Expedient Synthesis Of Alphitolic Acid And Its Naturally Occurring 2-O-Ester Derivatives

The expedient synthesis of alphitolic acid (1) as well as its natural C-3-epimer and 2-O-ester derivatives was accomplished in a few steps from the readily commercially available betulin (9). A Rubottom oxidation delivered an alpha-hydroxy group in a stereo-and chemoselective manner. The diastereoselective reduction of the a-hydroxy ketone was key to accessing the 1,2-diol moiety of this class of natural products. Our concise and stereoselective synthetic protocol allowed the gram-scale synthesis of these natural products, which will facilitate future biological evaluations.