4,26 (m, 1H, H-5 ); 4,08 (dd, 1H,
H-5 ); 2,10 (s, 3H, CH3CO-2 ), 2,07 (s, 6H, CH3CO- 3 òà - 5 )
0,31
3f 50 91–93
11,57s(1
H)
-
6,06 (d, 1H, H-1 , J=4,0 Hz); 5,46 (dd, 1Í, Í-2 , J =4,0; 8,0 Hz); 5,32
(m, 1Í, Í-3 ); 4,29 (m, 1Í, Í-4 ); 4,22 (m, 1Í, Í-5 ); 4,06 (m, 1Í,
Í-5 ); 2,09 (dd, 9Í, ÑÍ3ÑÎ- 2 , -3 òà -5 )
0,45
1g 67 82–85 -
7,67
(2Í)
6,04 (d, 1Í, H-1 ,J =2,4 Hz); 5,56 (dd, 1H, H-2 , J= 2,4; 2,0 Hz); 5,33
(t, 1H, H-3 ); 4,32 (m, 1H, H-4 ); 4,27 (m, 1H, H-5 ); 4,08 (m, 1H,
H-5 ); 2,11(s, 3H, CH3CO -2 ); 2,08 (s, 3H, CH3CO -3 ); 2,04 (s, 3H,
CH3CO -5 )
0,39
3g 47 110–112 -
7,23
(2Í)
5,86 (d, 1Í, Í-1 , J =2,0 Hz); 5,47 (dd, 1Í, Í-2 , J =2,4; 2,0 Hz);
5,26 (t, 1Í, Í-3 ); 4,28 (m, 1Í, Í-4 ); 4,11 (t, 1Í, Í-5 ); 4,07 (m, 1Í,
Í-5 ); 2,10 (s, 3Í, ÑÍ3ÑÎ- 2 ); 2,06 (s, 6Í, ÑÍ3ÑÎ- 3 òà -5 )
0,73
* R f in system of solvents: 2-propanol – toluene – 25% NH4OH (3:2:1)
Table 2.
Comparison of physicochemical characteristics of the 1,2,4-triazine tri-0-acetate ribofuranosides and 1,2,4-triazinebearing tricyclic
Compou
nd
Yield,
%
M.p., ( °Ñ)
1Í-NMR ( DMSO-d6 /TMS) d (ppm)
UV, lìàêñ., nm (ethanol)Protones of the triazine ring
Other protons of hetero system
N2H N4H NH2
3a 98 346-350
12,08
s
11,12 s - 7,18 - 6,92 (m, 4Í, Ðh )
208, 240, [269]*,
376
3b 77 295-297 -
-
6,23 s 6,24 - 6,90 (m, 4Í, Ðh ), 10,05 (s, 1Í, NÍ) 213, 242, [303]*, 388
3c 79 250- 253
11,98
s
-
- 7,18 - 7,09 (m, 4H, Ph), 3,19 (s, 6H, ( CH3)2) 219, 254, [303]*, 391
3d 50 315-317
-
11,33 s -
7,10 - 6,98 (m, 4H, Ph), 4,06 (d, 2H, CH2);
2,86 (m, 2H, CH2)
209, 241, [269]*, 386
3e 47 237-239
-
11,31 s -
7,12 - 6,94 (m, 4H, Ph); 6,21 (dd, 1H, Fur);
3,92 - 3,70 (m, 2H, Fur); 2,21- 1,90 (m, 4H,
Fur)
209, 241, [269]*, 385
Protones of cycles: Ph – phenyl, Fur - tetrahydrofuranyl; * - concealed maximum
Table 1.
Physicochemical data of new condensed triazine derivatives 3a - e
triazine heterocycle. These at oms are con sis tently con -
nected with ox y gen and halogen atoms.
The pro cess of con densed triazine for ma tion (as
well as py rim i dine) starts from sub sti tu tion of bro mine
atom for aryl frag ment. The fur ther intramolecular
cyclization of arylation prod uct [6-phenylthio-tri -
azin-3,5(2H,4H)-dione] leads to the ex pected lin ear
sys tem formation [1,8].
Con sid er ing a more pro nounced ar o matic char ac ter
of triazine bases in com par i son with py rim i dine bases
[15], we pre dicted that the syn the sis of con densed sys -
tem to in volve N2-sub sti tuted de riv a tives would not
re quire an ad di tional ac ti va tion of re ac tive cen ters in a
triazine ring and pro ceed with a sat is fac tory yield.
This as sump tion ap peared true only par tially.
The heterosystem for ma tion us ing azanucleosides
(1f, 1g) oc curred with some com pli ca tion be cause of
strict re quire ments for re ac tion, con trary annelation
of non-glycosylated tri azines (1a - e), with for ma tion of
side products.
The pu ri fi ca tion of acylated glycosides and furanyl
de riv a tive of con densed triazine was car ried out by the
col umn chro ma tog ra phy on the sil ica gel with fur ther
crys tal li za tion. The yield made up 45-50%. The com -
pounds 3f, 3g having fixed po si tion of sugar moi ety
were pro duced in this way. The NMR spec tra, cor re lat -
ing with cur rent pro ton sig nals in the spec tra of ini tial
acylglycosides 1f, 1g and tricyclic aglycones 1a, 1b (ta -
ble 1, 2), indicate this definitely.
The most typ i cal are the sig nals of car bo hy drate
frag ment (the lo ca tion of anomeric pro ton and pro ton
sin glet of acetyl groups with to tal in ten sity 9H) and sig -
nals of phenyl nu cleus in re gion 7.0 - 6.8 ppm for both
com pounds. The 3f-com pound is dis tin guished by the
sig nal of cy clic ni tro gen pro ton at triazine ring in re -
gion 11.57 ppm whereas 3g-glycoside is char ac ter is tic
by the pro ton sig nal of exoaminogroup to be located at
7.23 ppm.
An im por tant in for ma tion was also re ceived ow ing
to the analysis of elec tronic ab sorp tion spectra of the
syn the sized com pounds. The ab sorp tion curves of the
un pro tected glycosidic de riv a tives were com pa ra ble
with the same spec tra for the cor re spond ing tricyclic
aglycones thus sug gest ing a weak ef fect of the
glycosidic res i dues on the chromophoric system of
condensed triazines.
The com par i son of ex per i men tally de ter mined
physico-chem i cal and spec tral char ac ter is tics of con -
densed triazine deacylated glycosides (3f ‘, 3g’ ) with
those ob tained via an in de pend ent syn thetic pro ce dure
(tricyclic glycosides IV and VIII [1]) is pre sented in ta -
ble 3. It is worth not ing that col la tion of 1H-NMR
409
TRICYCLIC 1, 2, 4-TRIAZINE BEARING HETEROSYSTEM
Com-po
und
M.p., (?Ñ) 1Í-NMR ( DMSO-d6 /TMS) (ppm)
UV, ìàêñ., nm
(ethanol)
Rf **
²Ó
(ref.1)
236-238
11,36 (s, 1Í, NH); 7,11-7,00 (m, 4Í, Ðh ); 5,86 (d, 1Í, Í-1 ); 4,98 (d, 1Í, ÎÍ-2 );
4,78 (d, 1Í, ÎÍ- 3 ); 4,40 (t, 1Í, ÎÍ- 5 ); 4,15 (dd, 1Í, Í- 2 ); 3,97 (dd, 1Í, Í- 3 );
3,77 (dd, 1Í, Í- 4 ), 3,50 (m, 1Í, Í - 5 ); 3,41 (m, 1Í, Í - 5 );
240, [266]*,
384
0,64
3f ' 236-239
11,18 (br.s, 1H, NH); 7,12-6,99 (m, 4Í, Ðh ); 5,86 (d, 1Í, Í-1 ); 4,98 (dd, 1Í,
ÎÍ-2 ); 4,78 (t, 1Í, ÎÍ- 3 ); 4,40 (m, 1Í, ÎÍ- 5 ); 4,15 (dd, 1Í, Í- 2 ); 3,97 (dd,
1Í, Í- 3 ); 3,77 (dd, 1Í, Í- 4 ), 3,50 (m, 1Í, Í - 5 ); 3,41 (m, 1Í, Í - 5 );
241, [267]*,
385
0,64
Ó²²I
(ref.1)
224-226
7,19 ( br.s, 2H, NH2); 7,10 -6,88 (m, 4H, Ph); 5,46 (d, 1Í, Í-1 ), 5,12 (dd, 1Í,
ÎÍ-2 ), 4,87 (t, 1Í, ÎÍ- 3 ); 4,77 (dd, 1Í, ÎÍ- 5 ); 4,29 (m, 1Í, Í- 2 ); 3,96 (m,
1Í, Í- 3 ); 3,82 (m, 1Í, Í- 4 ); 3,53 (m, 1Í, Í -5 ); 3,46 (m, 1Í, Í -5 )
251,5; [303]*,
383
0,54
3g' 226-228
7,13 ( br.s, 2H, NH2); 7,14 -6,82 (m, 4H, Ph); 5,45 (d, 1Í, Í-1 ), 5,11 (m, 1Í,
ÎÍ-2 ), 4,86 (t, 1Í, ÎÍ- 3 ); 4,76 (m, 1Í, ÎÍ- 5 ); 4,27 (m, 1Í, Í- 2 ); 3,95 (m,
1Í, Í- 3 ); 3,80 (m, 1Í, Í- 4 ); 3,52 (m, 1Í, Í -5 ); 3,44 (m, 1Í, Í -5 )
252, [303]*,
383
0,54
* concealed maximum; ** Rf in system of solvents: n-butanol - acetic acid – water (5:2:3)
Table 3.
Comparison of the physicochemical characteristics of the condensed 1,2,4-triazine N2-b-ribofuranosides have been synthesized by
spec tra re vealed con vinc ing co in ci dence in po si tion
and form for sig nals from car bo hy drate frag ment and
triazine ring of aglicones to in di cate en tire struc tural
identity between compound pairs .
The eval u a tion of other an a lyt i cal properties of
these com pounds let us to claim that all of them have
the struc ture of N2-glycosidic de riv a tives.
The prop o si tion in pa per [1] con cern ing
glycosilation of N5-po si tion in triazine ring was based
on quan tum-chem i cal cal cu la tions for the re ac -
tion-com pe tent nucleofilic cen ters in orig i nal
heterosystem III and sig nif i cant dis crep ancy be tween
1HNMR data and shift of anomeric pro ton in com -
pounds III and IV. Ad di tion ally it should be noted that
prototropic tau tom er ism for a syn the sized tri azin-con -
tain ing com pound re mains un ex plored, but it seems
nec es sary to con sider the avail abil ity of tautomers. The
data of quan tum-chem i cal cal cu la tions dem on strate
that ni tro gen atom charges in N2 and N5 tricyclic sys -
tem po si tions dif fer from the charge at ni tro gen atom
N5 in tiazine ring ex ceed ing that of at ni tro gen atom
(N2) in triazine cy cle. That’s why by anal ogy with
glycosilation of other con densed sys tem de riv a tives
(gua nine and aloxasine) it seems rea son able to sup pose
that N5-glycoside may pres ent a fi nal ki netic prod uct
of the re ac tion, but upon strict syn the sis con di tions in -
volved (~100°C, ac tive cat a lyst, time length) there is
pref er en tially gen er ated the en er get i cally most
advantageous product of thermodynamic control with
glycoside bond in N2-position.
Hence, the over all struc tural iden tity be tween
tricyclic nucleoside sam ples, ob tained by two syn thetic
ap proaches, pro vides ev ery rea son to be lieve that un der
the con di tions of sim pli fied silyl con den sa tion tech -
nique as a ma jor regioisomer the N2-riboside may be
generated.
Pi lot in ves ti ga tion into the syn the sized com pounds
ac tion on HCV replicon (Ph.D. S.L.Rybalko from the
L.V.Gromashevskii In sti tute of Ep i de mi ol ogy and In -
fec tious Dis eases of Acad emy of Med i cal Sci ences of
Ukraine) brought out the ef fec tive in hi bi tion of hep a ti -
tis C vi rus by some con densed triazine de riv a tives at
the level of clinic prep a ra tion, rybavirin. The ma te ri als
of bi o log i cal re search will be pre sented in a sep a rate
publication.
Con clu sion. The us ing of a triazine bases with
fixed substituents at N2- po si tion in clud ing the ribose
res i due too for generating new bi o log i cally ac tive
triazine-bear ing de riv a tives al lows to avoid the prob -
lem of structural un cer tainty in the syn the sized com -
pounds and to provide the functionalization of the
triazine frag ment in tricyclic base in the al ter na tive
way. Such ap proach proved the ad e quacy of the sim pli -
fied silylic con den sa tion for the di rected glycosilation
of tricyclic triazine-bear ing bases.
². Â. Àëåêñººâà, Ë. Ã. Ïàëü÷èêîâñüêà, Ë. Ñ. Óñåíêî, Â. Ã. Êîñò³íà
Òðèöèêë³÷íà 1,2,4-òðèàçèíâì³ñíà ãåòåðîñèñòåìà: ñïðÿìîâàíèé
ñèíòåç íîâèõ á³îëîã³÷íî àêòèâíèõ ñïîëóê
Ðå çþ ìå
Öèêë³çàö³ºþ N2-çàì³ùå íèõ 6-áðîì-3-îêñî(àì³íî)-1,2,4-òðè à -
çèí-5(4Í)-îí³â ç îðòî-àì³íîò³îôå íî ëîì îäåð æà íî ³ äîñë³äæå -
íî íîâó ñåð³þ òðè öèêë³÷íèõ ãå òå ðî à ðî ìà òè÷ íèõ ñïî ëóê.
ϳäòâåð äæå íî ñòðóê òó ðó á³îëîã³÷íî àê òèâ íèõ òðè öèêë³÷íèõ
ãë³êî çèä³â, íå ùî äàâ íî ñèí òå çî âà íèõ ñïðî ùå íèì ìå òî äîì
ñèë³ëüíî¿ êîí äåí ñàö³¿, òà äî âå äå íî äîö³ëüí³ñòü ³ àäåê âàòí³ñòü
îñòàí íüî ãî äëÿ íà ïðàâ ëå íî ãî ãë³êî çè ëþ âàí íÿ òðè à çèíâì³ñíèõ
òðè öèêë³÷íèõ îñíîâ.
Êëþ ÷îâ³ ñëî âà: êîí äåí ñî âà íèé 1,2.4-òðè à çèí, òðè öèêë³÷í³
àíà ëî ãè íóê ëå î çèä³â.
È. Â. Àëåêñååâà, Ë. È. Ïàëü÷èêîâñêàÿ, Ë. Ñ. Óñåíêî,
Â. Ã. Êîñòèíà
Òðèöèêëè÷åñêàÿ 1,2,4-òðèàçèíñîäåðæàùàÿ ãåòåðîñèñòåìà:
íàïðàâëåííûé ñèíòåç íîâûõ áèîëîãè÷åñêè àêòèâíûõ
ñîåäèíåíèé
Ðåçþìå
Öèêëèçàöèåé N2-çàìåùåííûõ 6-áðîì-3-îêñî(àìèíî)-1,2,4-
òðèàçèí-5-îíîâ ñ îðòî-àìèíîòèîôåíîëîì ñèíòåçèðîâàíà è
èññëåäîâàíà íîâàÿ ñåðèÿ òðèöèêëè÷åñêèõ
ãåòåðîàðîìàòè÷åñêèõ ñîåäèíåíèé. Ïîäòâåðæäåíà ñòðóêòóðà
áèîëîãè÷åñêè àêòèâíûõ òðèöèêëè÷åñêèõ ãëèêîçèäîâ,
ïîëó÷åííûõ ðàíåå óïðîùåííûì ìåòîäîì ñèëèëüíîé
êîíäåíñàöèè, è äîêàçàíà öåëåñîîáðàçíîñòü è àäåêâàòíîñòü
èñïîëüçîâàíèÿ ïîñëåäíåãî äëÿ íàïðàâëåííîãî ãëèêîçèëèðîâàíèÿ
òðèàçèíñîäåðæàùèõ òðèöèêëè÷íûõ îñíîâàíèé.
Êëþ÷åâûå ñëîâà: êîíäåíñèðîâàííûé 1,2,4-òðèàçèí,
òðèöèêëè÷åñêèå àíàëîãè íóêëåîçèäîâ.
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