473-98-3

Usage

Uses

Used in Pharmaceutical Industry:
Betulin is used as an anti-cancer agent for its ability to induce apoptosis in various cancer cell lines, such as Jurkat cells, A549 lung carcinoma cells, and HeLa cervical carcinoma cells.
Used in Dermatological Applications:
Betulin is used as an anti-irritant and antiseptic in acne treatment, sunburn products, soothing lotions, and aftershaves due to its astringent properties and effectiveness in treating acne and eczema.
Used in Folkloric Medicine:
Betulin is used in traditional medicine for bathing skin eruptions, as it was considered beneficial for skin conditions.
Used in Chemical Industry:
Betulin is used in the preparation of betulinic acid, which has various applications, including anti-HIV, antimalarial, and anti-inflammatory activities.
Used in Atherosclerosis Treatment:
Betulin is used as a cholesterol-lowering agent, as it inhibits the SREBP-driven pathway of cholesterol and fatty acid biosynthesis, leading to decreased lipid levels and increased insulin sensitivity.
Used in Anticancer Applications:
Betulin is used as an antineoplastic agent, demonstrating anticancer effects by inducing apoptosis in various cancer cell lines.
Used in Antihyperlipidemia Applications:
Betulin is used as an antihyperlipidemic agent, helping to lower fasting blood glucose and insulin levels and reduce fat cell size in white adipose tissue in high-fat diet mice.

Extract

Betulin is an extract from bark of the white birch tree, which has been known since the 18th century and is chemically defined. Betulin was discovered by German-Russian chemist Johann Tobias Lowitz. He was the first scientist to study and characterise betulin, and in doing was one of the first to isolate an active plant ingredient. Betulin is a substance of pure plant origin that gives the birch bark its typical white colour. Betulin protects birch trees from environmental effects, such as extreme temperatures, pest infestations and solar radiation.

Physical and Chemical Properties

It is white crystalline powder, soluble in alcohol, chloroform and benzene, slightly soluble in cold water, petroleum ether.

Extraction method

Currently Betulin is obtained mainly through direct extraction, and mainly by solvent reflux extraction and recrystallization purification Specifically: 1. Extract betulin from ethanol solution. After heating reflux about 5h, the extract is vacuum distillated and recrystallized with ethanol for 2 to 3 times with ethanol to obtain crude product of betulin. 2. The crude product was recrystallized from methanol/chloroform (1: 1) (every 80g crude product requires 300mL methanol/chloroform solution).The mixture is allowed to stand overnight and then suction filtered to obtain white needle-like betulin. 3. Ultrasonic treatment for 20min when refluxing is carried out, and the extraction yield and product purity of betulin can be improved through the destruction of bark organization. 4. The optimum conditions of supercritical CO2 fluid extraction are as follows: the amount of modifier was 115mL/(g birch bark powder); extraction pressure is 20MPa; extraction temperature was 55 ℃; liquid CO2 flow rate was 10kg/h.

Identification method

HPLC conditions for betulin: Isolated Constituent: Betulin（10μl sample injection） Column Stationary Phase: C18(150×2)mm 5μ Column Mobile phase: Acetonitrile/water =30:70 Flow rate (ml/min)；0.2Detection Wavelength (nm)：270 Column Temperature：30℃

Physiological functions

Betulin and its derivatives as biological agents has shown great potential in the treatment of HIV and cancer by interfering with the post-life cycle of the virus, which is related to the entry as well as growth and maturing of virus. ?As an effective anti-tumor drug, it can directly cause certain types of tumor cells to start self-destruction of the apoptosis program, and can slow down the growth of several types of tumor cells. It can reduce dietary induced obesity, reduce lipid content in serum and tissue and improve insulin sensitivity. It has mild anti-inflammatory properties at higher concentrations, and its anti-inflammatory properties are largely due to inhibition of non-neural gene pathways. Betulin in the body can inhibit the maturation of sterol regulatory element binding protein (SBERPs), thereby reducing the biosynthesis of cholesterol and fatty acid. In addition, with its anti-inflammatory, anti-virus effect and functions of inhibiting protein dissolution in the hair fiber, improving the luster of damaged hair and promoting hair growth and other activities, it can be used in food, cosmetics and pharmaceutical industries.

Storage

Cool and dry, kept from light and temperature.

References

http://www.imlan.de/en/infothek/what-is-betulin.html

Anticancer Research

In addition, triterpenoids (betulin and its derivatives) isolated from HSSEactivated the signaling pathway regulated by p53 family genes, leading to the inhibition of BC cell viability or even the induction of apoptosis. And also, theseresearchers found that all the triterpenoids had no effect on normal breast cells.These findings provide an important basis for the use of those triterpenoids in thedevelopment of alternative therapies for breast cancer treatment (Hsu et al. 2015).

InChI:InChI=1/C30H50O2/c1-19(2)20-10-15-30(18-31)17-16-28(6)21(25(20)30)8-9-23-27(5)13-12-24(32)26(3,4)22(27)11-14-29(23,28)7/h20-25,31-32H,1,8-18H2,2-7H3/t20-,21+,22?,23?,24-,25?,27-,28+,29+,30+/m0/s1

Synthetic route

betulin diacetate (1721-69-3) → betulin (473-98-3)

Conditions	Yield
With potassium hydroxide In ethanol for 2h; Heating;	96%
With potassium hydroxide; ethanol In toluene for 2h; Heating / reflux;	93%
With sodium hydroxide In tetrahydrofuran; methanol at 20℃; for 168000h;

3,28-bis(O-THP)-betulin → betulin (473-98-3)

Conditions	Yield
With montmorillonite K-10 In methanol at 40 - 50℃; for 2h;	95%

betulin 3,28-bis-O-trifluoroacetate → betulin (473-98-3)

Conditions	Yield
With sodium hydroxide In ethanol; toluene at 60℃; for 3h;	94%

Betulinic acid (472-15-1) → betulin (473-98-3) + betulinic aldehyde (13159-28-9, 92594-07-5)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 4h; Heating;	A 90% B 5%

Betulinic acid (472-15-1) → betulin (473-98-3)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran for 5h; Reflux; Inert atmosphere; Sealed tube;	90%
Multi-step reaction with 2 steps 1: 1 g / diethyl ether; CH2Cl2 / 0 °C 2: 0.65 g / LiAlH4 / tetrahydrofuran / 3 h / Heating View Scheme
Multi-step reaction with 2 steps 2: LAH View Scheme

betulin diacetate (1721-69-3) → betulin (473-98-3) + betulin monoacetate (27570-20-3)

Conditions	Yield
With calcium hydroxide In methanol; chloroform for 24h; Ambient temperature;	A 10% B 89%
With magnesium methanolate In tetrahydrofuran; methanol for 72h; Ambient temperature;	A 14% B 81%
With sodium methylate In tetrahydrofuran; methanol for 48h; Ambient temperature;	A 53.1% B 43.4%

methyl betulinate (2259-06-5, 25493-95-2) → betulin (473-98-3)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 10 - 20℃;	76%
With lithium aluminium tetrahydride
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether for 3h; Heating;
With lithium aluminium tetrahydride In tetrahydrofuran for 3h; Heating;	0.65 g

betulinic aldehyde (13159-28-9, 92594-07-5) + acrylic acid methyl ester (292638-85-8) → (R)-4-[3β-hydroxy-28-norlup-20(29)-en-17β-yl]-γ-butyrolactone (1228273-12-8) + betulin (473-98-3)

Conditions	Yield
With samarium; 1,2-Diiodoethane; tert-butyl alcohol In tetrahydrofuran at 0℃; Inert atmosphere;	A 47% B n/a

betulonic aldehyde (4439-98-9) → betulin (473-98-3) + 3-epi-betulinic aldehyde

Conditions	Yield
With sodium hydroxide; dihydrogen peroxide; L-Selectride 1.) THF, -20 deg C, min, 2.) THF, 1 h; Yield given. Multistep reaction. Yields of byproduct given;

betulinic acid → betulin (473-98-3)

Conditions	Yield
With tetrahydrofuran; lithium aluminium tetrahydride; diethyl ether

methanol (67-56-1) + betulin 3-O-palmitate → hexadecanoic acid methyl ester (112-39-0) + betulin (473-98-3)

Conditions	Yield
With potassium hydroxide for 3h; Heating;

3β-O-cis-feruloylbetulin (1256450-16-4) → betulin (473-98-3)

Conditions	Yield
With potassium hydroxide In methanol at 65℃; for 10h;

28-acetoxybetulin (27686-35-7) + acrylonitrile (107-13-1) → 3-[3β-hydroxylup-20(29)-en-28-yloxy]propanenitrile (1239919-26-6) + betulin (473-98-3) + 3β-(2-cyanoethoxy)lup-20(29)-en-28-yl acetate (1309960-59-5) + 3β,28-di(2-cyanoethoxy)lup-20(29)-ene (1309960-47-1)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium hydroxide In 1,4-dioxane; water at 20℃; for 24h; Inert atmosphere;	A 5 %Chromat. B 22 %Chromat. C 64 %Chromat. D 9 %Chromat.

3-O-myristoylbetulin → betulin (473-98-3)

Conditions	Yield
With methanol; potassium hydroxide for 2h;

3β-O-cis-caffeoylbetulin → betulin (473-98-3)

Conditions	Yield
With potassium hydroxide at 20℃; for 12h;

betulin (473-98-3) → lupane-3β,28-diol (55029-05-5, 7372-31-8)

Conditions	Yield
With hydrogen; 10percent Pd/C In tetrahydrofuran; methanol under 2068.65 Torr;	100%
With hydrogen; palladium 10% on activated carbon In methanol; dichloromethane under 1810.07 Torr; for 16h;	100%
With hydrogen; platinum(IV) oxide In methanol; chloroform for 8h;	99%

betulin (473-98-3) + acetic anhydride (108-24-7) → betulin diacetate (1721-69-3)

Conditions	Yield
With pyridine; dmap at 20℃; for 1h;	100%
With dmap In tetrahydrofuran at 20℃;	100%
montmorillonite acid clay for 0.0333333h; microwave irradiation;	99%

betulin (473-98-3) → allobetulin (1617-72-7, 5713-24-6, 125225-35-6, 137173-47-8)

Conditions	Yield
Montmorillonite KSF In dichloromethane for 3.5h; Heating;	99%
With trifluoroacetic acid In chloroform at 22℃; for 0.133333h;	97%
With amberlyst 15 In chloroform Reflux;	96%

betulin (473-98-3) → 19β,28-epoxy-A-neo-18α-olean-3(5)-ene (6714-21-2)

Conditions	Yield
With bithmuth(III) triflate hydrate In dichloromethane for 40h; Reflux;	98%
With kieselguhr; xylene
Multi-step reaction with 2 steps 1: 99 percent / montmorillonite KSF / CH2Cl2 / 3.5 h / Heating 2: 65 percent / montmorillonite K10 / cyclohexane / 2.5 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 68 percent / PCl5 / petroleum ether / 1.) 0 deg C, 30 min, 2.) r.t., 45 min 2: 61 percent / montmorillonite K10 / CH2Cl2 / 40 °C View Scheme

betulin (473-98-3) + trityl chloride (76-83-5) → (3β)-28-(triphenylmethoxy)lup-20(29)-en-3-ol (431879-42-4)

Conditions	Yield
With dmap In N,N-dimethyl-formamide at 60℃;	98%
With pyridine; dmap at 80℃;	85%
With pyridine; dmap In N,N-dimethyl-formamide Reflux; regioselective reaction;	76%

betulin (473-98-3) + 2,4,6,8-tetraacetyl-2,4,6,8-tetraazabicyclo<3,3,0>octan-3,7-dione (10543-60-9) → betulin diacetate (1721-69-3)

Conditions	Yield
With trifluoroacetic acid In chloroform at 70℃; for 1h;	98%

betulin (473-98-3) → betulonic aldehyde (4439-98-9) + betulinic aldehyde (13159-28-9, 92594-07-5)

Conditions	Yield
With [bis(acetoxy)iodo]benzene; 1,5-dimethyl-9-azanoradamantane N-oxyl In dichloromethane at 25℃; for 0.75h; Reagent/catalyst; Inert atmosphere;	A 51% B 97%
With pyridinium chlorochromate In dichloromethane at 20℃; for 1.5h;	A 82% B 17%
With 1‐methyl‐2‐azaadamantane‐N‐oxyl; [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 2h; Catalytic behavior; Reagent/catalyst;	A 51% B 49%

betulin (473-98-3) → betulinic aldehyde (13159-28-9, 92594-07-5)

Conditions	Yield
With N-chloro-succinimide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrabutyl-ammonium chloride; sodium hydrogencarbonate; potassium carbonate In tetrahydrofuran; water at 20℃;	97%
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; sodium chlorite; tetrabutylammomium bromide; sodium hypochlorite In phosphate buffer; dichloromethane at 35℃;	92%
With 2,2,6,6-tetramethyl-piperidine-N-oxyl; tetrabutylammomium bromide; sodium hypochlorite In phosphate buffer; dichloromethane at 30℃; pH=6.8;	87%

chloro-trimethyl-silane (75-77-4) + betulin (473-98-3) → O,O'-bis-(trimethylsilyl)-betulin (212708-99-1)

Conditions	Yield
With pyridine at 0 - 20℃; for 3h;	97%
With 1H-imidazole In dichloromethane at 25℃; for 3h;
With 1H-imidazole In dichloromethane at 0℃;

maleic anhydride (108-31-6) + betulin (473-98-3) → (2Z,2′Z)-4,4′-[lup-20(29)-en-3β,28-diyl]bis(oxy)bis(4-oxobut-2-enoic acid)

Conditions	Yield
With N,N-dimethyl-aniline In benzene for 50h; Reflux;	97%

phthalic anhydride (85-44-9) + betulin (473-98-3) → betulin 3,28-bishemiphthalate (2519-35-9)

Conditions	Yield
With pyridine for 15h; Addition; Heating;	96%
With pyridine; dmap for 30h; Heating;	76%
Stage #1: phthalic anhydride; betulin With pyridine; dmap for 37h; Heating / reflux; Stage #2: With hydrogenchloride In water; ethyl acetate	76%
With dmap for 24h;

betulin (473-98-3) → 19β,28-epoxy-A-neo-5β-methyl-25-nor-18α-olean-9(10)-ene

Conditions	Yield
With bithmuth(III) triflate hydrate In dichloromethane for 8h; Reflux;	96%

3,4-dihydro-2H-pyran (110-87-2) + betulin (473-98-3) → 3-hydroxy-28-[(tetrahydro-2H-pyran-2-yl)oxy]lup-20(29)-ene (189571-52-6)

Conditions	Yield
With pyridinium p-toluenesulfonate In dichloromethane for 72h; Ambient temperature;	95%
With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 20h;	80%
With pyridinium p-toluenesulfonate In dichloromethane at 20℃; for 72h; Inert atmosphere;	57%

bromobutyric acid (2623-87-2) + betulin (473-98-3) → 3β-hydroxylup-20(29)-en-28-yl 4-bromobutanoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Steglich Esterification;	95%
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;	80%

betulin (473-98-3) + acetylene (74-86-2) → C32H52O2

Conditions	Yield
With potassium hydroxide In dimethyl sulfoxide at 80℃; for 2.5h;	95%

nicotinic acid (59-67-6) + betulin (473-98-3) → 3β,28-di-O-nicotinoyl-lupa-20(29)-ene (473806-27-8)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 24h; regioselective reaction;	95%

3-ethyl-3-methylglutaric anhydride (6970-57-6) + betulin (473-98-3) → 3-Ethyl-3-methyl-pentanedioic acid mono-[(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-(3-carboxymethyl-3-methyl-pentanoyloxy)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-3a-ylmethyl] ester

Conditions	Yield
With dmap In pyridine at 95℃;	94%
With pyridine; dmap at 95℃;

betulin (473-98-3) → betulin diphosphate

Conditions	Yield
Stage #1: betulin With pyridine; trichlorophosphate In 1,4-dioxane at 10 - 20℃; for 24h; Stage #2: With water In 1,4-dioxane	94%
With pyridine; trichlorophosphate In acetone at 0℃; for 1h;	69%

betulin (473-98-3) → 30-iodolup-20(29)-ene-3β,28-diol (1429785-14-7)

Conditions	Yield
With iodine In N,N-dimethyl acetamide at 25℃; for 0.0166667h; Kinetics; Thermodynamic data; Concentration; Temperature; Solvent;	94%

betulin (473-98-3) + pyridine-3-carbonyl chloride hydrochloride (20260-53-1) → betulin dinicotinate

Conditions	Yield
With pyridine; tributyl-amine at 0 - 20℃; for 4h;	93.6%

betulin (473-98-3) → betulonic aldehyde (4439-98-9)

Conditions	Yield
With oxalyl dichloride; dimethyl sulfoxide In dichloromethane at -30℃; Svern oxidation;	93%
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -15 - 20℃; Swern oxidation;	93%
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane Swern oxidation;	90%

betulin (473-98-3) + Cyclohexanecarboxylic acid (98-89-5) → Cyclohexanecarboxylic acid (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-3a-ylmethyl ester + Cyclohexanecarboxylic acid (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-hydroxymethyl-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-9-yl ester + C44H70O4

Conditions	Yield
tetrachlorobis(tetrahydrofuran)hafnium(IV) In chlorobenzene for 16h; Heating;	A 93% B n/a C 7%

betulin (473-98-3) + 2-Methylpropionic anhydride (97-72-3) → C38H62O4

Conditions	Yield
With dmap for 1h;	93%
With dmap In dichloromethane for 1h;	93%

pyridine-4-carboxylic acid (55-22-1) + betulin (473-98-3) → betulin 3β,28-di-O-isonicotinate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 22℃; for 24h; regioselective reaction;	93%

succinic acid anhydride (108-30-5) + betulin (473-98-3) → 3,28-dihydroxylupan bis(hydrogen succinate)

Conditions	Yield
With pyridine for 15h; Addition; Heating;	92%
With pyridine for 8h; Reflux;	92%
Stage #1: succinic acid anhydride; betulin With pyridine; dmap for 12h; Heating / reflux; Stage #2: With hydrogenchloride In water; ethyl acetate	67%

betulin (473-98-3) + 1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) → O,O'-bis-(trimethylsilyl)-betulin (212708-99-1)

Conditions	Yield
With phosphomolybdic acid In chloroform for 0.833333h; Heating;	92%

Upstream product

• 472-15-1 Betulinic acid 
• 2259-06-5 methyl betulinate 
• 1721-69-3 betulin diacetate 
• 4439-98-9 betulonic aldehyde 
• 67-56-1 methanol 
• 13159-28-9 betulinic aldehyde 
• 292638-85-8 acrylic acid methyl ester 
• 1256450-16-4 3β-O-cis-feruloylbetulin 
• 27686-35-7 28-acetoxybetulin 
• 107-13-1 acrylonitrile 
• 137553-04-9 C₆₆H₉₆O₂₉S 

Downstream Products

• 87001-74-9 Toluene-4-sulfonic acid (1R,3aS,5aR,5bR,9S,11aR)-9-hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysen-3a-ylmethyl ester 
• 2519-35-9 3,28-bis-(2-carboxy-benzoyloxy)-lup-20⁽²⁹⁾-ene 
• 486-34-0 1,2,7-trimethylnaphthalene 
• 55029-05-5 lupane-3β,28-diol 
• 4439-98-9 betulonic aldehyde 
• 5354-50-7 3,28-bis-benzoyloxy-lup-20⁽²⁹⁾-ene 
• 6060-06-6 platanic acid 
• 139254-38-9 3β-Hydroxy-30-norlupane-20,28-dione 
• 1617-72-7 allobetulin 
• 1721-69-3 betulin diacetate 
• 27686-35-7 28-acetoxybetulin 
• 4481-62-3 betulonic acid 
• 27570-20-3 betulin monoacetate 
• 13159-28-9 betulinic aldehyde 

Relevant academic research and scientific papers

Betulin 3,28-Bis-O-trifluoroacetate: Synthesis and molecular structure

The reaction of betulin with excess trifluoroacetic anhydride gave the corresponding 3,28-bis-O-trifluoroacetate whose molecular structure as a slightly bent "stairway" was determined by X-ray analysis.

Three new lupane-type triterpenes from Ceriops tagal

Three new lupane-type triterpenes, 3α-O-trans-feruloylbetulinic acid (1), 3α-O-trans-coumaroylbetulinic acid (2) and 3β-O-cis- feruloylbetulin (3), together with 10 known triterpenes (4-13), were isolated from the aerial parts of the mangrove plant Ceriop

Anti-tumor betulinic acid derivative and preparation method thereof

The invention discloses an anti-tumor betulinic acid derivative and a preparation method thereof. The preparation method comprises the following steps: by taking betulinic acid as a raw material, carrying out carboxyl reduction, generating sulfonate by hydroxyl and sulfonyl chloride, eluting and purifying by a silica gel column and the like to obtain the betulinic acid derivative with a novel structure. Pathological experiments show that the compound has a remarkable in-vitro proliferation inhibition effect on human ovarian cancer cells (A2780), human lung cancer cells (A-549) and human cervical cancer cells (Hela), and can be used as a pilot compound for development of antitumor drugs. The method for preparing the betulinic acid derivative provided by the invention has the characteristics of simple preparation process, low cost and suitability for industrial mass production.

Cytotoxic and NF-κB and mitochondrial transmembrane potential inhibitory pentacyclic triterpenoids from Syzygium corticosum and their semi-synthetic derivatives

Syzygium is a large genus of flowering plants, with several species, including the clove tree, used as important resources in the food and pharmaceutical industries. In our continuing search for anticancer agents from higher plants, a chloroform extract of the leaves and twigs of Syzygium corticosum collected in Vietnam was found to be active toward the HT-29 human colon cancer cell line. Separation of this extract guided by HT-29 cells and nuclear factor-kappa B (NF-κB) inhibition yielded 19 known natural products, including seven triterpenoids, three ellagic acid derivatives, two methylated flavonoids, a cyclohexanone, four megastigmanes, a small lactone, and an aromatic aldehyde. The full stereochemistry of (+)-fouquierol (2) was defined for the first time. Biological investigations showed that (+)-ursolic acid (1) is the major cytotoxic component of S. corticosum, which exhibited also potent activities in the NF-κB and mitochondrial transmembrane potential (MTP) inhibition assays conducted, with IC50 values of 31 nM and 3.5 μM, respectively. Several analogues of (+)-ursolic acid (1) were synthesized, and a preliminary structure-activity relationship (SAR) study indicated that the C-3 hydroxy and C-28 carboxylic acid groups and 19,20-dimethyl substitution are all essential in the mediation of the bioactivities observed for this triterpenoid.

Bioactive Triterpenoids from the Twigs of Chaenomeles sinensis

Chaenomeles sinensis has been consumed traditionally for the treatment of throat diseases, diarrhea, inflammatory diseases, and dry beriberi. Repeated chromatography of the CHCl3-soluble fraction from the 80% MeOH extract of C. sinensis twigs led to the isolation of three new triterpenoids, sinenic acid A (1), 3β-O-cis-feruloyl-2α,19α-dihydroxyurs-12-en-28-oic acid (2), and 3β-O-cis-caffeoylbetulin (3), together with 20 analogues. The chemical structures of 1-3 were determined using diverse NMR techniques and HRMS data analysis, chemical methods, and computational approaches supported by advanced statistics (CP3). All the purified compounds were evaluated not only for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) but for their potential neuroprotective effects through induction of nerve growth factor in C6 glioma cells. Their anti-inflammatory effects were also assessed by measuring nitric oxide levels in lipopolysaccharide-insulted murine microglia BV2 cells.

Synthesis of bioactive 28-hydroxy-3-oxolup-20(29)-en-30-al with antileukemic activity

An easy and efficient route to partial synthesis of bioactive 28-hydroxy-3-oxolup-20(29)-en-30-al (1), starting from betulinic acid (2), has been developed (eight steps, 44% overall yield). Structures of all the compounds were determined by spectral studies (IR, 1H, 13C NMR, MS, NOESY, COSY, etc.). Compound 1 and the precursors (2, 3, 5, and 7) showed antiproliferative activities against human K562 leukemia, murine WEHI3 leukemia, and murine MEL erythroid progenitor.

Structure and bioassay of triterpenoids and steroids isolated from sinocalamus affinis

Five triterpenoids with a new 25-norfern carbon skeleton (1-5), a lupane triterpenoid (6), and four 20-hydroxyprogesterone acyl esters (7-10), together with 23 known compounds, were isolated from the stem (with skin removed) of Sinocalamus af f inis. The absolute configuration of compound 1 was confirmed by single-crystal X-ray crystallographic analysis using anomalous scattering of Cu Kα radiation. Compounds 1-5 exhibited inhibitory activity against protein tyrosine phosphatase 1B.

METHOD AND APPARATUS FOR SIMULTANEOUSLY MANUFACTURING ULTRA PURE BETULIN AND HIGHLY PURE BETULINIC ACID FROM BIRCH BARK

The present invention provides a method of simultaneously producing ultrapure betulin and highly-pure betulinic acid a from bark of a birch tree, which is configured such that a crude extract including 70 ～ 83% of betulin, 4 ～ 8% of betulinic acid and polar pigment components are prepared from the bark (mainly outer bark) of a birch tree naturally growing in the northern hemisphere of 34° north latitude, such as Korea, China, Europe and the like, using a polar organic solvent, and highly-pure betulin included in this crude extract is crystallized using a mixed polar organic solvent to obtain a crystallized product, and then ultrapure betulin, having purity of 99.5% or more and highly-pure betulinic acid having purity of 95% or more are simultaneously produced from the crystallized product including highly-pure betulin as a major component.

Synthetic transformations of higher terpenoids: XXIV.* synthesis of cyanoethyl derivatives of lupane triterpenoids and their transformation into 1,2,4-oxadiazoles

Cyanoethylation of lupane triterpenoids was performed. Amide oximes of 3β-O-(2-cyanoethyl)- betulinic acid methyl ester and 3β-O-acetyl-28-O- (2-cyanoethyl)betulin and the corresponding O-[2-(1,2,4-oxadiazol- 3-yl)ethyl] lupane derivatives were obtained. Pleiades Publishing, Ltd., 2011.

Synthesis and biological evaluation of antitumor-active γ-butyrolactone substituted betulin derivatives

The plant triterpenes betulin and betulinic acid (BA) are triterpenes featuring interesting pharmacological properties. Starting from substituted betulinic aldehydes, we used them as lead structures for the synthesis of several γ-butyrolactones and butenolides. Their antitumor activity was examined for 15 cancer cell lines using a SRB-assay and their apoptotic action was documented by trypan-blue test and DNA laddering. Several compounds revealed a higher activity than betulinic acid.