A Double Allylation Strategy for Gram‐Scale Guaianolide Production: Total Synthesis of (+)‐Mikanokryptin. Issue 6 (3rd January 2017)

• Record Type: Journal Article
• Authors: Hu, Xirui; Xu, Silong; Maimone, Thomas J.
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 6(2017)
• Page Start: 1624
• Page End: 1628
• Publication Date: 2017-01-03
• Subjects: allylation -- guaianolides -- natural products -- terpenes -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201611078
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: With over 5000 members isolated to date, sesquiterpene lactones represent a prolific source of medicinal agents with several derivatives in human clinical trials. The guaianolides, a major subset of this group, have been intensely investigated from both medicinal and chemical‐synthesis perspectives for decades. To date, the myriad stereochemical permutations presented by this enormous family have precluded the synthesis of many unique members. Herein we report the total synthesis of the trans ‐fused 8, 12‐guaianolide (+)‐mikanokryptin in 10 steps from (+)‐carvone. Notably, this synthesis is the first gram‐scale total synthesis of a guaianolide natural product. Abstract : Can't have too much of a good thing : The myriad stereochemical permutations of the guaianolide sesquiterpene lactones have precluded the synthesis of many unique members. Now a total synthesis of the trans ‐fused 8, 12‐guaianolide (+)‐mikanokryptin (see scheme) in 10 steps from (+)‐carvone has been developed on the basis of two highly robust and scalable allylation processes, which were critical for processing large quantities of material.