Betulonic acid

Bioorg Med Chem. 2014 Jul 1;22(13):3292-300.

Synthesis of triterpenoid triazine derivatives from allobetulone and betulonic acid with biological activities.[Pubmed: 24844757]

The synthetic transformation and modification of natural products with the aim to improve the biological properties is an area of current interest. The triterpenoids betulin and betulinic acid are very abundant in nature and now are commercially available.
METHODS AND RESULTS:
In our study, starting from betulin and betulinic acid, we obtained allobetulone and Betulonic acid in a few synthetic steps. The ketone function at the A-ring was used as the starting point for the synthesis of a series of 1,2,4-triazine-fused triterpenoids. The alkylation and Liebeskind-Srogl coupling were used for further substitution of 1,2,4-triazines, and the intramolecular hetero Diels-Alder reaction leads to interesting fused thienopyridine derivatives. All new compounds were tested for their cytostatic activities against murine leukemia L1210, human cervix carcinoma HeLa and human lymphoblast CEM tumor cells.
CONCLUSIONS:
The results show that some triterpenoid triazine Betulonic acid derivatives have a promising cytostatic activity in vitro and could be used as potential leads for the development of new type of anti-cancer agents. Several compounds were also endowed with anti-HCMV activity in the low micromolar range.

Fitoterapia. 2003 Jul;74(5):489-92.

Antiviral activity of betulin, betulinic and betulonic acids against some enveloped and non-enveloped viruses.[Pubmed: 12837369]

METHODS AND RESULTS:
Antiviral properties of betulin, betulinic and Betulonic acids were investigated in cell cultures infected with herpes simplex type I, influenza FPV/Rostock and ECHO 6 viruses.
CONCLUSIONS:
All studied triterpenes were active against herpes simplex virus. Betulin and especially betulinic acid also suppressed ECHO 6 virus reproduction.

Eur J Med Chem . 2015;96:58-65.

Synthesis and biological evaluation of betulonic acid derivatives as antitumor agents[Pubmed: 25874331]

Abstract Structural modification was performed at the C-28 position of Betulonic acid (BetA). Twenty-five BetA derivatives were synthesized, and evaluated for their antitumor activities against MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines by MTT assay. Among the derivatives, most of the derivatives had significant antiproliferative ability (IC50 < 19 μM). Compound 3k, the most active compound, showed IC50 values of 3.6, 5.6, 4.2, 7.8, and 5.2 μM on the five cancer cell lines respectively, and was selected to investigate cell apoptosis by subsequent florescence staining and flow cytometry analysis. The results revealed that compound 3k could induce apoptosis in MGC-803 cell lines, and the apoptosis ratios reached 28.33% after 36 h of treatment at 10 μM. In addition, the study of cancer cell apoptotic signaling pathway indicated that the apoptosis of MGC-803 cells induced by compound 3k could be through the mitochondrial intrinsic pathway. Keywords: Antitumor; Apoptosis; Betulonic acid derivatives; Mitochondrial pathway; Synthesis.

Bioorg Med Chem. 2009 Jul 15;17(14):5164-9.

Efficient synthesis of the first betulonic acid-acetylene hybrids and their hepatoprotective and anti-inflammatory activity.[Pubmed: 19524443 ]

The Sonogashira reaction can be applied for the preparation of acetylenic derivatives of Betulonic acid where the triterpenoid moiety can serve as either the halo- or the acetylenic component. This reaction opened access to the first derivatives of Betulonic acid containing either the arylethynyl (C[triple bond]C-Ar(Het) or the ethynyl (C[triple bond]CH) moieties. From the fundamental perspective, this work illustrates the possibility of selective Pd-catalyzed cross-coupling at terminal acetylenes in the presence of a terminal alkene.
METHODS AND RESULTS:
Hepatoprotective and anti-inflammatory properties of selected acetylenic derivatives of Betulonic acid were investigated using the CCl4-induced hepatitis and carrageenan-induced edema models, respectively.

Phytochemistry. 2007 Mar;68(6):834-9.

Biotransformation of betulinic and betulonic acids by fungi.[Pubmed: 17258248]

Betulinic acid (1), a triterpenoid found in many plant species, has attracted attention due to its important pharmacological properties, such as anti-cancer and anti-HIV activities. The closely related, Betulonic acid (2) also has similar properties. In order to obtain derivatives potentially useful for detailed pharmacological studies, both compounds were submitted to incubations with selected microorganisms.
METHODS AND RESULTS:
In this work, both were individually metabolized by the fungi Arthrobotrys, Chaetophoma and Dematium, isolated from the bark of Platanus orientalis as well as with Colletotrichum, obtained from corn leaves; such fungal transformations are quite rare in the scientific literature. Biotransformations with Arthrobotrys converted Betulonic acid (2) into 3-oxo-7beta-hydroxylup-20(29)-en-28-oic acid (3), 3-oxo-7beta,15alpha-dihydroxylup-20(29)-en-28-oic acid (4) and 3-oxo-7beta,30-dihydroxylup-20(29)-en-28-oic acid (5); Colletotrichum converted betulinic acid (1) into 3-oxo-15alpha-hydroxylup-20(29)-en-28-oic (6) acid whereas Betulonic acid (2) was converted into the same product and 3-oxo-7beta,15alpha-dihydroxylup-20(29)-en-28-oic acid (4); Chaetophoma converted Betulonic acid (2) into 3-oxo-25-hydroxylup-20(29)-en-28-oic acid (7) and both Chaetophoma and Dematium converted betulinic acid (1) into Betulonic acid (2).
CONCLUSIONS:
Those fungi, therefore, are useful for mild, selective oxidations of lupane substrates at positions C-3, C-7, C-15, C-25 and C-30.