Betulin

Birken-holz, n. birch wood, -holzteer, m. birch-(wood) tar. -holzteerseifc, /, birch tar soap, -kampher, m, birch camphor, betulin. -kohle, /, birch charcoal, -rinde, /, birch bark. -liftdaiUil, -61, n. oil of betula, cdl of sweet bircb. -teer, m. tdrch tar. -teerdt, n. birch tar oil. 

Figure 3 Triterpene derivative betulinic acid RPR103611 N - N-[3p-hydroxyl-up-20(29-ene-28-oyl]-8-aminooctanoyl -L-statine. 

The clinical potential of the fusion inhibitors in the therapy and/or prophylaxis of HIV infections remains a subject for further study. Since these compounds directly interfere with syncytium formation, they should be able to block HIV infections generated by both free virus particles and HIV-infected cells. It is not known how readily the virus may become resistant to this class of compounds. For betulinic acid, it has been ascertained that some HIV-1 strains (e.g., NDK) may be resistant ab initio. 

The plant is known to produce norbisabolane diterpenes, including phyllanthusols A and B, which are both cytotoxic (36). From the bark, pentacyclic triterpenoids, phyl-lanthol, and olean-12en-3[3-ol (p-amyrin) have been isolated (37). Note lupane- and oleanane-type triterpenoids isolated from the bark of Phyllanthus flexuosus, such as olean-12-en-3 (3,15 a-diol, olean-12-en-3 [3,15 a,24-triol, lupeol, and betulin inhibited the enzymatic activity of topoisomerase II activity with IC50 values in the range of 10 to 39 p.M (38). 

Betulin and lupeol, together with low amounts of lupenone, betulone and betulinic acid, are characteristic of birch bark [87,153 157]. All these compounds are pentacyclic triterpenoids with a lupane skeleton. In addition to triterpenoids, birch bark contains high amounts of a lipid material, called suberin [158]. 

M.M. O Connell, M.D. Bentley, C.S. Campbell, B.J.W. Cole, Betulin and lupeol in bark from four white barked birches, Phytochemistry, 27, 2175 2176 (1988). 

The general pattern of the mass spectrum and the presence of peaks at mlz 424, 426 and 442, attributed, respectively, to the molecular ions of lupeol, lupenone and betulin, suggest the presence of birch bark tar. This study provided the first evidence that birch bark tar was used for assembling bronze tools during the Iron Age in Europe. 

Regert et al. studied [9] a series of 30 Neolithic hafting adhesives from lake dwellings at Chalain (France) using an analytical procedure based on GC/MS analysis involving solvent extraction (dichloromethane) and trimethylsilylation. In the majority of the samples a series of triterpenoid compounds with a lupane structure was clearly identified on the basis of their TMS mass spectra. In particular, the presence of betulin, betulone, lupenone, lupeol and lupa-2,20(29)-dien-28-ol allowed birch bark tar to be identified. In other samples the co-occurrence of other plant biomarkers such as a-amyrin,(3-amyrin... 

Mass spectra of betulin, betulone, lupenone, lupeol, lupa-2,20(29)-dien-28-ol and lupa-2,20(29)-diene are reported in Figure 8.8. The mass spectra are obtained using El at 70 eV and an ion trap as analyser. 

Figure 8.8 Mass spectra of (a) betulin (TMS derivative), (b) lupeol (TMS derivative), (c) lupa 2,20(29) dien 28 ol (TMS derivative), (d) betulone (TMS derivative), (e) lupenone and (f) lupa 2,20(29) diene...

Betts electrolytic process, 4 5 Betulin, 24 556-557 Betulinic acid, 24 556-557 Beulah-Zap coal, empirical composition, 6 730t... 

Figure 7.2 Partial capillary gas chromatogram displaying the principal lipid solvent soluble constituents of a black tarry deposit on the surface of a Neolithic potsherd from Ergolding Fischergasse, Bavaria, Germany. The sample was trimethylsilylated prior to GC (for further details see Heron et al., 1997). Peak identities (confirmed by GC-MS analysis) 1, lupenone 2, lupeol 3, betulin 4, betulinic acid.

Fujioka T, Kashiwada Y, Kilkuskie RE, Cosentino EM, Balias LM, Jiang JB, Janzen WP, Chen IS, Lee K-H. (1994) Anti-AIDS agents, 11. betulinic acid and platanic acid as anti-HIV principles from syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids. J Nat Prod 57 243-247. 

Ganguly A, Das B, Roy A, Sen N, Dasgupta SB, Mukhopadhayay S, Majumder HK. (2007) Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death. Cancer Res 67 11848-11858. 

Kashiwada Y, Hashimoto E, Cosentino LM, Chen C-H, Garrett PE, Lee K-H. (1996) Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents. J Med Chem 39 1016-1017. 

Sami A, Taru M, Sahne K, Jari Y-K. (2006) Pharmacological properties of the ubiquitous natural product betulin. Eur J Pharm Sci 29 1-13. 

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