Synthesis of betulin derivatives and their protective effects against the cytotoxicity of cadmium

Hiroya, Kou; Takahashi, Taisuke; Miura, Nobuhiko; Naganuma, Akira; Sakamoto, Takao

doi:10.1016/s0968-0896(02)00172-4

Cited by 40 publications

(23 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The structure could be further refined as 3-OAc by the downfield shift of H-3 to δ H 4.42 (1H,dd,J = 11.2,4.8 Hz) relative to that of 3. Compound 4 was therefore identified as 3-acetoxybetulinic aldehyde (Hiroya et al, 2002). To the best of our knowledge, the current study is the first report on the isolation of compounds …”

Section: Resultsmentioning

confidence: 79%

An anti-influenza component of the bark of Alnus japonica

et al. 2010

View full text Add to dashboard Cite

This study to identify anti-influenza components of the bark of Alnus japonica resulted in the isolation of four lupane-type triterpenes (1-4) and one steroid (5). Their structures were characterized on the basis of physicochemical properties, NMR evidence, and ESI-MS data compared with reported data in the literature. Betulinic aldehyde (3) exhibited a particularly strong anti-influenza effect against KBNP-0028 relative to a positive control.

show abstract

Section: Resultsmentioning

confidence: 79%

An anti-influenza component of the bark of Alnus japonica

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Fraction 3 was column-chromatographed over silica gel 60 with n-hexane-acetone (80 : 20) as eluent to give 3ˇ-friedelinol 14 (15 mg) and 3ˇ-acetoxy-28-hydroxyurs-12-ene 15 (8 mg). Fraction 4 was subjected to repetitive column chromatography over silica gel 60 and HPLC separation over normal phase column to give 3ˇ-acetoxyurs-12-en-28-al 15 (12 mg), 3ˇ-hydroxyurs-20(29)-en-28-al 16 (8 mg),ˇ-sitosterol (25 mg), ursolic acid (40 mg), coumarin 17 (8 mg), 3ˇ-acetoxy betulin 18 (10 mg), 5,6˛-epoxy-5˛-stigmastan-3ˇ-ol (6 mg) (1) and 5,6ˇ-epoxy-5ˇ-stigmastan-3ˇ-ol (10 mg) (2). Fraction 5 gave˛-amyrin (10 mg) and adian-5-en-3ˇ-ol 19 (20 mg) on column chromatography and HPLC treatment using gradient of n-hexane-ethyl acetate.…”

Section: Extraction and Isolationmentioning

confidence: 99%

Two isomeric epoxysitosterols from Rhododendron formosanum: ¹H and ¹³C NMR chemical shift assignments

Krishna

Chang

Chou

2006

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

show abstract

“…Recently, Naganuma and his colleagues found that three natural triterpenes, betulin (1), uvaol (2), and soyasapogenol B (3), have reducing effects against the toxicity of cadmium chloride in HepG2 cells (Fig. 1).…”

mentioning

confidence: 99%

“…The results showed that both the polar functional group, found at either the C3 or C28 positions, and the isopropenyl group play important roles in reducing cadmium toxicity and the cytotoxicity of betulin (1). 2) However, it is difficult to carry out further investigation into the bioactivities of betulin because the only functional groups of this compound are hydroxyl and isopropenyl, both of which are crucial for its activity. Therefore, we decided to synthesize analogues of betulin, which could not be otherwise derived from natural products.…”

mentioning

confidence: 99%

The New Method for Introduction of an Allyl Group into the Angular Position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and Its Application to Chiral Wieland-Miescher Type Compound Synthesis

Hiroya

Takahashi

Shimomae

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Triterpenoid compounds are of interest because they occur widely in nature and have unique biological activities. Recently, Naganuma and his colleagues found that three natural triterpenes, betulin (1), uvaol (2), and soyasapogenol B (3), have reducing effects against the toxicity of cadmium chloride in HepG2 cells (Fig. 1). 1) They also reported that betulin induced certain proteins, though not metallothionein, which is the representative protein in reducing heavy metal toxicity. 1)To clarify the reduction mechanism of cadmium toxicity, we investigated the relationship between expression of activities and structures, with particular focus on the functional groups of betulin, using its analogues. The results showed that both the polar functional group, found at either the C3 or C28 positions, and the isopropenyl group play important roles in reducing cadmium toxicity and the cytotoxicity of betulin (1).2) However, it is difficult to carry out further investigation into the bioactivities of betulin because the only functional groups of this compound are hydroxyl and isopropenyl, both of which are crucial for its activity. Therefore, we decided to synthesize analogues of betulin, which could not be otherwise derived from natural products. Our synthetic strategy is summarized in Fig. 2, which shows the pentacyclic ring system being divided into two fragments: the AB fragment 4 and the DE fragment 5. Since our focus was on the angular substituents between the D and E rings, the starting material for 5 needed to be the optically pure bicyclo[4.4.0]decaline derivative 6b, and the starting material for 4 the Wieland-Miescher ketone 6a.The optically active Wieland-Miescher type bicyclic ketone 6a was effectively synthesized from the prochiral tricarbonyl compound 7a, using chiral proline as a chiral catalyst (Fig. 3).3-6) The optically pure 6a can be obtained by a single recrystallization, and can be utilized for subsequent syntheses of many natural products.7-11) However, the cyclization reaction of compounds with side chains other than a methyl group (e.g., allyl group 7b) was observed to have serious depreciation of the optical yield.12) In addition, proline did not work as a catalyst for this reaction, meaning a stoichiometric amount of proline is required to complete the reaction. If expensive synthetic proline has to be used, this presents a serious economic obstacle. Therefore, before starting the synthesis of the betulin analogues, it was decided to develop an efficient method for synthesizing optically pure bicyclo[4.4.0]decaline derivatives. Results and DiscussionThe essential features of the synthesis reaction are illustrated in Figs. 4 and 5. When the optically active diketone 8 was treated under acidic conditions, a mixture of the two diastereomers 9a and 9b resulted. However, by using an acidcatalyzed dehydration reaction, the mixture of 9a and 9b was converted to the single enantiomer 10. Using a dissolvingmetal reduction reaction with 10, it was expected that 11a The stereoselective introduction of an al...

show abstract

Synthesis of betulin derivatives and their protective effects against the cytotoxicity of cadmium

Cited by 40 publications

References 9 publications

An anti-influenza component of the bark of Alnus japonica

An anti-influenza component of the bark of Alnus japonica

Two isomeric epoxysitosterols from Rhododendron formosanum: ¹H and ¹³C NMR chemical shift assignments

The New Method for Introduction of an Allyl Group into the Angular Position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and Its Application to Chiral Wieland-Miescher Type Compound Synthesis

Contact Info

Product

Resources

About

Synthesis of betulin derivatives and their protective effects against the cytotoxicity of cadmium

Cited by 40 publications

References 9 publications

An anti-influenza component of the bark of Alnus japonica

An anti-influenza component of the bark of Alnus japonica

Two isomeric epoxysitosterols from Rhododendron formosanum: 1H and 13C NMR chemical shift assignments

The New Method for Introduction of an Allyl Group into the Angular Position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and Its Application to Chiral Wieland-Miescher Type Compound Synthesis

Contact Info

Product

Resources

About

Two isomeric epoxysitosterols from Rhododendron formosanum: ¹H and ¹³C NMR chemical shift assignments