strategic design; Natural product; new reaction; total synthesis; Alkaloid
Li Guang, Piemontesi Cyril, Wang Qian, Zhu Jieping (2019), Stereoselective Total Synthesis of Eburnane-Type Alkaloids Enabled by Conformation-Directed Cyclization and Rearrangement, in Angewandte Chemie International Edition
, 58(9), 2870-2874.
Torres-Ochoa Rubén O., Buyck Thomas, Wang Qian, Zhu Jieping (2018), Heteroannulation of Arynes with α-Amino Imides: Synthesis of 2,2-Disubstituted Indolin-3-ones and Application to the Enantioselective Total Synthesis of (+)-Hinckdentine A, in Angewandte Chemie International Edition
, 57(20), 5679-5683.
Piemontesi Cyril, Wang Qian, Zhu Jieping (2016), Enantioselective Synthesis of (+)-Peganumine A, in Journal of the American Chemical Society
, 138(35), 11148-11151.
Natural products are biosynthesized to interact with multiple proteins as substrates and targets. It is therefore not surprising that they are the best sources of drugs and drug leads. In spite of the great success of natural products in the history of drug discovery, they are significantly underrepresented in current small molecule libraries due presumably to: a) extremely low natural abundance, hence limited supply; b) enormous difficulties in structural modifications due to their molecular complexity; c) lack of practical synthesis.As a strong ally of natural products, total synthesis often provides intermediates and chemical tools that allow modification of the structure of natural products. Such changes can improve biological and physical properties of the parent compound, help understanding the structural-activity relationship (SAR) and eventually identifying a simplified, hence more accessible, analogue with equal or even better pharmacological properties for drug development. Recent crowning achievements in this arena are the development of Taxotère® and eribulin (Halaven®) both are marketed anti-cancer drugs. On the other hand, the analogue synthesis can also play important role in identifying the natural product’s macromolecular target.Traditionally, organic compounds are synthesized via stepwise construction of individual chemical bond found in the target molecules with a work-up procedure after each transformation. The increase of molecular complexity per operation with such a strategy is therefore incremental. Searching for multiple-bond forming reactions and minimizing non-constructive transformations is therefore of increasing importance in designing of synthesis strategy/tactics. Such strategy could not only shorten the synthetic sequence, but also enhance the aesthetic appeal of the synthesis endeavor. The goal of this project is to develop new reactions and strategies allowing a rapid access to skeletally diverse and complex polycyclic structures. It consists of a)To develop a Pd-catalyzed enantioselective decarboxylative vinylation/arylation of racemic 2-substituted arylacetic acids and to develop an asymmetric synthesis of (-)-vallesamidine and (-)-strempeliopine.b)To develop an enantioselective total synthesis of (-)-alstilobanine C and (-)-undulifoline involving a key integrated oxidation/reduction/cyclization sequence (iORC process).c)To develop a new intramolecular oxidative coupling of isocyano-aldehyde for the synthesis of macrocyclic ketoamides and to develop an enantioselective total synthesis of (-)-peganumine A.d)To investigate the Structure-Activity Relationship (SAR) of aforementioned natural products as well as their synthetic analogues.