Chlortetracycline hydrochloride
[CAS# 64-72-2]

Identification

• Classification: API >> Antibiotics >> Tetracycline
• Name: Chlortetracycline hydrochloride
• Synonyms: [4S-(4alpha,4aalpha,5aalpha,6beta,12aalpha)]-7-Chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride
• Molecular Formula: C₂₂H₂₃ClN₂O₈^.HCl
• Molecular Weight: 515.35
• CAS Registry Number: 64-72-2
• EC Number: 200-591-7
• SMILES: CN(C)[C@@H]1C(O)=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)ccc(Cl)c4[C@@](C)(O)[C@H]3C[C@@H]12.Cl

Properties

• Solubility: water: ~8.6 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H317-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P272-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin sensitization	Skin Sens.	1	H317
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H302
Flammable liquids	Flam. Liq.	3	H226
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1A	H314
Aspiration hazard	Asp. Tox.	2	H305
Reproductive toxicity	Lact.	-	H362
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H312
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Reproductive toxicity	Repr.	1B	H360

Discovory and Applicatios

Chlortetracycline hydrochloride is a semisynthetic salt form of chlortetracycline, one of the earliest members of the tetracycline class of antibiotics. It is a low-molecular-weight organic compound produced on an industrial scale and formulated primarily for pharmaceutical and veterinary use. Its chemical structure is based on the polycyclic tetracycline scaffold bearing a chlorine substituent, which contributes to its antibacterial spectrum.

The discovery of chlortetracycline dates to the late 1940s, during an intensive period of antibiotic screening focused on soil-derived microorganisms. The compound was first isolated from cultures of Streptomyces aureofaciens, a filamentous bacterium identified through systematic testing of fermentation broths for antimicrobial activity. Chlortetracycline was notable as the first tetracycline antibiotic to be discovered and was originally referred to as aureomycin. Its isolation represented a major advance in natural product chemistry and antibiotic research, as it demonstrated that a single compound could exhibit broad-spectrum activity against both Gram-positive and Gram-negative bacteria.

Following its discovery, chlortetracycline was rapidly developed for clinical use. Conversion to the hydrochloride salt improved its stability and handling properties, facilitating formulation for oral and parenteral administration. Early clinical studies confirmed its effectiveness against a wide range of bacterial infections, including respiratory tract infections, urinary tract infections, and certain zoonotic diseases. Its broad activity was attributed to inhibition of bacterial protein synthesis through binding to the 30S ribosomal subunit, a mechanism that later became characteristic of the entire tetracycline class.

In addition to human medicine, chlortetracycline hydrochloride found extensive application in veterinary medicine. It has been widely used for the treatment and prevention of infectious diseases in livestock and poultry, particularly those caused by susceptible bacteria such as Escherichia coli, Pasteurella, and Mycoplasma species. The compound has also been employed as a feed additive in certain regulatory environments, where it contributed to disease control and growth promotion, although such uses have been increasingly restricted due to concerns about antimicrobial resistance.

From a manufacturing perspective, chlortetracycline hydrochloride is produced by large-scale fermentation followed by multistep purification and salt formation. Advances in fermentation technology and downstream processing during the mid-twentieth century enabled reliable industrial production, making the compound widely accessible and economically viable. These developments also laid the groundwork for the subsequent discovery and modification of related tetracycline antibiotics, including oxytetracycline and tetracycline itself.

Although newer antibiotics with improved pharmacokinetic profiles have reduced the prominence of chlortetracycline in human medicine, it remains an important compound historically and practically. Its discovery established the tetracycline scaffold as a versatile and valuable platform in antibiotic chemistry, and its continued veterinary use underscores its enduring relevance. Chlortetracycline hydrochloride therefore occupies a significant place in the history of antimicrobial agents, bridging early natural product discovery and modern antibiotic development.

References

Chopra I, Roberts M (2001) Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiology and Molecular Biology Reviews 65 2 232–260 DOI: 10.1128/MMBR.65.2.232-260.2001

Nelson ML, Levy SB (2011) The history of the tetracyclines. Annals of the New York Academy of Sciences 1241 1 17–32 DOI: 10.1111/j.1749-6632.2011.06354.x