Unified synthesis of quinone sesquiterpenes based on a radical decarboxylation and quinone addition reaction.
A unified synthesis of several quinone sesquiterpenes is described herein. Essential to this strategy is a novel radical addition reaction that permits the attachment of a fully substituted bicyclic core 16 to a variably substituted quinone 10. The addition product 15 can be further functionalized, giving access to natural products with a high degree of oxygenation at the quinone unit. The quinone addition reaction is characterized by excellent chemoselectivity, taking place only at conjugated and unsubstituted double bonds, and regioselectivity, being strongly influenced by the resonance effect of heteroatoms located on the quinone ring. These features were successfully applied to the synthesis of avarol (1), avarone (2), methoxyavarones (4, 5), ilimaquinone (6), and smenospongidine (7), thereby demonstating the synthetic value of this new method.
Ling
Taotao
T
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA.
Poupon
Erwan
E
Rueden
Erik J
EJ
Kim
Sun H
SH
Theodorakis
Emmanuel A
EA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D053138:Cyclohexenes; D011809:Quinones / Q000138:chemical synthesis*; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013379:Substrate Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D053138:Cyclohexenes; D011809:Quinones; D012717:Sesquiterpenes; C046374:avarone; C467077:ilimaquinone; C023663:avarol