V. V. Grishko

SYNTHESIS OF LUPANE AND 19β,28-EPOXY-18α-OLEANANE 2,3-seco-DERIVATIVES BASED ON BETULIN

The α-hydroxyoximes of methyl betulonate and allobetulone were synthesized. Beckmann fragmentation of them produced the lupane and 19β,28-epoxy-18α-oleanane 2,3-seco-derivatives.

Synthesis and antiviralactivity of 2,3-seco-derivatives of betulonic acid

A lupane 2,3-seco-aldehydoacid that was oxidized further to the 2,3-seco-diacid was synthesized by Beckmann fragmentation of the α-hydroxyoxime of betulonic acid. It was found that both 2,3-seco-derivatives were capable of suppresing reproduction of Herpes type 1 and flu A viruses (EC50 from 1.9 to 21.3 μM).

Triterpenoids with a Five-Membered a-Ring: Distribution in Nature, Transformations, Synthesis, and Biological Activity

The literature on the distribution in nature, structural variations, isolation, identification, and biosynthesis issues of triterpenoids with a five-membered A-ring was reviewed. The principal trends in approaches to the synthesis of structural analogs of such compounds were discussed. Information on the biological activity of natural and semi-synthetic A-pentacyclic triterpenoids was presented.

Antiviral activity of 2,3-secotriterpenic hydrazones of the lupane and 19β,28-epoxy-18α-oleanane types

Novel hydrazones of the lupane and 19β,28-epoxy-18α-oleanane types have been synthesized via the interaction of 2,3-secotriterpenic aldehydonitriles with substituted hydrazines. As a result of the investigation of the antiviral activity of 2,3-secotriterpenic hydrazones against the Indiana strain of the vesicular stomatitis virus on two models of mammalian cell line infection, the acetylhydrazone of 1-cyano-2,3-seco-19β,28-epoxy-18α-olean-3-al has been found to have a high prophylactic activity of 0.00016 μg/ml to the vesicular stomatitis virus and to inhibit virus reproduction in primarily infected cells in a 0.21-μg/ml concentration.

ANTI-INFLAMMATORY ACTIVITY OF ISOBORNYLPHENOL DERIVATIVES

Nonsteroidal anti-inflammatory drugs and non-narcotic analgesics are widely used to treat various inflammatory diseases of infectious and noninfectious nature [1]. The development of new drugs based on terpenophenols, which have a unique set of pharmacological properties [2], is highly promising. The literature teaches that phenols with a bicyclic isobornyl moiety exhibit anti-infection activity [3]. The series of studies performed by us on the synthesis and investigation of terpenophenols showed that some alkylphenols exhibit hemorheological properties and improve brain blood flow [4, 5]. Thus, the synthesis of terpenophenols is critical for further studies of their physiological properties. Herein we present results from a study of the anti-inflammatory activity of the synthesized terpenophenols and their aminomethyl derivatives. A series of isobornylphenols (1a–e) with various substituents in the aromatic ring were prepared earlier via alkylation of phenols by the natural monoterpenoid camphene in the presence of the corresponding aluminum phenolates [6–8].

Synthesis of A-Pentacyclic Triterpene α,β-Alkenenitriles

A-seco-triterpenoids with a methylketone group were synthesized from epimeric 3-hydroxy-3-methyl-1-cyano-2,3-seco-triterpenoids of the lupane and 19β,28-epoxy-18αH-oleanane types, which were formed by a Grignard reaction. The resulting methylketones underwent under base-catalysis conditions an intramolecular cyclization to form A-pentacyclic β-substituted alkenenitriles. The synthesized compounds included 3-methyl-1-cyano-19β,28-epoxy-2,3-seco-2-nor-18αH-olean-3-one and methyl 3-methyl-1-cyano-2-norlup-1(3),20(29)-dien-28-oate, which inhibited in vitro reproduction of human immunodeficiency virus type 1.

Synthesis and biological activity of mono- and diamides of 2,3-secotriterpene acids

Amides of four types were synthesized derived from 2,3-seco-18αH-oleanane and 2,3-secolupane mono- and dicarboxylic acids. The spectrum of diamide derivatives was expanded with C3-C3′ and C28-C28′ biscondensed amides with two A-secotriterpene backbones obtained by the interaction of monocarboxylic A-seco acids with lysine. Among the synthesized monoand diamide derivatives, potential inhibitors of herpes simplex virus type 1 replication were found, namely, some compounds with an ethyl β-alaninate fragment (EC50 8.7 and 4.1 μM). The ethyl β-alaninate diamide was shown to combine antiherpetic and anti-HIV activity (EC50 5.1 μM). For the active compounds, the ratios of maximum tolerable concentrations to EC50 ranged from 9.7 to 40.8. The synthesized amides did not show any marked cytotoxic effects against human rabdomiosarcoma RD TE32, A549 lung carcinoma, and melanoma MS cell lines.

The immunotropic activity of lupane and oleanane 2,3-seco-triterpenoids

The immunotropic effect of the 2,3-seco derivatives of allobetulon, betulonic acid, and the methyl ester of betulonic acid were studied. It was found that the highest activity is shown by compounds with an oleanane fragment. The presence of a free C28-carboxyl group enhances the activity of lupane 2,3-seco derivatives. A significant contribution to the development of the immune response is introduced by a functional group at the C3 atom in the A ring—the C3-carboxy derivatives intensify the processes of antibody production and alter the number and ratio of leukocyte forms. It is shown that 2,3-seco-1-cyano-19β,28-epoxy-18α-olean-3-oic acid stimulates humoral immunity with a positive influence on hematopoiesis.

The synthesis of triterpenic amides on the basis of 2,3-seco-1-cyano-19β,28-epoxy-18α-oleane-3-oic acid

Novel 2,3-seco-triterpenic amides were prepared by the interaction of the chloride of 1-cyano-19β,28-epoxy-18α-oleane-3-oic acid with primary amines and synthetic and biogenic amino acids. A cytotoxic triterpenic conjugate with a residue of the ethyl ester of β-alanine was found among the synthesized nitrogen-containing derivatives. Treatment with this conjugate in a concentration of 100 μM resulted in the 45.5% survival of melanoma cells in the medium.

18-Succinyloxyabieta-8,11,13-triene as a new component from green shoots of the Siberian fir

A new diterpene derivative, 18-succinyloxyabieta-8,11,13-triene, was isolated from the acidic fraction of the extract from wood greens of a Siberian fir. The chemical structure of the molecule was established on the basis of spectroscopy and confirmed by partial synthesis from abieta-8,11,13-trien-18-ol.