Efficient access to isomeric 2,3-dihydroxy lupanes: first synthesis of alphitolic acid

Alphitolic acid (3) is a naturally occurring lupane type of pentacyclic triterpene, which possesses various pharmacological properties. Efficient synthesis of 3 has been accomplished in 10 steps with an overall yield of 19% starting from the readily available diketone 11. An alternative approach to the key intermediate 17 has also been developed, and based on this approach, 3 could be obtained in 10 steps with an overall yield of 26% starting from 11. Moreover, seven other isomeric 2,3-dihydroxy lupanes 4-10 have been synthesized. The synthesized triterpenes 3-10 were evaluated for their inhibitory activity against rabbit muscle GPa (RMGPa), and some of them exhibited moderate inhibitory activity against RMGPa.