The birth of Morken reaction

Discovery and development of Pd-catalyzed cross-coupling reactions greatly spurred the rise of medicinal chemistry. They also strongly biased the chemical space of potential drugs to biaryl-like compounds. Currently, directed by growing demand for chemical diversity, the field is evolving in the direction of more flexible chemotypes, where rigid scaffolds are connected via single Csp3-Csp3 bonds.

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Some things organic chemists should borrow from bio lab

Since I’ve shifted from ‘pure’ synthetic chemistry lab to chemical biology, my set of labware has also changed from borosilicate glassware to polypropylene plasticware. And, you know what, I wish it happened years earlier. Here are some awesome little things that make my synthetic life easier today. Continue reading “Some things organic chemists should borrow from bio lab”

Retrosynthesis ex machina

A Christmas present from one of the bastions of modern organic synthesis appeared in Nature. The idea of automated retrosynthetic analysis bugged the greatest OC minds since EJ Corey came up with the very concept of retrosynthesis. Back in 1969 Corey and Wipke set the stage by publishing a paper in Science.

corey_CAOS
Screenshot of the title and the whole abstract of the 1969 Science paper. Source

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OC tidbits #1

Despite deromantizing total synthesis I do like organic chemistry and do feel aesthetic pleasure from synthetic schemes and mechanisms [note for my future employer, I do enjoy the bench work, too!]. Also, since high school and undergrad years I still have weak spot for org-chem puzzles. So Below are some little nuggets (subjective, of course) from the recent OC papers that I found interesting.

  • From Popov et al (Somfai lab) (ACIE):

  1. Try to figure out the mechanismacie9-10
  2. Try to explain the difference in chemoselectivity (and what’s going on with that Ts group by the way?).acie10-11acie10-12

 

  • From Hamasaki et al (Kochi lab) (JACS)

Can you guess the mechanism for this one?

chain-walking-nowarning

  • Dream big!

All multi-ton processes start from the small scale, check this cute Kugelrohr apparatus setup by Thiyagarajan et al. for processing of biomass-derived furans (The white stuff in the middle is a zeolite catalyst; ACIE)

kugelrohr.png

Antiviral sugar superballs

superball

It’s not too common to encounter a compound as one above in a paper tagged ‘medicinal chemistry’. But the team of Spanish and French chemists seems not to care too much about rule of 5 or any other rules of thumb that constrain their creativity. Especially when the rationale for compound design was:

it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses

The ligands dubbed ‘superballs’ are targeting dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). And the multivalency of ligand-receptor interaction is the key factor of viral infection. Previous state-of-the-art ligands were virus-like particles with 1620 mannoses displayed on their surface. So I guess in this study authors significantly optimized ligand efficiency. Continue reading “Antiviral sugar superballs”

What’s so special about synthesis?

On Tuesday a piece form Phillip Ball appeared in Nature, with provocative question ‘Why synthesize?’ addressed to organic chemists, and particularly to adepts of total synthesis. And, you know what, after reading it, I didn’t feel like the author answered the question − for each argument he provides a counterargument. So the take home message I got was the following:

even though molecule-building is sure to remain a crucial part of the chemical enterprise, conventional organic synthesis need not be the only, or even the best, way to do it

When I started learning about organic chemistry, the book “Organic synthesis: the science behind the art” was one of the strongest inspiration sources for the subsequent choice of the major. This perception of the organic synthesis as the art is something that triggered my interest but what’s causing awkward feelings nowadays.

Like architecture, chemistry deals in elegance in both design and execution.

What exactly is meant by “elegance” of synthesis? “Beauty is in the eyes of the beholder” says the old proverb. So isn’t it disturbing that organic chemists themselves are the only ones who appreciate the elegance of total synthesis?

In my current opinion arranging synthetic steps in a reasonable manner is an engineering and project management problems, but by no means is it the art. There’s no more elegance in designing the synthetic scheme than in designing any other sophisticated multi-step experiment. So why don’t call microbiology the art, too? Why setting up the culturing of stubborn microorganisms producing natural products is different? After all, it’s often the same trial and error process yield a couple milligrams of the product in the end.

For me the synthesis is a means, not the goal. It’s a chemist’s way of solving problems. But other scientists may be interested in solving the same problems, too. So indeed, the synthesis is not the only and often not the best way to do it. That’s why chemists should focus on how to make it the best way. In this I’m staying with George Whitesides’s philosophy that simplicity should be the major goal. But that doesn’t make organic chemists unique among other scientists. That’s why I’d rephrase the following quote from Phillip Ball:

We need to avoid romanticizing an imagined bygone age […]

We [organic chemists] need to avoid romanticizing an imagined uniqueness of our field and train a broader look on problem solving.

science_Art

Rational serendipity for drug design

With all modern advances and super-sexy scientific tools we currently have, randomness is still arguably the best source of truly innovative discoveries. And scientists do acknowledge that, so various “accelerated serendipity” techniques are flourishing in drug discovery, organic chemistry, chemical biology, and other fields. Continue reading “Rational serendipity for drug design”

PSYCHEDELIC 2DJ NMR

Although originally developed by physicists, NMR is one of those technologies that revolutionized chemistry. With enormous recent advances, it became a great tool for interrogating complex structures of peptides and nucleic acids. But there’s still plenty of room for improvement in the most basic its application, proton (1H) NMR. Continue reading “PSYCHEDELIC 2DJ NMR”