“…The absence of a synthesis can, in part, be attributed to the incompatibility of biologically inspired polyene cyclization strategies for the assembly of the celastroids or, for that matter, any members of the friedelin-type of triterpenes. These reactions are highly desirable as they provide rapid access to relatively large molecules with multiple stereogenic centers in a single transformation from linear, polyunsaturated precursors. , Unfortunately, however, the biological polyene cyclization leading to celastrol is exceedingly difficult to reproduce in the laboratory due to a set of complex and energetically unfavorable methyl and hydride shifts. − The closest natural products to celastrol to be synthesized were the pentacyclic triterpenes, alnusenone, and friedelin, both of which were prepared by Ireland. − Attempts to implement polyene cyclizations for these natural products failed to improve access to the natural products, however, were inspirational for our studies. , …”