Biogenesis‐Guided Synthesis and Structural Revision of Sarocladione Enabled by Ruthenium‐Catalyzed Endoperoxide Fragmentation

Abstract

Sarocladione is the first 5,10:8,9-diseco-steroid with a 14-membered macrocyclic diketone framework to have been isolated from a natural source. Herein we report a biomimetic synthesis of sarocladione in only two or seven steps from inexpensive, commercially available ergosterol. The key feature of this synthesis was a novel ruthenium-catalyzed endoperoxide fragmentation, which transformed various saturated endoperoxides into olefinic diketones by cleavage of two C À C bonds. This synthesis allowed us to unambiguously determine the structure of sarocladione and provided experimental support for its revised biosynthetic origin. This work also vividly demonstrates that consideration of the biogenesis is a powerful tool for elucidating the structures of natural products.

Biogenesis‐Guided Synthesis and Structural Revision of Sarocladione Enabled by Ruthenium‐Catalyzed Endoperoxide Fragmentation

“…The spectroscopic data for our synthetic sarocladione were in good agreement with those reported by Gao [5] and Yang, [6] suggesting that our synthetic sample was identical to the natural product. Luckily, we were able to obtain an X-ray structure of the synthetic compound, [18] which clearly confirmed its structure to be 2, which has an embedded dihydrofuran-3-one moiety rather than a dihydropyran-4-one moiety. Furthermore, the stereocenters at C3 and C6 of 2 were unambiguously established to be in the S configuration.…”

Marine natural products

“…264 Biomimetic synthesis of sarocladione from ergosterol led to its structural revision from containing a dihydropyran-4-one moiety to a dihydrofuran-3-one moiety and also assignment of its absolute configuration as 808 . 265 Aperorydine G was isolated as a first time MNP and its absolute configuration determined as 809 , 266 and (12 S )-12-hydroxymonocerin 810 was also isolated as a new MNP. 267 Triquinane (−)-asperaculin A has been synthesised in a 13 step process employing biodivergent Baeyer–Villiger oxidation, 268 and steroid-sterigmatocystin heterodimer asperversin A has been prepared by an 11 step asymmetric method.…”

Structure and Biological Activity of Ergostane-Type Steroids from Fungi

“…A new steroid sarocladione ( 174 ) bearing a 5,10:8,9-diseco moiety was isolated from the deep-sea-derived fungus Sarocladium kiliense [ 292 ]. The initially proposed configuration at C-3 and C-7 proved to be incorrect and was revised to 3 S ,7 R through the chemical synthesis [ 293 ]. Cytotoxic studies of compound 174 revealed no apparent cellular toxicities.…”