Total Synthesis of (±)-Phaeocaulisin A

Keywords

(±)-phaeocaulisin A - guaianolide sesquiterpene - Kulinkovich reaction - ring-opening carbonylation - aldol reaction - Tamao–Fleming oxidation

Significance

Dai and co-workers report the total synthesis of (±)-phaeocaulisin A. The catalytic cyclopropanol ring-opening carbonylation protocol was investigated and displayed as a general method to access various γ-keto esters. Choice of base was crucial for desired chemoselective aldol cyclization to later construct the oxaspirolactone of the tetracyclic skeleton of the natural product.

Comment

Retrosynthetically devised in a concise manner, sequential Kulinkovich cyclopropanation and palladium-catalyzed cyclopropanol ring-opening carbonylation from diene D gave keto ester G. Subsequent ozonolysis yielded dione H followed by aldol cyclization to access cycloheptanone I. Ketalization, lactonization and oxidation yielded tetracycle K. Installation of the α-methylene group followed by alkene migration finally gave (±)-phaeocaulisin A.

Publication History

Article published online:
28 January 2025