What molecule am I?
Doxycycline1 is a venerable antibiotic that was first described in 1958 by Charles R. Stephens and co-workers at Pfizer (Groton, CT). They used catalytic hydrogenolysis of a hydroxyl group in tetracycline2 to produce a series of antimicrobial 6-deoxytetracylines, one of which, α-6-deoxy-5-hydroxytetracycline (α-6-DHT), later became known as doxycycline.
In the ensuing years, much more was discovered about 6-deoxytetracyclines.
- 1960: J. R. D. McCormick and colleagues at American Cyanamid (Pearl River, NY) explored the relationship between structure and antibacterial activity in 6-deoxytetracyclines.
- 1962: Stephens et al. at Pfizer studied how the configuration at C6 of 6-deoxytetracyclines affected antibiotic performance against the bacterium Klebsiella pneumoniae; α-6-DHT proved to be the most potent.
- 1963: The Stephens group expanded on the preparation (including side reactions), C6 stereochemistry, and structure–activity data of 6-deoxytetracyclines, again including α-6-DHT.
Doxycycline was approved as a broad-range antibiotic by the US Food and Drug Administration in 1967. It is used to treat bacterial infections ranging from acne to malaria to syphilis to tick-borne pathogens such as cause Lyme disease. It can be administered orally or intravenously. Doxycycline is commercially available as its monohydrate2 and its hyclate3, both of which release doxycycline in the body.
1. SciFindern name: 2-naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, (4S,4aR,5S,5aR,6R,12aS)-.
2.CAS Reg. No. 17086-28-1.
3.CAS Reg. No. 24390-14-5; “hyclate” is a pharmaceutical term for hydrochloride hemiethanolate hemihydrate.
Doxycycline hazard information*
| Hazard class** | GHS code and hazard statement | |
|---|---|---|
| Acute toxicity, oral, category 4 | H302—Harmful if swallowed |  |
*No safety data sheets for anhydrous doxycycline are available; data are for the monohydrate.
**Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Explanation of pictograms.
Molecules from the Journals
Sodium nickelate1 (NaNiO2) is a salt with some unusual chemical and physical properties. It was first prepared in 1954, when Lawrence D. Dyer, Bernard S. Borie Jr., and G. Pedro Smith at Oak Ridge National Laboratory (TN) bubbled oxygen through sodium hydroxide in a nickel tube at 800 ºC. In 1994, Arabinda Ray and collaborators at Sardar Patel University (Vallabh Vidyanagar, India) and the University of Poona (India; now Savitribai Phule Pune University) described how diamond crystallizes from a solution of carbon in molten NaNiO2 at ≈850 ºC.
This past October Liam A. V. Nagle-Cocco and Siân E. Dutton at the University of Cambridge (UK) and 11 colleagues in the United Kingdom, the United States, and France described a displacive Jahn–Teller transition in NaNiO2. The authors believe that “this study is the first to show a displacive Jahn–Teller transition in any material using direct observations with local probe techniques.”
Alectinib2 is an oral, highly potent anaplastic lymphoma kinase (ALK) inhibitor for treating ALK-positive non–small-cell lung cancer (NSCLC). It was first described in 2010 by Kazutomo Kinoshita and co-inventors in Japanese patent JP4588121 to Chugai Pharmaceutical (Tokyo).
In October, Tomochiro Oki and a large team of co-workers at Chugai reported the development of a large-scale alectinib manufacturing process. The key to the process was forming the indole-containing tetracyclic core, which was accomplished through an intramolecular reductive cyclization and an intramolecular Friedel–Crafts reaction.
1. CAS Reg. 12164-05-5.
2. CAS Reg. 1256580-46-7.
Molecules from the Journals
MOTW briefly describes noteworthy molecules that appeared in recent ACS journal articles. See this week's
edition.
This molecule was suggested by a reader. We present almost all of the molecules suggested by our readers. If you have a molecule you would like us to consider, please send us a message. And thank you for your interest in Molecule of the Week! —Ed.
Doxycycline fast facts
| CAS Reg. No. | 564-25-0 |
| Empirical formula | C22H24N2O8 |
| Molar mass | 444.44 g/mol |
| Appearance | Yellow crystals or powder |
| Melting point | 201 °C |
| Water solubility | 0.3 g/L (25 ºC) |
Learn more about this molecule from CAS, the most authoritative and comprehensive source for chemical information.
Molecule of the Week needs your suggestions!
If your favorite molecule is not in our archive, please send us a message. The molecule can be notable for its current or historical importance or for any quirky reason. Thank you!
Stay Ahead of the Chemistry Curve
Learn how ACS can help you stay ahead in the world of chemistry.
