Enantioselective total synthesis of briarellins E and F: the first total syntheses of briarellin diterpenes.
Enantioselective total syntheses of briarellin E (4) and briarellin F (5) have been achieved starting with (S)-(+)-carvone and (S)-(-)-glycidol. These total syntheses are the first of briarellin diterpenes. The central step in these syntheses is acid-promoted condensation of cyclohexadienyl diol 15 and (Z)-alpha,beta-unsaturated aldehyde 16 to form, with complete stereocontrol, the hexahydroisobenzofuran core and six stereocenters of these coral metabolites. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehyde 17 to remove the extraneous carbon introduced in the Prins-pinacol step, chemo- and stereoselective hydroxyl-directed epoxidation of dienyl alcohol 18 to incorporate the C3 oxygen stereocenter, regio- and stereoselective rearrangement of epoxy ester 19 to install the C4 oxygen substituent, efficient dehydrative cyclization of a 1,6-diol intermediate to form the oxepane ring, and diastereoselective Nozaki-Hiyama-Kishi cyclization of vinyl iodide aldehyde 25 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. These total syntheses establish the absolute configurations of 4 and 5, define a concise strategy for the total synthesis of briarellin diterpenes, and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for stereocontrolled synthesis of complex oxacyclic natural products.
Corminboeuf
Olivier
O
Department of Chemistry, 516 Rowland Hall, University of California-Irvine, Irvine, CA 92697-2025, USA.
Overman
Larry E
LE
Pennington
Lewis D
LD
D000818:Animals; D003063:Cnidaria / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis*; D004988:Ethers, Cyclic / Q000138:chemical synthesis*; D013237:Stereoisomerism
D004224:Diterpenes; D004988:Ethers, Cyclic; C475784:briarellin E; C475783:briarellin F