Quick wins for a faster PC:
Scan for outdated or missing drivers - takes under a minuteDriver Scan →Repair Windows errors before they cause bigger problemsFix Now →A 2011 synthesis by Tyler A. Davis and Jeffrey N. Johnston used a chiral bis(amidine) catalyst to control the stereochemistry of a key bond-forming reaction on the route to (−)-Nutlin-3. The work reported high selectivity for the reaction and improved the isolated material’s stereochemical purity by fractional recrystallization. It describes a laboratory synthesis—not evidence that Nutlin-3 is an approved cancer treatment or that this route is current commercial manufacturing practice.
What compound was the synthesis designed to make?
(−)-Nutlin-3 is a cis-imidazoline small molecule that inhibits the interaction between p53 and MDM2. Davis and Johnston described it as a cell-biology probe and noted its place in drug development at the time of publication. That 2011 description does not establish its current clinical or regulatory status.
| # | Preview | Product | Price | |
|---|---|---|---|---|
| 1 |
|
Organic Chemistry | $125.24 | Buy on Amazon |
| 2 |
|
Organic Chemistry (MasteringChemistry) | $319.99 | Buy on Amazon |
| 3 |
|
Organic Chemistry as a Second Language: First Semester Topics | $76.48 | Buy on Amazon |
| 4 |
|
Organic Chemistry | $65.32 | Buy on Amazon |
| 5 |
|
Organic Chemistry I For Dummies (For Dummies (Math & Science)) | $11.48 | Buy on Amazon |
As an Amazon Associate I earn from qualifying purchases.
The paper’s focus was a stereoselective synthetic route: making the desired three-dimensional arrangement of atoms reliably, rather than simply forming the compound’s connections. The authors reported their results in Chemical Science, volume 2, pages 1076–1079.
The Tool Desk
Outbyte Driver Updater FREEScan for outdated or missing drivers - takes under a minuteDriver Scan →Outbyte PC Repair FREEClear out junk files and repair common Windows errorsFree Scan →How did the key stereoselective step work?
The central reaction was a catalytic aza-Henry reaction, also called a nitro-Mannich reaction. It joined an aryl nitromethane pronucleophile with an aryl aldimine. A chiral bis(amidine) catalyst helped direct the reaction toward the desired stereochemical arrangement.
#1 Best Overall
This bond-forming step produced differentially protected cis-stilbene diamines. The authors describe reaching these intermediates in two steps; the chemistry provided the foundation for their enantioselective synthesis of (−)-Nutlin-3. The reported selectivity belongs to the optimized addition, not to the overall yield of the complete synthesis.
What selectivity did the authors report?
For the optimized addition, Davis and Johnston reported a 13:1 diastereomer ratio (dr), 91% enantiomeric excess (ee), and nearly quantitative yield. These are the authors’ experimental results as published in 2011, not independently replicated measurements or a yield for the full route.
Rank #2
They then used fractional recrystallization to improve stereochemical purity. The resulting material had a reported diastereomer ratio greater than 200:1 and 97% ee. Recrystallization improved those selectivity figures; it should not be confused with the catalytic reaction itself.
Why was the catalyst important?
The challenge was to control both diastereoselectivity—the relative arrangement of stereocentres—and enantioselectivity, which distinguishes mirror-image forms. The authors identified an electron-rich chiral bis(amidine) as the key to achieving both in the aza-Henry variant. Their article abstract characterized the work as the first highly diastereo- and enantioselective additions of aryl nitromethane pronucleophiles to aryl aldimines.
The significance is therefore methodological: the reaction offered a way to build a useful cis-diamine framework with substantial stereochemical control. The reported metrics describe this study’s optimized conditions, not a head-to-head comparison with other catalysts or routes.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.What the report does—and does not—establish
- It establishes: Davis and Johnston reported a chiral bis(amidine)-catalyzed aza-Henry addition and the selectivity figures measured for their optimized reaction and recrystallized material.
- It does not establish: that Nutlin-3 is an approved cancer medicine, what its current clinical or regulatory status is, or whether the 2011 route is used in commercial manufacturing today.
The article’s bibliographic record is also listed by PubMed. Contemporary coverage included the Royal Society of Chemistry and Chemistry World.
Quick Recap
Best Value
Rank #4
Product prices and availability are accurate as of the date/time indicated and are subject to change. Any price and availability information displayed on Amazon at the time of purchase will apply.
