Glycyrrhizic Acid (GL) is the major bioactive
triterpene glycoside of licorice root (Glycyrrhiza Radix) extracts possessing a wide range of pharmacological properties (anti-inflammatory, anti-
ulcer,
anti-allergic, anti-dote,
anti-oxidant, anti-
tumor, anti-viral etc.). Official sources of GL are Glycyrrhiza glabra L. and Gl. uralensis Fish. (Leguminosae). The content of GL in licorice root is 2-24% of the dry weight. GL is one of the leading natural compounds for clinical trials of chronic active viral
hepatitis and
HIV infections (preparation
Stronger Neo-Minophagen C, SNMC), and its monoammonium
salt (
glycyram, tussilinar) is used as an anti-inflammatory and
anti-allergic remedy. The synthetic transformations of GL on carboxyl and
hydroxyl groups were carried out to produce new bioactive derivatives for medicine. GL
esters were produced containing fragments of bioactive
acids (4-nitrobenzoic, cinnamic, salycilic, acetylsalycilic, nicotinic, isonicotinic). Bioactive
amides of GL were synthesized using chloroanhydride technique and N,N'-diciclohexylcarbodiimide (DCC) method. The synthesis of acylthioureids and
semicarbazones was carried out via the reaction of triacylisothiocianate of
penta-O-acetyl-GL with primary
amines and
hydrazines. The chain of transformations of trichloranhydride of
penta-O-acetyl-GL was made with the introduction of diazoketone groups in the molecule. A new group of GL derivatives to be
triterpene glycopeptides was prepared by the activated
esters method (N-hydrohysuccinimide-DCC or N-hydroxybenzotriazol-DCC) using alkyl (methyl, ethyl, propyl, butyl, tert-butyl) or benzyl (4-nitrobenzyl)
esters of
amino acids. The glycyrrhizyl analogs of the known immunostimulator, N-acetyl-muramoyldipeptide (MDP), were synthesized using
Reagent Woodward K. A series of ureids and
carbamates of GL was synthesized containing 5-amino-5-desoxy-D-xylopyranose units. The synthesis of 4-nitro-4-desoxy-glycosides, modified analogs of GL, was carried out by the oxidative splitting of the
carbohydrate part of GL with NaIO(4).
Triterpene 2-desoxy-D-glycosides, analogs of GL, were prepared by the glycal method in the presence of
iodine-containing promoters or
sulfonic acid cation-exchange resin KU-2-8 (H+) and LiBr. New anti-inflammatory and
anti-ulcer agents were found among GL derivatives such as
esters,
amides, ureids,
carbamates, thioureids and
glycopeptides. GL
glycopeptides are of interest as
immunomodulators. Some of the chemically modified GL derivatives (
salts,
amides,
glycopeptides) were potent HIV-1 and HIV-2 inhibitors in vitro. Preparation
niglizin (
penta-O-
nicotinate of GL) was studied clinically as an
anti-inflammatory agent and is of interest for studies as hepatoprotector and HIV inhibitor.