What’s actually slowing this PC down?
Pick the symptom - the matching free tool is one click away.
iTechGuides is reader-supported. When you buy through links on our site, we may earn an affiliate commission. As an Amazon Associate I earn from qualifying purchases. Learn more
Davis and Johnston’s 2011 synthesis of (−)-Nutlin-3 used a chiral bis(amidine)-catalyzed aza-Henry reaction to control the stereochemistry of a key intermediate. In their optimized reaction, they reported a 13:1 diastereomer ratio (dr), 91% enantiomeric excess (ee), and nearly quantitative yield; fractional recrystallization improved the isolated material to greater than 200:1 dr and 97% ee. These results concern the reported addition and its purification, not the yield of the complete synthesis.
What compound did the synthesis target?
The target was (−)-Nutlin-3, 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. Their 2011 synthesis report 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 |
The chemistry addressed a specific challenge: preparing the target’s chiral, cis-configured framework with control over which stereoisomers formed.
Do these 3 things before closing this tab:
1Clear out junk files and repair common Windows errors2Scan for outdated or missing drivers - takes under a minute3Repair Windows errors before they cause bigger problemsHow did the key stereoselective reaction work?
The central bond-forming step was a catalytic aza-Henry reaction, also known as a nitro-Mannich reaction. An aryl nitromethane pronucleophile added to an aryl aldimine, forming a carbon–carbon bond and building a differentially protected cis-stilbene diamine intermediate.
#1 Best Overall
An electron-rich chiral bis(amidine) catalyst was central to the selectivity. By using a chiral catalyst to guide the addition, the authors obtained both diastereo- and enantioselectivity. They reported that the intermediate chemistry furnished differentially protected cis-stilbene diamines in two steps; that sequence underpinned the enantioselective synthesis of (−)-Nutlin-3.
What selectivity and yield did the authors report?
For their optimized addition, Davis and Johnston reported a 13:1 dr, 91% ee, and nearly quantitative yield. Fractional recrystallization then enriched the material to greater than 200:1 dr and 97% ee. The first set of values describes the optimized addition; the higher selectivity figures describe material after recrystallization. Neither yield figure should be read as the yield of the complete synthesis.
Rank #2
These are the authors’ reported experimental results in the 2011 paper, not independently replicated measurements. The improvement after recrystallization also illustrates the distinction between selectivity generated in a reaction and the stereochemical purity achievable after purification.
What does this result establish—and what does it not?
The paper established a stereoselective synthetic route to a useful chiral intermediate and applied that chemistry to an enantioselective synthesis of (−)-Nutlin-3. Its significance is in the reaction design and stereochemical control, rather than in evidence of a treatment’s clinical benefit.
- It is a laboratory synthesis report, not evidence that Nutlin-3 is an approved cancer treatment.
- It does not establish that this route is current commercial manufacturing practice.
- The 2011 description of the compound’s development status should not be treated as a statement about its status today.
Where was the synthesis published?
The report by Tyler A. Davis and Jeffrey N. Johnston appeared in Chemical Science, volume 2, pages 1076–1079, in 2011. The Royal Society of Chemistry article is available at doi:10.1039/C1SC00061F; PubMed provides a bibliographic record at PubMed.
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.
