The chemical transformations of betulin

Betulin (1) is a naturally occurring pentacyclic lupane-type triterpenoid, isolated from the outer white birch bark. Betulin and its derivatives such as betulinic acid (2) and betulonic acid (3) are studied for their antitumor, antiviral, anti-inflammatory, hepatoprotective, antiparasitic, antibacterial and antimycotic activities [1,2,3]. Betulin is stable in a natural environment and examples of its microbial transformations are rare. The chemical transformations look to be the best way leading to structural analogs of betulin or its derivatives. We are interested in oxoanalogs of betulin. At first, we have studied the oxidation of betulin with common reagents. The reaction of betulin with Jones reagent afforded the mixture of ketoaldehyde (4), (53%) and betulonic acid (23%). We have also studied the oxidation of betulin and betulonic acid with 1.1 mol of m-chloroperbenzoic acid (m-CPBA). The reaction of betulin gave the epoxy betulin (5). Betulonic acid in the same conditions afforded also product of epoxydation of double bond. When the oxidation was carried out with 2.2 mol of m-CPBA, the mixture of epoxy betulonic acid (6) and epoxy lactone (7) was obtained. R1 R2 1 α-H, β-OH CH 2 OH 2 α-H, β-OH COOH 3 O COOH 4 O CHO 5 α-H, β-OH CH 2 OH 6 O COOH References: [1] Dzubak, P. et al. (2006) Nat. Prod. Rep. 23, 394–411. [2] Eiznhamer, D. et al. (2004) IDrugs 7,4, 359–373. [3] Kim, D.S.H.L. et al. (1998) Bioorg. Med. Chem. Lett. 8, 1707–1712.