In Memory of Dr. Congyuan Guo (郭聪元, 1948 - 2005)

One of my beloved teachers Dr. Conyuan Guo (郭聪元) has left us in 2005.  The deep impression he made on me and short amount of time we spent together in the early 1980s is not at all proportional. It was he who introduced me into the study of reaction mechanism through kinetic. His technical skills and knowledge in chemistry, especially kinetic isotope effect (KIE), quantum mechanical tunnelling were at the forefront of the field. Unfortunately, directly or indirectly due to some incidents of his professor at Rutgers, Guo left the field and switched to analytical chemistry (PhD, Univ. of Missouri) where again he had a very successful career as an analytical chemist. I always remember him fondly over the last 30 years. I love his super friendly and down to earth demeanor, his practicality as a scientist and a friend, his sense of humor and even his distinct Tangshan accent. 

I wish him rest in peace!

Amazing Structural Similarity: Linezolid and Rivaroxaban

Factor Xa inhibitor Xarelto, developed as a new anticoagulant, has a really amazing structural similarity to Zyvox, BUT it does not have antibacterial activity against Gram positive pathogens as most oxazolidinones do. This pair should be used as an excellent example to teach "Similarity". Be open minded, only SAR can guide you!

   

Design Simplicity of Telbivudine

As a medicinal chemist, I am sure you would appreciate the simplicity of design. Here is an excellent example of an antiviral drug used in treating Hepatitis B, Tyzeka (Telbivudine).  It is “just” the L-isomer of thymidine-that is it. The drug was marketed by Novartis (licensed from Idenix, a company was bought out by Merck in 2014). It relived the disease burden in thousands and thousands of patients, and generated millions of millions of dollars since its approval in 2006. Thanks to the discovery from Professor Jean-louis Imbach and Dr. Gilles Gosselin’s joined CNRS lab at the University of Montpellier. Their many years of sustained efforts in bioactive molecular chemistry culminated this life saving medicine. What I like here is not only the beauty of product but also the synthetic chemistry to make the drug. Smart application of silicon chemistry (my personal favorites) was a special feature in this paper published in the year 2000  including the use of silicon protection and the use of (TMS)₃Si-H as a reducing agent (radical chemistry). Simplicity does not mean simple, Telbividine’s optimized semi-large scale synthetic sequence has near10 steps from L-Ribose (it’s not the natural D-Ribose).