Betulone

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]. 

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...

The structure of benulin (134), a lupene hemiacetal from Bursera arida, has been confirmed by X-ray analysis. An investigation of several Senecio species has resulted in the isolation of a series of lupane derivatives which include the acids (135), (137), and (139), the corresponding aldehydes (136), (138), and (140), the ketone (141), and betulonic acid. Three more triterpenoids (142)—(144) have... 

Betulin (lup-20(29)-ene-3,28-diol) is an abundant naturally occurring triterpene, and it is found predominantly in bushes and trees forming the principal extractive (up to 30% of dry weight) of the bark of birch trees. Betulin and its derivatives such as betulinic acid have many interesting pharmacological properties, such as cytotoxic activity against many tumour cell lines and anti-HIV activity with a new mechanism of action. Several synthetic betulin derivatives that have been chemically modified at the positions C-3 and C-28 of the lupane skeleton were produced, and the anti-leishmanial inhibition activity of compounds was evaluated at 50 pM against Leishmania donovani and Leishmania tropica. Betulonic acid had the best anti-leishmanial activity with... 

Several studies have been devoted to the one-step oxidative conversion of betu-lin to betulinic acid with selected strains of fxmgal microorganisms [29-31], as well to the microbial conversion of betulin or betulinic acid to their 3-oxo coxmterparts (betu-lone or betulonic acid, respectively) [27,32-34]. 

Incubation of betulinic acid (1) and 23-hydroxybetulinic acid (19) (Figure 28.6) with Nocardia sp. NRRL 5646 afforded their corresponding methyl esters, betulinic acid methyl ester (20), and 23-hydroxybetulinic acid methyl ester (21), respectively [42]. FTowever, microbial transformation of betulonic acid (7) by the same Nocardia sp. NRRL 5646 at a preparative scale [43] resulted in addition in the isolation of an imex-pected a-hydroxylation product, methyl 2a-acetoxy-3-oxo-lup-20(29)-en-28-oate (22) (6.5% yield), beside the expected compoxmd methyl 3-oxo-lup-20(29)-en-28-oate (23) (50% yield). The structures of metabolites were elucidated unambiguously by ESI-MS and 2D NMR spectroscopy. 

Microbial transformations of betulinic acid (6) and betulonic acid (7) by endophytic fungi [39, 40]. 

In summary, microbial hydroxylation of betulin, lupeol, and betulinic-betulonic acids was thus useful to produce hydroxylated lupane derivatives at C-7p, C-15a, C-ip, but also frequently in other positions C-11, C-12, C-6, C-2a, C-30, C-25 (in order of priority, see Figure 28.7), with sometimes several combinations of hydroxylated sites. A summary of these results with yields is presented in Table 28.1. Besides the existing chemical methods, a variety of metabolites with potential new or increased biological activities may be obtained. Some of them have been more recently isolated in plants as natural products. 

Betulonic acid (7) C. longirostre IPO 9873 ]40] 3,4-scco-4-Hydroxy-lup>-20(29)-ene-3,28-dioicacid 4... 

L.-W. Qian, J. Zhang, J.-H. Liu, B.-Y. Yu, Direct microbial-catalyzed asymmetric a-hydrox-ylation of betulonic acid by Nocardia sp. NRRL 5646, Tetrahedron Lett. 2009. 50,2193-2195. 

In accord with an a f/-parallel relationship between the migrating carbon (C20) and the entering nucleophile, the carbon chlorine bond in 364-Cl is found to be in the equatorial (a) configuration. On the other hand, the acid-catalyzed cyclization of methyl betulonate (367), and related diol occurs so as to form an axial carbon-oxygen bond to C19, despite the ostensibly unfavorable stereoelectronics 453, 454). It is possible, however, that this transformation is more complex than a simple ring expansion followed by lactonization. 

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