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Research

 

 
ASYMMETRIC CATALYSIS
 

New Electronic Helix Theory-Guided Rational Design of Asymmetric Catalytic Systems: We recently developed a new electronic helix theory for molecular chiralities and chiral interactions. It shows that complex molecular chiralities can be generalized on the basis of their inherent electronic helicities, and that the fundamental principle underlying chiral induction and recognition is the conservation of helical asymmetry, i.e., a chiral catalyst or host preferentially induces or recognizes chirality of the same helicity. The theory agrees well with all the major experiments reported since the birth of asymmetric synthesis in 1960s, accommodates results that conventional steric theories cannot, and promises predictive power. From a conceptually novel scenario, it reveals that effects in stereochemical control conventionally attributed to steric hindrance instead have an electronic basis. Despite tremendous progress achieved in enantioselective catalysis in the past several decades, endeavors in this frontier field remain largely empirical. The hallmark of our program will therefore keenly focus on demonstrating how this electronic theory could guide design and discovery of broadly useful enantioselective processes from a more rational approach. 

 
 
 
Please check our PUBLICATION webpage for exciting latest studies on new insights and discoveries on enantioselective catalysis enabled by this theory.
 
 
NATURAL PRODUCTS SYNTHESIS
 
Total Synthesis of Bioactive Natural Products: Another particular emphasis of our program is to explore conceptually novel strategies for efficient total chemical synthesis of natural products that possess considerable stereochemical complexity and significant therapeutic values. The target molecules completed or under our current concern are Longeracinphyllin A, Daphnilongeranin B, Linderaspirone A, Bi-linderone, Fumitremogin A, Swweilactone A, and Lycojapodine. 
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Summarized below are some significant progresses we have achieved recently.  
 
The Daphniphyllum class of alkaloids stands out from a large pool of fascinating natural products uncovered in recent years for their highly impressive structural diversities, stereochemical complexities, and skeletal novelties. Within this class two compounds, Longeracinphyllin A and Daphnilongeranin B structured below as 1 and 5 respectively, attracted our particular attention. An inspection of their architectures reveals that 1 seems suspiciously to be a Diels-Alder-type adduct assembled from a diene alkaloid component 3 and an iridoid glycoside dienophile 4. Fairly unusually, a team led by Professor Xiaojiang Hao from the Chinese Science Academy’s Kunming Institute of Botany isolated and identified 1, its Diels-Alder-type regio-isomer 6, 4, and 3’ oxidative analog 5 all from the same plant source! This discovery provides a new and highly promising platform on which the existence of so-called Diels-Alderase, a long-debated topic, might be further probed. 
 
 
 
 Our goals are to make 3 thus complete a total synthesis of 1 through its cycloaddition with 4 and to prove or disprove the concerted-versus-stepwise reaction pathway via kinetic isotope effect investigations. Central to the success of our mission is exploring an efficient and robust strategy that can lead to total synthesis of 5. With key strategies described below, we have recently succeeded in the construction of the [5-6-7] Tricyclic (published) and the [6-5-6-7] Tetracyclic Ring Skeleton of Calyciphylline Alkaloid Daphnilongeranin B.
 
 
 
 Linderaspirone A and Bi-linderone are two recently discovered and biologically meaningful natural products featuring unique spirocyclopentenedione skeletons that have long eluded identifications from traditionally acclaimed Lindera species medical plants. A close inspection of their dimeric stereochemical architectures helped us to subsequently discover that a simple exposure to sunlight is sufficient for triggering photochemical reaction cascades in the naturally occurring monomer methyl linderone, thus leading to remarkably efficient biomimetic total syntheses of both of them. 
 
 
 

 The study also mechanistically elucidated fascinating photochemical [2+2] cycloaddition-Cope or radical rearrangement cascades in the corresponding  π-π stacked dimerized substrates, thus leading to substantial revisions of their reported biosynthetic pathways.