Chemistry Graduate Seminar

 

Abstract

Preparation of diverse homologs from lead compounds has been a common and important practice in medicinal chemistry. However, homologation of many functional groups, such as ethers and amides, remains challenging. In this talk, deconstructive strategies to enable homologation of ethers and amides are discussed. First, the method involving boron-insertion into alkyl ether bonds is realized through a Ni/Zn tandem catalysis. The organoborinate intermediates allow direct modification of the skeletons of ethers, including ring expansion and O-to-N editing. The reaction goes through a cleavage-and-then-rebound mechanism. This study further inspires the development of modular synthesis of monocyclic 1,2-azaborines, which is an important isostere of benzene. On the other hand, a hook-and-slide strategy for homologation of tertiary amides with tunable lengths of the inserted carbon chain is introduced. Alkylation at the α-position of the amide (hook) is followed by highly selective branched-to-linear isomerization (slide) to effect amide migration to the end of the newly introduced alkyl chain; thus, the choice of alkylation reagent sets the homologation length. The key step involves a carbon–carbon bond activation process by a carbene-coordinated rhodium complex with assistance from a removable directing group. The approach is demonstrated for introduction of chains as long as 16 carbons and is applicable to derivatized carboxylic acids in complex bioactive molecules.

 

Bio

Dr. Guangbin Dong received his B.S. degree from Peking University and completed his Ph.D. degree in Chemistry from Stanford University with Professor Barry M. Trost. In 2009, He joined the group of Prof. Robert H. Grubbs at California Institute of Technology, as a postdoctoral researcher. His expertise is in the field of organic synthesis, catalysis, organometallics and medicinal chemistry. His future research interests lie at the development of powerful chemical tools for addressing questions of biological importance. His research program will bring together the complimentary knowledge of organic synthesis, medicinal chemistry and organometallic chemistry in collaboration with scientists in the field of cellular biology and animal pharmacology to identify effective small-molecule agents that target new molecular mechanisms for cancer treatment.

Dr. Dong’s Ph.D. research studies involved development of new catalytic enantioselective synthetic methods and applied these methods in the total syntheses of biologically important molecules. The majority of the natural products Dr. Dong synthesized exhibit high potent anticancer activity, such as agelastatin A, terpestacin, and bryostatins. In addition, he has designed and synthesized a new bryostatin analogue; in collaboration with Genetech, this agent has shown nanomolar anticancer activity again several cancer cell lines. This work has been published in Nature.

At California Institute of Technology, Dr. Dong was a Camille and Henry Dreyfus Environmental Chemistry Fellow in the group of Professor Robert H. Grubbs. His research aimed at development of catalysts for anti-Markovnikov hydration of olefins, considered as one of the top 10 challenges in catalysis. Dr. Dong developed the first reproducible anti-Markovnikov olefin hydration process using a dual-metal system.

Dr. Dong’s primary goal as an advisor is to give graduate students and postdocs with professional training that will assist them for their future careers as independent researchers. He will create a healthy environment where both students and postdocs are able to share experiences and knowledge with each other. The key is to offer each group member sufficient freedom to explore on his/her own. They should be allowed to make their own mistakes and correct themselves by finding their own solutions. They will be encouraged to talk more to each other and learn from each other. Meanwhile, he will be around and ready to give suggestions. Dr. Dong believes that such a collaborative environment would be beneficial for students and postdocs to develop into thoughtful scientists capable of conducting research on an independent level.