Enantioselective Total Syntheses of (+)-Hippolachnin A, (+)-Gracilioether A, (-)-Gracilioether E, and (-)-Gracilioether F

: Li QG, Zhao K, Peuronen A, Rissanen K, Enders D, Tang YF

Publisher: AMER CHEMICAL SOC

: 2018

: Journal of the American Chemical Society

: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

: J AM CHEM SOC

: 140

: 5

: 1937

: 1944

: 8

: 0002-7863

DOI: https://doi.org/10.1021/jacs.7b12903

The Plakortin polyketides represent a structurally and biologically fascinating class of marine natural products. Herein, we report a unified strategy that enables the divergent syntheses of various Plakortin polyketides with high step-economy and overall efficiency. As proof-of-concept cases, the enantioselective total syntheses of (+)-hippolachnin A, (+)-gracilioether A, (-)-gracilioether E, and (-)-gracilioether F have been accomplished based on a series of bioinspired, rationally designed, or serendipitously discovered transformations, which include (1) an organocatalytic asymmetric 1,4 conjugate additidn to assemble the common chiral gamma-butenolide intermediate enroute to all of the aforementioned targets, (2) a challenging biomimetic [2+2] photocycloaddition to forge the oxacyclobutapentalene core of (+)-hippolachnin A, (3) a [2+2] photocycloaddition followed by one-pot oxidative cleavage of methyl ether/Baeyer-Villiger rearrangement to access (-)-gracilioether F, and (4) an unprecedented hydrogen-atom-transfer-triggered oxygenation of vinylcyclobutane to afford (+)-gracilioether A and (-)-gracilioether E in one pot.