The genus Euphorbia are well-known medicinal plants for many kinds of deseases with long history in China.[1a] Among the numerous kinds of species,Euphorbia peplus has been used in traditional medicine to treat asthma and psoriasis.[1b] The chemical constituents are normally diterpenoids,namely Euphorbia diterpenoids,which have been found to exhibit diverse significant bioactivities.In recent years,Qiu and Zhou reported the isolation and structure elucidation of five new diterpenoids named pepluacetal and pepluanols A-D(Figure 1).[2] Preliminary biological studies showed that they are inhibitors of Kv1.3,a validated target for the treatment of autoimmune diseases,with pepluanol B being the most effective with an IC50 value of 9.50 μM.In 2017,Ding and coworkers reported the total synthesis of(±)-pepluanol A(2)through a titanium(Ⅲ)-catalyzed reductive annulation strategy.[3] Our group has a long-time research focus on total synthesis of bioactive terpenoids.and recently we have accomplished the first total synthesis(±)-pepluanol B(3).Strategic transformations include sterically hindered Adol reaction,ring-closing metathesis.and substrate-controlled diastereoselective cyclopropanation to assemble the crucial tetracyclic scaffold.A bromo-epoxide is used as the mask of allylic alcohol to control the eight-membered ring conformation to install the desired atropselectivity and C13 chiral center.Enantioselective total synthesis of pepluanol B could also be achieved through the enzyme-catalyzed kinetic resolution of the bicyclic diol intermediate.