Josamycin
[CAS# 16846-24-5]

Identification

• Classification: API >> Antibiotics >> Macrolide drug
• Name: Josamycin
• Synonyms: Kitasamycin A3; Turimycin A5; Vilprafen; Wilprafen
• Molecular Formula: C₄₂H₆₉NO₁₅
• Molecular Weight: 827.99
• CAS Registry Number: 16846-24-5
• EC Number: 240-871-6
• SMILES: C[C@@H]1C/C=C/C=C/[C@@H]([C@@H](C[C@@H]([C@@H]([C@H]([C@@H](CC(=O)O1)OC(=O)C)OC)O[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)C)O[C@H]3C[C@@]([C@H]([C@@H](O3)C)OC(=O)CC(C)C)(C)O)N(C)C)O)CC=O)C)O

Properties

• Solubility: Slightly soluble (2.8 g/L) (25 ºC), Calc.^*
• Density: 1.20±0.1 g/cm³ (20 ºC 760 Torr), Calc.^*
• Melting point: 131.5 ºC^**
• Boiling point: 877.8±65.0 ºC 760 mmHg (Calc.)^*
• Flash point: 484.7±34.3 ºC (Calc.)^*
• Index of refraction: 1.535 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

^** "PhysProp" data were obtained from Syracuse Research Corporation of Syracuse, New York (US)

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302
• Precautionary Statements: P264-P270-P301+P317-P330-P501

Discovory and Applicatios

Josamycin is a macrolide antibiotic produced by the bacterium *Streptomyces narbonensis*. It belongs to the 16-membered macrolide family and was first isolated in the 1960s. Josamycin has been used in clinical practice primarily in Europe and parts of Asia for the treatment of bacterial infections, particularly those involving the respiratory tract, skin, and soft tissues. Unlike the more widely known 14-membered macrolides such as erythromycin and clarithromycin, josamycin displays unique pharmacokinetic and microbiological properties that offer therapeutic advantages in specific contexts.

The compound exerts its antibacterial effect by binding to the 50S subunit of the bacterial ribosome. This interaction inhibits protein synthesis by preventing the translocation step in translation, ultimately leading to the cessation of bacterial growth. Josamycin is generally bacteriostatic, though it may exhibit bactericidal activity at higher concentrations against susceptible organisms. Its spectrum of activity includes Gram-positive bacteria such as *Streptococcus pneumoniae*, *Streptococcus pyogenes*, and *Staphylococcus aureus*, as well as atypical pathogens including *Mycoplasma pneumoniae*, *Chlamydophila pneumoniae*, and *Legionella pneumophila*.

One distinguishing feature of josamycin is its efficacy against macrolide-resistant strains of certain bacteria. It retains activity in some cases where resistance to 14- and 15-membered macrolides has developed, particularly due to differences in ribosomal binding or reduced susceptibility to efflux mechanisms. This has made josamycin a valuable option in settings where resistance to other macrolides compromises standard treatment protocols.

Josamycin is administered orally, most often as josamycin propionate, which is better absorbed and more stable than the free base. Following administration, it reaches high concentrations in tissues such as the lungs, tonsils, and skin. This tissue distribution is consistent with its clinical use in treating infections in these sites. It is metabolized in the liver and excreted primarily in the bile, with minimal renal clearance. The relatively long half-life allows for twice-daily dosing in most cases, which enhances patient adherence.

In clinical use, josamycin has demonstrated efficacy in the treatment of pharyngitis, tonsillitis, sinusitis, bronchitis, and pneumonia. It has also been employed for skin infections, acne vulgaris, and certain sexually transmitted infections, including *Chlamydia trachomatis*. Its tolerability profile is generally favorable, with fewer gastrointestinal side effects compared to erythromycin. Additionally, josamycin is considered safe for use during pregnancy, making it an option for treating infections in pregnant women when other antibiotics are contraindicated.

Despite its established role in antimicrobial therapy in several countries, josamycin has not been widely approved or marketed in the United States. This may be due to market competition, regulatory differences, or the dominance of other macrolides with similar spectrums of activity. However, in countries where it is available, josamycin continues to be a valuable component of the macrolide class, particularly in the context of antibiotic resistance.

The development and sustained use of josamycin underscore the importance of diversifying antibiotic options within existing classes to combat emerging resistance and to tailor therapy to specific clinical needs. Its role in treating infections caused by atypical and resistant pathogens highlights its continued relevance in modern medicine.

References

1975. The Macrolide Antibiotics. Mechanism of Action of Antimicrobial and Antitumor Agents.
DOI: 10.1007/978-3-642-46304-4_30

2024. Macrolides and Diseases Associated with Loss of Epithelial Barrier Integrity. Macrolides as Immunomodulatory Agents.
DOI: 10.1007/978-3-031-42859-3_1

2024. Chinese advances in understanding and managing genitourinary tract infections caused by Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma urealyticum. Archives of Microbiology, 206(12).
DOI: 10.1007/s00203-024-04204-z