Today our work on the total synthesis of the araiosamines is out in JACS. While the chemistry (success and unexpected failures) was detailed in the paper and SI, I would like to share some stories from the science behind the construction of these molecules. On the first day I joined the lab, I told Phil that my motivation was to …
We are delighted to announce that our recent work on Fe-catalyzed cross-couplings of redox-active esters (RAEs) has recently been published in JACS! We’d like to share with you how we started out, developed this project, and how things evolved from the first discovery. During the past year our group has been involved in using RAEs as coupling partners in cross-coupling. We …
Greetings and salutations, ladies and gentlemen! Our total synthesis of maoecrystal V has been published in JACS recently. It is a fascinating molecule, in my opinion, with a beautiful array of densely interlocked rings, myriad of quaternary carbons, and an intriguing bioactivity profile to back it up (or not). It is no wonder, that it received so much attention from …
Our total synthesis of Pallambins C and D is out today in JACS. We have placed a summary of our failed approaches and strategies in the supporting information to give the reader a glimpse of what went into developing our synthetic route. Here we highlight a few reactions and problems encountered during this work. Our early approach began with the gamma-arylation of …
When our latest success towards the two-phase synthesis of taxol was published in Angew this month, I experienced both joy and relief. From my first day in the Baran lab, I have spent the entirety of my postdoctoral career on the taxanes – looking back, I fondly recall many behind-the-scene stories in our struggle against these diabolical terpenes. I would like …
This post comes from outside the Baran lab. A very talented undergraduate (Wade Miller) from the University of Pennsylvania sent us his paper from an assignment in philosophy class regarding the relevance of total synthesis in the modern era. It’s a topic near and dear to our hearts and a great read. For those students and postdocs toiling away at a natural …
Despite all of the wonderful advances in organic synthesis, amide-bond formation is still the most widely used reaction among those making medicines. This truth has led some to declare their embarrassment and depression. Medicinal chemist Derek Lowe has a nice post reviewing this state of affairs. The authors of theJ. Med. Chem. piece attribute the “over amide-ification” of medicinal chemistry to the following factors: …
When we look back at some of our lab’s terpene syntheses using a “two-phase” approach, it becomes abundantly clear that one oxidation reaction is used more than anything else: the allylic C–H oxidation. What isn’t obvious just by reading, though, is how unappealing these reactions actually are to perform. In the case of taxayunnanine D, our synthesis required 30 equivalents …
Today, our paper entitled “Nineteen-Step Total Synthesis of (+)-Phorbol” was published online in Nature. The chemistry is thoroughly described in the paper so here I will just briefly highlight a key reaction which led us to success. This concise synthesis was achieved based on our two-phase terpene synthesis strategy. We hypothesized that an ingenol synthesis intermediate shown below would serve …
Since our first report in 2011 on the trifluoromethylation of heterocycles, sulfinate chemistry has been demonstrated to be a useful tool for drug discovery. The lab extended this chemistry beyond trifluoromethyl radicals to a whole host of other useful substituents that medicinal chemists find desirable. We even went as far as to show that one could functionalize caffeine in its native habitat: oolong …