Total Synthesis of Illisimonin A and Merrilactone A

Abstract

Illicium sesquiterpenes are a large family of biologically active secondary metabolites isolated from Illicium species of plants and are well-known for their activity of neurite outgrowth in cultured neurons. Herein, we propose a comprehensive biosynthetic pathway for illicium sesquiterpenes and report a synthetic route to illisimonin A and merrilactone A based on it. We think that the carbon scaffolds of most of the illicium sesquiterpenes could be synthesized from a dicarbonyl derivative of allo-cedrane through retro-Dieckmann condensation, oxidative cleavage and aldol reaction at suitable oxidation states in Nature. The common intermediate for illisimonin A and merrilactone A similar to the dicarbonyl derivative of allo-cedrane was assembled with up to 82 % ee by an asymmetric intramolecular desymmetrizing reductive Heck reaction by the use of a new type of chiral phosphine ligand. The syntheses of illisimonin A and merrilactone A supported the key transformations of the proposed biosynthetic pathway.

Divergent Total Syntheses of Illicium Sesquiterpenes through Late-Stage Skeletal Reorganization

“…Driven by a long desire to decipher the chemical relationship across the different subfamilies of Illicium sesquiterpenes, we envisaged that the door from the allo -cedrane family to the anislactone family could probably be opened through a biomimetic oxidative skeletal rearrangement cascade consisting of oxidative cleavage the C10–C11 bond, hemiketalization of C7-ketone with C4 hydroxyl group, subsequent retro-Dieckmann condensation to break the C6–C7 bond, and final intramolecular aldol reaction to form a five-membered ring (see arrows around intermediate 24 , Scheme B) . After a brief screening, we identified PCC as the oxidant to cleave the C10–C11 bond.…”

A novel approach to the tetracyclic frameworks of anislactone-type sesquiterpenoids

“…Consequently, a myriad of innovative strategies have been devised, resulting in the successful development of more than ten synthetic routes. 1–12 Undoubtedly, the central focus of these investigations has been on the synthesis of the crucial 5/5 framework encompassing the B–C rings. Notably, radical cyclization 3,6,7 a ,8,9,10 a ,11 has been predominantly employed for forming the octahydropentalene ring system.…”

“…Additionally, methodologies such as RCM, 5 intramolecular aldol reaction 4 and borylative cyclization of enynes 10 a have proven to be effective for forging the fused B–C rings. More recently, bio-inspired strategies based on the intramolecular aldol reaction and a biomimetic oxidation-initiated skeletal rearrangement cascade have been elegantly developed by Yang 12 and Zhang, 10 b respectively.…”

“…However, extensive manipulations were necessary to reassemble the A-ring or C-ring. Alternatively, stereoselective establishment of CQCCs could be attained through stepwise strategies, which relied on key reactions such as methylation, 6,11 aldol condensation, 8,10 b ,12 or radical cyclization 9,10 a to introduce the C6-stereocenter. It is evident that this approach would lengthen the overall synthetic process since the C5-stereocenter needed to be preinstalled.…”

Total Synthesis of (±)-Rubriflordilactone A

“…To our delight, exposure of 15 to a combination of BF 3 ·OEt 2 (100 equiv), 4 Å MS, and 2-methyl-2-butene (20 equiv) in refluxing dichloroethane furnished 16a and 16b in 58% combined yield ( dr = 2.3:1). Subsequently, treatment of 16a with MOMCl followed by Mukaiyama hydration, via the reaction conditions developed by Studer and co-workers, delivered pentacyclic indanone 6 in 53% yield over two steps. At this point, the left part of 3 had been accomplished.…”