A Dehydrogenative Diels–Alder/Aromatization Sequence to Access 6/6/6/6/5 Pentacyclic Steroids: Their Anti-inflammatory Activities

6/6/6/6/5 Pentacyclic steroids represent an emerging class of architecturally unique and biologically promising steroids. Herein, we developed a DDQ-mediated dehydrogenative Diels–Alder/aromatization cascade reaction between ergosterol derivatives and dienophiles inspired by plausible biosynthetic pathways, which enabled straightforward access to various 6/6/6/6/5 pentacyclic steroids in 24–66% yields. This work offers significant advantages in assembling 6/6/6/6/5 pentacyclic steroids such as the use of inexpensive starting materials, mild reaction conditions, and simple operations. Furthermore, the anti-inflammatory investigations of these steroids on LPS-stimulated RAW264.7 cells led to the discovery of four steroids (i.e., 2h, 4f, 5b, and 5f) as potent anti-inflammatory agents with minimal side effects. This work not only achieves a rapid and biomimetic approach to the unique pentacyclic steroids but also unveils their therapeutic potential in anti-inflammation therapy.