Synthesis of (±)‐Merrilactone A by a Desymmetrization Strategy

Abstract

A concise synthesis of (±)-merrilactone A has been accomplished featuring desymmetrization of a C -symmetric dilactone, Rh -catalyzed intramolecular hydroacylation of a 4-alkynal, and Ti -mediated reductive radical cyclization of epoxy-allene.

Site-Specific Photochemical Desaturation Enables Divergent Syntheses of Illicium Sesquiterpenes

“…At this stage, we achieved the most challenging transformation in the synthesis: a mild photoinduced desaturation in a complex hydrocarbon system. This success eliminated the protection manipulation of the labile C7 alcohol, which usually occurred in the previous synthetic efforts. − The spectroscopic data of 6 are consistent with those reported . Interestingly, masking the C-7 alcohol as an acetate only led to the corresponding olefin product with a moderate yield (see the Supporting Information for more details).…”

“…To date, over 100 sesquiterpenes with diverse oxygenation patterns have been discovered from this genus of plants and display notable biological activities, including antiviral, neurotoxic, and neurotrophic effects. Among them, (−)-merrilactone A ( 7 , Figure C) (anislactone type), which exhibited prominent neurotrophic activities at remarkably low concentrations (100 nM), has received the most attention from the synthetic community with several creative syntheses reported. − Although these sesquiterpenes hold the promise for the treatment of neurodegenerative disorders associated with Alzheimer’s and Parkinson’s diseases, most biological studies are restricted to cell-culture-based assays due to low natural product abundance and limited choices of synthetic derivatives. − Moreover, the molecular mechanism underlying the neurotrophic effect of Illicium sesquiterpenes remains unclear. Here, we disclose a unique site-selective desaturation strategy to access five anislatone-type Illicium sesquiterpenes ( 7 – 11 , Figure C) from inexpensive ( R )-pulegone, including a 13-step synthesis of (−)-merrilactone A ( 7 ) on a gram scale.…”

“…To address these challenges, an efficient synthesis of 5 is necessary. The highly congested five-membered B-ring comprising four contiguous quaternary centers has constituted the critical challenge in the syntheses of related natural products. − We expected that the 15-carbon framework of 5 could arise through a series of annulations from the inexpensive commodity chemical ( R )-pulegone ( 13 , $600/kg). Overall, the site-selective desaturation is the key to achieve a chiral pool approach to these family natural products.…”

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

“…Over the years, several different routes towards the total synthesis of merrilactone A have been reported [77,78,79,80,81]. Most recently, Liu and Wang [82] designed and achieved a concise synthesis of merrilactone A in a racemic form (Scheme 6). In their synthesis work, exploiting dimethyldioxirane (DMDO) on 27 allowed the epoxide intermediate that was subjected to acidic conditions to afford synthetic merrilactone A through the epoxide-opening oxetane formation.…”

Synthesis of Illisimonin a Skeleton by Intramolecular Diels–Alder Reaction of Ortho-Benzoquinones and Biomimetic Skeletal Rearrangement of Allo-Cedranes

“…Due to their biological activity and complex molecular structure, these compounds have attracted the interest of synthetic chemists. Numerous total syntheses and synthetic studies of these compounds have been reported, especially in the last decade [10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Illisimonin A (5), isolated from Illicium simonsii in 2017, is a new sesquiterpene that has a neuroprotective effect on oxygen-glucose deprivation-induced cell injury [24].…”