Today’s synthesis is a semisynthesis of (+)-Chromazonarol and (+)-Yuhazunone. These preps start a natural sesquiterpene fragrance Sclareolide. I haven’t developed the intuition yet, but clever functional group interconversion and novel synthetic techniques are the drivers behind remarkable semisyntheses.

Baran showcases the prep of a “Borono-Sclareolide” to access a wide range of Meroterpenoids.  A scalable semisynthesis from (+)-Sclareol to get to (+)-8-O-Acetylchromazonarol and (+)-8-O-Acetylyahazunone. A Li, Csuk, and Li collaboration cut’s Baran’s 7 step prep down to 5 (6 if you count) the Acetyl deprotection. Li, Csuk, and Li improve on Baran’s work by having the core finished in 3 steps compared to Baran’s 6 steps. In addition, Li, Csuk, and Li’s synthesis doesn’t hinge on a Alcohol directed hydroboration to set a stereocenter which resolves one of Baran’s issues. Wu also resolves this issue through a palladium cross coupling but given this groups goals of creating a divergent synthesis, they could not afford to save steps by sacrificing the functionality of the 1,4 benzoquinone.

Originally published: September 18, 2018