ISSN 1070-4272, Russian Journal of Applied Chemistry, 2006, Vol. 79, No. 4, pp. 654!659. + Pleiades Publishing, Inc., 2006.
Original Russian Text + A. D. Zorina, L. V. Balykina, O. V. Nazarova, A. A. Rebezov, 2006, published in Zhurnal Prikladnoi Khimii, 2006, Vol. 79,
No. 4, pp. 663!668.
AND POLYMERIC MATERIALS
Polymeric Derivatives of Dipterocarpol,
a Dammarane Triterpenoid
A. D. Zorina, L. V. Balykina, O. V. Nazarova, and A. A. Rebezov
St. Petersburg State University, St. Petersburg, Russia
Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, Russia
Received December 26, 2005
Abstract-Polymeric derivatives of dammarane triterpenoids with both labile and strong (covalent) poly-
mer3triterpenoid bonds were prepared from N-vinylpyrrolidone copolymers.
Treatment of virus diseases requires development
of effective nontoxic antiviral preparations. Synthesis
of polymeric derivatives of low-molecular-weight
biologically active substances (BASs) opens prospects
for development of improved medicinals of reduced
toxicity, enhanced efficiency, and prolonged effect.
Polymers based on N-vinylpyrrolidone (VP) are
among the most widely used polymeric carriers [1, 2].
VP copolymers containing amino groups show prom-
ise as BAS carriers. Alkylation with various alkyl
halides of VP copolymers with primary and tertiary
amines allows preparation of polymers containing,
along with the ionic ammonium group, alkyl substitu-
ents providing hydrophobic interaction in aqueous
solutions . Preparation of water-soluble derivatives
(salts) of polyene antibiotics Levorin and Nystatin on
the basis of such copolymers was reported in .
Previous studies revealed more pronounced anti-
viral properties of polymeric derivatives of certain tri-
terpene acids compared to the nonmodified acids .
The goal of this study was to develop procedures
for preparing from VP copolymers polymeric deriva-
tives of triterpenoids of the dammarane series differ-
ing in the type and lability of the polymer3triterpenoid
Among dammarane triterpenoids, the highest anti-
viral activity is exhibited by alnincanone, 24-methyl-
20S,24R-epoxydammaran-3-one ; however, its
content in plant sources is insufficient for more com-
prehensive biological studies. As a model compound
we chose 20(S)-hydroxydammar-24-en-3-one (diptero-
carpol) I. It can be prepared in amounts required for
the studies from Dipterocarpus alatus latex .
We prepared dammarane derivatives containing at
C-17 an open chain (VII), a g-lactone ring (III), and
a tetrahydrofuran ring (IV). Diol VII was prepared by
reduction of dipterocarpol with sodium borohydride in
ethanol. To prepare compounds III and IV, diptero-
carpol was oxidized with chromic anhydride in acetic
acid to lactone II. Reduction of II with sodium boro-
hydride in ethanol yielded hydroxy lactone III, and
reduction with sodium borohydride in the presence of
in THF yielded epoxydammaranol IV.
From compounds III, IV, and VII (Scheme 1) con-
taining the 3b-hydroxy group, we prepared by reflux-
ing with phthalic anhydride phthalic acid monoesters
V, VI, and VIII, respectively (Scheme 1). Through
the free carboxy group, these compounds were bonded
to an amino group of the polymer.
To prepare polymeric derivatives of triterpenoids
of the dammarane series with a labile BAS3polymer
bond (BAPs), we used a copolymer of VP with di-
methylaminoethyl methacrylate (DMAEM) and with
its derivative quaternized with dodecyl iodide
(DMAEM . C
I) . Polymeric salts of phthalic
acid monoesters were prepared by Scheme 2.
As solvent we used methanol in which all the re-
actants (triterpenoid hydrogen phthalates and the poly-
mer) and products (polymeric salts) are soluble. After
the synthesis completion, methanol was gradually
replaced by water . As a result, we obtained poly-
meric derivatives which, in contrast to the starting