Total Synthesis of (±)-Cochlearol A

Abstract

Total synthesis of (±)-cochlearol A was accomplished, which features a cis 6/6 B/D ring synthesis. A TMSOTf-promoted lactonization of tert-butoxy ketoester produced the desired lactone with quaternary carbon. The cis configuration of the B/E ring is essential for regioselective B/D ring formation. Finally, simple deprotections and transformations gave cochlearol A in 16 steps from known ethyl 4-tert-butoxyacetoacetate.

Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity ofGanodermameroterpenoids

“…Given that the construction of the cis 6/6 ring is more difficult than trans isomers, Qin′s group designed a TMSOTf-promoted lactone cyclization which proceeded smoothly to give ketolactone 214 containing a quaternary carbon from ketoester 213 , which was originally formed by consecutive alkylation of ethyl 4- tert -butoxyacetoacetate ( 212 ) with aryl ethyl iodide and 4-bromo-1-butene. 100 With the strong Lewis acid TiCl 4 , the addition of arene to the ketone gave the desired tertiary alcohol 215 in 92% yield. Furthermore, a sequence of cyclization, aldehyde, reduction, oxidation, demethylation, and hydrogen reduction of 216 finally afforded cochlearol A ( 225 ) in 38% yield (Scheme 9).…”

“…Furthermore, a sequence of cyclization, aldehyde, reduction, oxidation, demethylation, and hydrogen reduction of 216 finally afforded cochlearol A ( 225 ) in 38% yield (Scheme 9). 100…”

Construction of the Hexacyclic Core of Dispirocochlearoids A—C via a Diels−Alder Reaction

“…[ 6 ] Therefore, several polycyclic Ganoderma meroterpenoids have been completely synthesized. [ 7 ]…”

Total Synthesis of Cochlearol B via a Catellani- and Visible Light-Enabled [2+2]-Cycloaddition Approach

“…The structure of cochlearol B (2) was originally deduced based on NMR and HRMS analysis and shown to feature a 4/5/6/6/6-fused polycyclic ring system with a central hepta-substituted cyclobutane core, which includes three stereogenic centers and three quaternary carbon atoms. Both cochlearol B (2) and ganocin B (3) contain a common chromane core, however ganocin B possesses a structurally distinct spiro [4,5]decane ring. 3 Notably, both cochlearol A (1) and cochlearol B (2) were isolated as racemates and were shown to exert renoprotective effects on renofibrosis by inhibiting upregulation of collagen I, fibronectin, and -SMA.…”