Synthesis of the 8,19‐Epoxysteroid Eurysterol A

Abstract

We report the first chemical synthesis of eurysterol A, a cytotoxic and antifungal marine steroidal sulfate with a unique C8−C19 oxy‐bridged cholestane skeleton. After C19 hydroxylation of cholesteryl acetate, used as an inexpensive commercial starting material, the challenging oxidative functionalization of ring B was achieved by two different routes to set up a 5α‐hydroxy‐7‐en‐6‐one moiety. As a key step, an intramolecular oxa‐Michael addition was exploited to close the oxy‐bridge (8β,19‐epoxy unit). DFT calculations show this reversible transformation being exergonic by about −30 kJ mol−1. Along the optimized (scalable) synthetic sequence, the target natural product was obtained in only 11 steps in 5 % overall yield. In addition, an access to (isomeric) 7β,19‐epoxy steroids with a previously unknown pentacyclic ring system was discovered.

Marine natural products

“…500 A number of terpenoids and steroids were also synthesised for the rst time in 2020. [501][502][503][504][505] In what may be a world rst, three Australian groups have independently reported the reassignment of the same class of sponge metabolite; all three publications were received at the respective journal editorial offices within four months of each other in late 2019, and all were published in January or early February of 2020. Reinspection of the NMR data of echinosulfone A suggested the originally published structure may be incorrect.…”