Adekenov, S. M.

English

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Фотосинтез, биохимические процессы, регуляция клеточного метаболизма
38
SESQUITERPENE LACTONES OF PLANTS – PROMISING GROUP OF
NATURAL ISOPRENOID COMPOUNDS
Adekenov S.M.
JSC «International research and production holding «Phytochemistry»», Karaganda,
Republic of Kazakhstan, arglabin@phyto.kz
Isoprenoids take an important place among natural compounds of plants. A promising
group of them is formed by biologically active sesquiterpene γ-lactones having a practical
value as a potential source of new medications. Study of their biological properties re-
vealed many types of activities. Besides, sesquiterpene lactones are important as chemo-
taxonomic markers for solution of complex and confusing problems of systematization and
phylogeny of taxons of various plant families.
Search for raw material, rich by specified sesquiterpene lactones as renewed chemical
material, promotes development of a basis for subsequent synthetic researches directed to
the obtaining of biologically active derivatives of terpenoids. At the same time, finding
new representatives of the series and their physiological estimation enriches existing data-
base for structure-activity relationships studies, which are very important for better effi-
ciency of drug design.
Over 300 species of plants, basically belong to Asteraceae (Compositae) family, were
investigated for the content of sesquiterpene lactones at JSC «International research and
production holding «Phytochemistry»». Presence of sesquiterpene lactones in plant ex-
tracts was defined via absorption band at 1740–1800 cm-1 in IR-spectra that is characteris-
tic for carbonyl γ-lactone group. The extracts were obtained from the plant samples by ex-
traction with chloroform, hot water and ethanol. Extracts were analyzed by HPLC method
with use of authentic markers of sesquiterpene lactones.
Resulting from the screening, 34 species of plants being representatives of genera of Ar-
temisia, Jurinea, Lepidolopha, Phalacrachena, Rhaponticum, Tanacetopsis, Tanacetum
were chosen as perspective sources of sesquiterpene lactones. Additional criterion for final
choice of research objects was availability of raw-material. As a result, 100 sesquiterpene
lactones were isolated and characterized. Twenty six new sesquiterpene lactones were de-
termined in the vegetative objects. It was found that all of them belong to four structural
types – germacranolides, eudesmanolides, guaianolides and pseudo guaianolides. For in-
stance, new sesquiterpene lactones, which have not been described before (1-12), were iso-
lated from Artemisiа subchrysolepis Filatova, Ajania fruticulosa (Ldb.) Poljak., Tanacetum
vulgare L., Artemisia tournefortiana Rchb., Artemisia filatovii A.Kuprijanov sp. Nova,
Rhaponticum serratuloides (Georgi.) Bobr. and Artemisia leucodes Schrenk. Their struc-
tures were determined by spectral methods, including X-ray analysis, and by chemical
conversions.
For the first time reactions of acidolysis, bromination, amination, alkylation, oxidation,
and rearrangement were carried out on epoxy-group of sesquiterpene lactones. 600 deriva-
tives were synthesized and their bioscreening was carried out. Structure of modified com-
pounds was determined on the basis of their physical and chemical constants, data of ele-
ment analysis, IR-, UV-, mass-, NMR 1H, 13С- spectra, two-dimensional NMR spectros-
copy 1Н-1Н, 13С-1Н, HPLC and X-ray analysis.
Фотосинтез, биохимические процессы, регуляция клеточного метаболизма
39
O
OH
AcO
O
O
O
O
OH
H
O
O
AcO
O
O
HO
H
AcO
H
H
OC
O Cl
OH
O
O
HO
HO
HO
H
H
OC
O
HO
8
10
O
O
HO
H
HO
H
H
OC
O Cl
OH
O
O
HO
HO
AcO
H
H
OC
O
9 12
O
O
O
O
O
O
H
11
7
O
O
HO H OH
HO
O
O
O H
OH
O
O
O
H
1 2 3 4
5 6
OAc OAc
HO
HO
As a result of the investigations, it was established that endemic Central Kazakhstan
plant Artemisia glabella Kar. et Kir. is a source of sesquiterpene lactone arglabin, which
has not been described before. The lyophilized dosage form for parenteral injection of
preparation «Arglabin», possessing high antitumor, radio-sensitizing and immuno-
modulating activity was developed on the basis of chemically modified derivative arglabin.
Another innovative product is the original hypolipidemic preparation «Aterolid» of
plant origin based on guaiane sesquiterpene lactone leucomisin isolated from Artemisia
leucodes Schrenk.
Pre-clinic studies showed good prospects for development of new preparation «Sau-
salin» for treatment of parasitosis of hepatobiliary system based on the sum of sesquiter-
pene lactones from Saussurea salsa (Pall.) Spreng.
A new method for isolation of sesquiterpene lactones arglabin, leucomisin and achillin
from raw material was developed. It includes preparative centrifugal partition and prepara-
tive high-performance liquid chromatography. The advantage of this method is high pro-
ductivity, absence of toxic solvents, full automation and significant reduction of process
duration.
Thus, results on isolation and determination of structure of sesquiterpenoids from plants
of Kazakhstan, chemical modification directed to the synthesis of new physiologically ac-
tive derivatives of these natural compounds, are the prerequisite for development of the
effective preparations possessing wide spectrum of pharmacological action for medicine.


Sesquiterpene lactones of plants – promising group of natural isoprenoid compounds

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Sesquiterpene lactones of plants – promising group of natural isoprenoid compounds

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