28282-22-6

Usage

Uses

Used in Pharmaceutical and Medicinal Chemistry Research:
(1S,6aR,6bR,8aR,12R,12bR,14aR,14bR)-2,2,6a,6b,9,9,12-heptamethylicosahydro-10H-1,4a-(epoxymethano)picen-10-one is utilized as a compound of interest in pharmaceutical and medicinal chemistry research for its potential range of biological activities and unique structural features. Its high degree of stereochemical complexity and the presence of an epoxide functionality may contribute to its effectiveness in various therapeutic applications.

Upstream product

• 7020-34-0 betulone 
• 473-98-3 betulin 
• 1617-72-7 C₃₀H₅₀O₂ 
• 1617-72-7 C₃₀H₅₀O₂ 
• 106174-05-4 3β-acetoxy-19β,28-epoxy-18α-oleanan-2-one 
• 106144-68-7 19β,28-epoxy-2α-hydroxy-18α-oleanan-3-one 
• 74892-21-0 19β,28-epoxy-18α-olean-1-en-3-one 
• 106174-06-5 (18α,19β) 19,28-epoxy-2-hydroxy-olean-1-en-3-one 
• 3419-10-1 2,2-dibromoallobetulon 
• 1617-72-7 allobetulin 
• 17307-63-0 19β,28-Epoxy-18α-oleanan-2-one 
• 113306-81-3 19β,28-epoxy-3-ethoxy-18α-olean-2-ene 
• 113306-80-2 19β,28-epoxy-3-methoxy-18α-olean-2-ene 
• 137127-99-2 19β,28-epoxy-18α-oleanan-3β-yl nitrite 

Downstream Products

• 107280-34-2 taraxastadiene-(2.20)-diyl-(3.28)-dibenzoate 
• 1379668-47-9 C₃₇H₅₂N₂O 

Relevant academic research and scientific papers

Synthesis and characterization of some new 1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.

Antiproliferative effect of mitochondria-targeting allobetulin 1,2,3-triazolium salt derivatives and their mechanism of inducing apoptosis of cancer cells

Herein we report the targeting effect of 1,2,3-triazolium salt derivatives of allobetulin on cancer cells mitochondria and their antiproliferative mechanism. A series of allobetulin derivatives with 1,2,3-triazolium positively charged units was designed and synthesized by multi-component triazolization reaction and alkylation. The screening of cytotoxicity showed that all the 1,2,3-triazolium salt derivatives of allobetulin displayed better cytotoxicity than the parent compound allobetulin and commercial anticancer drugs gefitinib. The most potent compound 4q showed strong anticancer activity, especially for Eca-109 cells. Compound 4n showed the strongest inhibitory effect on SGC-7901 cells. Further anticancer mechanism studies indicated that compounds 4n and 4q induced apoptosis through the mitochondrial pathway. Compounds 4n and 4q acted on mitochondria to cause an increase in intracellular reactive oxygen species and a change in the level of apoptosis-related protein (Bcl-2, Bcl-xL and Bax), which resulted in a decrease in membrane potential and activation of caspase family to induce cancer cells apoptosis. Meanwhile, compounds 4n and 4q could induce cancer cells apoptosis by arresting the cell cycle. Due to the strong cytotoxicity of compounds 4n and 4q, they are expected to become new anticancer agents and deserve further study.

Synthesis of 1,2-azole derivatives on the basis of α,β-unsaturated triterpene aldehydes

[Figure not available: see fulltext.] α,β-Unsaturated lupane and 19β,28-epoxy-18α-oleanane aldehydes were used in the synthesis of triterpenoids bearing substituted 1,2-azole moieties (1-acetyl-3-methyl-4,5-dihydro-1H-pyrazole and 3-methyl-4,5-dihydroisoxazole) at the rings А and Е. The route of synthesis for these 1,2-azole derivatives of triterpenes included an aldol condensation of α,β-unsaturated aldehydes with acetone, the products of which (α,β-unsaturated methyl ketone and β-hydroxy ketone) underwent a further cycloaddition reaction with acetylhydrazide and hydroxylamine. Cytotoxic activity studies of the synthesized compounds against seven cancer cell lines (Hep-2, HCT116, MS, RD TE32, A549, MCF-7, and PC-3) showed that the highest cytotoxicity (IC50 0.66–11.97 μM) against all tested cell lines was exihbited by 19β,28-epoxy-18α-oleanane aldehyde and the products of its condensation reactions with acetone and acetylhydrazide.

Synthesis and cytotoxic activity of triterpenoid thiazoles derived from allobetulin, methyl betulonate, methyl oleanonate, and oleanonic acid

A total of 41 new triterpenoids were prepared from allobetulone, methyl betulonate, methyl oleanonate, and oleanonic acid to study their influence on cancer cells. Each 3-oxotriterpene was brominated at C2 and substituted with thiocyanate; subsequent cyclization with the appropriate ammonium salts gave N-substituted thiazoles. All compounds were tested for their in vitro cytotoxic activity on eight cancer cell lines and two non-cancer fibroblasts. 2-Bromoallobetulone (2b) methyl 2-bromobetulonate (3b), 2-bromooleanonic acid (5b), and 2- thiocyanooleanonic acid (5c) were best, with IC50 values less than 10 mm against CCRF-CEM cells (e.g., 3b: IC50=2.9 μm) as well as 2'-(diethylamino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5 f, IC50=9.7 μm) and 2'-(N-methylpiperazino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5k, IC50=11.4 μm). Compound 5c leads to the accumulation of cells in the G2 phase of the cell cycle and inhibits RNA and DNA synthesis significantly at 1xIC50. The G2/M cell-cycle arrest probably corresponds to the inhibition of DNA/RNA synthesis, similar to the mechanism of action of actinomycin D. Compound 5c is new, active, and nontoxic; it is therefore the most promising compound in this series for future drug development. Methyl 2-bromobetulonate (3b) and methyl 2-thiocyanometulonate (3c) were found to inhibit nucleic acid synthesis only at 5xIC50. We assume that in 3b and 3c (unlike in 5c), DNA/RNA inhibition is a nonspecific event, and an unknown primary cytotoxic target is activated at 1xIC50 or lower concentration.

Lupane and 18α-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Lupane derivatives containing an electronegative substituent in the position 2 of the skeleton are often cytotoxic, however, the most active compounds are not selective enough. To further study the influence of a substituent in the position 2 in lupane and 18α-oleanane derivatives on their biological properties, we prepared a set of 38 triterpenoid compounds, 19 of them new, most of them substituted in the position 2. From betulin, we obtained 2-bromo dihydrobetulonic acid and 2-bromo allobetulon and their substitutions yielded derivatives with various substituents in the position 2 such as amines, amides, thiols, and thioethers. Nitration of allobetulon and dihydrobetulonic acid gave 2-nitro and 2,2-dinitro derivatives. Fifteen derivatives had IC50 50 4.6 μM and caused significant block of the tumor cells in S and slightly in G2/M transition and caused strong inhibition of DNA and RNA synthesis at 5 × IC50. 2-Amino allobetulin is the most active derivative of 18α-oleanane skeletal type prepared in our research group to date.

Allobetulin derived seco-oleananedicarboxylates act as inhibitors of acetylcholinesterase

Ring opening of allobetulone gave either seco-acid 8 or di-acid 4. These acids were converted into esters that were screened by Ellman's assay. A dibutenylester of low cytotoxicity (NIH 3T3 murine embryonic fibroblasts) was shown to be a good mixed-type inhibitor (Ki = 3.39, Ki′ = 2.26 μM) for acetylcholinesterase.

Simple structural modifications confer cytotoxicity to allobetulin

Abstract A variety of allobetulin derivatives was synthesized from allobetulin or allobetulone. These compounds were screened for their cytotoxic activity using a photometric SRB assay employing six different human tumor cell lines. In summary, opening of

Heterocycle-fused lupane triterpenoids inhibit Leishmania donovani amastigotes

The synthesis of heterocyclic betulin derivatives and their activity against Leishmania donovani is reported. Betulonic acid was used as a versatile intermediate. Several different fused heterocycles were introduced at the 2,3-position of the lupane skeleton including isoxazole, pyrazine, pyridine, indole and pyrazole rings. Also the 28-position was modified. Three compounds, 5, 8 and 25, showed low micromolar activity with IC50 values of 13.2, 4.3 and 7.2 μM, respectively. Compound 8 showed the best activity and selectivity, and its activity was tested on infected macrophages using a concentration, 5 μM, where no macrophage toxicity was exhibited. Interestingly, the activity of compound 8 on axenic amastigotes and Leishmania-infected macrophages was similar.

Antineoplastic agents. 595. structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer1

The lupane-type triterpene betulin (1) has been subjected to a series of structural modifications for the purpose of evaluating resultant cancer cell growth inhibitory activity. The reaction sequence 7 11 12 was especially noteworthy in providing a betulin-derived amine dimer. Other unexpected synthetic results included the 11 and 13/1417 conversions, which yielded an imidazo derivative. X-ray crystal structures of dimer 12 and intermediate 25 are reported. All of the betulin modifications were examined for anticancer activity against the P388 murine and human cell lines. Significant cancer cell growth inhibition was found for 4, 8, 9, 15/16, 19, 20, 24, and 26, which further defines the utility of the betulin scaffold.

Cytotoxic heterocyclic triterpenoids derived from betulin and betulinic acid

The aim of this work was to synthesize a set of heterocyclic derivatives of lupane, lup-20(29)-ene, and 18α-oleanane, and to investigate their cytotoxic activities. Some of those heterocycles were previously known in the oleanane (allobetulin) group; however, to our knowledge the syntheses and biological activities of lupane heterocycles have not been reported before. Starting from betulin (1) and betulinic acid (2), we prepared 3-oxo compounds and 2-bromo-3-oxo compounds 3-10, 2-hydroxymethylene-3-oxo compounds 11-13 and β-oxo esters 14-16. Condensation of these intermediates with hydrazine, phenylhydrazine, hydroxylamine, or thiourea yielded the pyrazole and phenylpyrazole derivatives 17-22, pyrazolones 23-25, isoxazoles 26 and 27, and thiazoles 28-31. Fifteen compounds (14-16, 18-25, and 29-32) have not been reported before. The cytotoxicity was measured using panel of seven cancer cell lines with/without MDR phenotype and non tumor MRC-5 and BJ fibroblasts. The preferential cytotoxicity to cancer cell lines, particularly to hematological tumors was observed, the bromo acids 5, 6 showed highest activity and selectivity against tumor cells.