Russian Journal of Bioorganic Chemistry, Vol. 29, No. 6, 2003, р . 594

Synthesis and Antiviral Activity of Ureides and Carbamates of Betulinic Acid and Its Derivatives

O. B. Flekhter*, ¹ E. I. Boreko**, L. R. Nigmatullina*, E. V. Tret’yakova*, N. I. Pavlova**, L. A. Baltina*, S. N. Nikolaeva**, O. V. Savinova**, F. Z. Galin*, and G. A. Tolstikov*

*Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Russia, **State Research Institute of Epidemiology and Microbiology, Minsk, Belarus

Abstract: Ureides and carbamates of betulinic acid and its derivatives were prepared in good yields by interaction of betulinic acid, betulonic acid, and betulonic acid 3-oxime with amines, amino acids, and alcohols. Ureides of betulonic acid containing L-Val and L-Met residues were found to be effective against herpes simplex type 1 virus.

Key words: antiviral activity; betulinic acid, isocyanates, carbamates, ureides; lupane triterpenoids

Russian Journal of Bioorganic Chemistry, Vol. 29, No. 6, 2003, р . 601

Transformations of Glycyrrhizic Acid: XV. ¹ Synthesis of Triterpene Saponins with Monosaccharide Residues Attached through Ester Bonds

R. M. Kondratenko*, L. A. Baltina*, ² S. R. Mustafina*, E. V. Vasil’eva*, A. F. Ismagilova**, N. G. Vasil’eva**, and G. A. Tolstikov*

*Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Russia, **Bashkir State Agricultural University, Ufa, Russia

Abstract: Triterpene saponins, glycoside analogues of glycyrrhizic acid with a modified carbohydrate chain containing monosaccharide residues attached through ester bonds, were synthesized. To this end, peracetylated glycyrrhizic acid or its 30-methyl ester were glycosylated by 2,3,4,6-tetra-O-acetyl--D-gluco- or --D-galac-topyranosyl bromide in dichloroethane in the presence of Ag₂CO₃. Glycerrhetinic acid saponin with D-Galp residues exhibited a higher antiulcer activity than glycyrrhizic acid in rats at a dose of 25 mg/kg.

Key words: antiulcer activity, glycyrrhizic acid, triterpene saponins

Russian Journal of Bioorganic Chemistry, Vol. 30, No. 1, 2004, р . 53

Synthesis and Immunostimulating Activity of Cysteine-Containing Derivatives of Glycyrrhizic Acid

R. M. Kondratenko**, L. A. Baltina*, ¹ E. V. Vasil’eva*, L. A. Baltina (Jr.)**, A. F. Ismagilova*, Kh. M. Nasyrov*, ^† N. Zh. Baschenko**, R. M. Kireeva**, S. M. Fridman**, and G. A. Tolstikov*

*Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, Bashkortostan, 450054 Russia, **Bashkortostan State Medical University, Ufa, Bashkortostan, 450074 Russia

Abstract: New cysteine-containing derivatives of glycyrrhizic acid were synthesized by its coupling with Cys(Bzl) esters or the Cys(Bzl)-Val-OBu ^t dipeptide by the active ester method (DCC/HOSu) or by Woodward’s reagent K. The derivatives with Cys(Bzl) and Cys(Bzl)-Val residues attached to the carbohydrate part of the molecule stimulated the primary immune response and the reaction of delayed-type hypersensitivity in mice at a dose of 2 mg/kg.

Key words: cysteine, glycopeptides, glycyrrhizic acid, immunostimulating activity, synthesis

Russian Journal of Bioorganic Chemistry, Vol. 30, No. 1, 2004, р . 80

Synthesis and Antiviral Activity of Betulonic Acid Amides and Conjugates with Amino Acids

O. B. Flekhter*, ¹ E. I. Boreko**, L. R. Nigmatullina*, E. V. Tret’yakova*, N. I. Pavlova**,L. A. Baltina*, S. N. Nikolaeva**, O. V. Savinova**, V. F. Eremin**, F. Z. Galin*, and G. A. Tolstikov*

*Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, Bashkortostan, 450054 Russia, **State Research Institute of Epidemiology and Microbiology, Minsk, Belarus

Abstract: Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex type 1 virus. The conjugate of betulonic acid 3-oxime with L-methionine is also active toward HIV-1. The tested compounds mainly show no activity toward the ECHO6 virus, which is devoid of a coat.

Key words: amides, antiviral activity, betulonic acid, lupane triterpenoids, peptides

Russian Journal of Bioorganic Chemistry, Vol. 30, No. 2, 2004, р . 148

Synthesis and Immunomodulating Activity of New Amino Acid Derivatives of Glycyrrhizic Acid and Its Methyl Ester

R. M. Kondratenko*, L. A. Baltina**, ¹ E. V. Vasil’eva**, Kh. M. Nasyrov*, ² R. M. Kireeva*, N. Zh. Baschenko*, S. M. Fridman*, L. A. Baltina (Jr.)*, and G. A. Tolstikov**

*Bashkortostan State Medical University, Ufa, Bashkortostan, 450074 Russia **Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, Bashkortostan, 450054 Russia

Abstract: New amino acid derivatives of glycyrrhizic acid and its methyl ester were selectively synthesized using active N-succinimide esters. The compounds with residues of glycine ethyl ester and alanine methyl and butyl esters increased the level of agglutinins and hemolysins in blood serum of mice two- to threefold in comparison with the control upon parenteral administration at a dose of 2 mg/kg for 14 days.

Key words: glycyrrhizic acid, amino acid derivatives, methyl ester; immunomodulating activity

Russian Journal of Bioorganic Chemistry, Vol. 30, No. 3, 2004, р . 275

The Synthesis and Antiviral Activity of Glycyrrhizic Acid Conjugates with - D -Glucosamine and Some Glycosylamines

R. M. Kondratenko*, L. A. Baltina*, ¹ S. R. Mustafina*, E. V. Vasil’eva*, R. Pompei**, D. Deidda**, O. A. Plyasunova***, A. G. Pokrovskii***, and G. A. Tolstikov*

*Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Russia, **Department of Medical Sciences, University of Cagliari, Italy, ***Vector State Scientific Center of Virusology and Biotechnology, pos. Koltsovo, Novosibirsk oblast, 633159 Russia

Abstract: Glycyrrhizic acid and its 30-methyl ester were conjugated with 2-amino-1,3,4,6-tetra-O-acetyl-2-deoxy--D-glucopyranose, 2,3,4,6-tetra-O-acetyl--D-glucopyranosyl amine, 2,3,4-tri-O-acetyl--L-arabinopyranosyl amine, 2-acetamido-2-deoxy--D-glucopyranosyl amine, and -D-galactopyranosyl amine using N,N'-dicyclohexylcarbodiimide and its mixtures with N-hydroxybenzotriazole. Structures of the conjugates were confirmed by IR, UV, ¹H, and ¹³C NMR spectroscopy. The glycoconjugate with the residues of 2-acetamido-2-deoxy--D-glucopyranosyl amine in the carbohydrate part of its molecule exhibited antiviral activity (ID₅₀ 4 g/ml) toward the herpes simplex type 1 virus (HSV-1) in the VERO cell culture. Two com-pounds demonstrated anti-HIV-1 activity (50–70% inhibition of p24) in a culture of MT-4 cells at concentrations of 0.5–20 g/ml.

Key words: antiviral activity, glycyrrhizic acid conjugates, D-glucosamine, -glycosylamines