Simple synthesis of allobetulin, 28-oxyallobetulin and related biomarkers from betulin and betulinic acid catalysed by solid acids

Allobetulin (3a) and allobetulin acetate (3b) were efficiently prepared in excellent yield from betulin (2a) and betulin 3-acetate (2b) catalysed by a number of solid acids in refluxing dichloromethane. Sulfuric acid on silica, montmorillonite clays (both K10 and KSF), kaolinite, bleaching clay and toluene-p-sulfonic acid on silica are efficient catalysts for these conversions. Similarly, 28-oxyallobetulin (3c) and 28-oxyallobetulin acetate (3d) were obtained in good and excellent yield from betulinic acid (2c) and betulinic acid acetate (2d) respectively catalysed by montmorillonite K10. Two allobetulin related biomarkers, 19 beta,28-epoxy-A-neo-18 alpha-olean-3(5)-ene (4a) and A-neo-18 alpha-olean-3(5)-en-28-->19 beta-olide (4b) were synthesised either from 3a and 3c or directly from 2a and 2c in refluxing benzene or cyclohexane catalysed by montmorillonite K10. Two other biomarkers, 19 beta,28-epoxy-18 alpha-olean-2-ene (10a) and 18 alpha-olean-2-en-28-->19 beta-olide (10b) were also synthesised based on the above transformations. The direct formation of allobetulane related biomarkers from natural betulin 2a and betulinic acid 2c catalysed by clay mineral (montmorillonite) is of great geochemical interest.