Selected strategies to fight pathogenic bacteria

Figures & data

Scheme 1. Synthesis of eravacycline. (i) LDA, TEA•HCl, THF -70 °C; LiHMDS, -70 °C to -10 °C, 94%; 48% HF, MeCN, rt; (ii) H₂, 5% Pd-C, HCl, MeOH-H₂O, rt, 89%; (iii) 2-(pyrrolidin-1-yl)acetyl chloride hydrochloride, MeCN-H₂O, 10 °C, 89%; (iv) HCl, MeOH, EtOH; EtOAc, quant.

Scheme 2. Synthesis of vaborbactam. (i) TBDMSCl, imidazole, CH₂Cl₂, 94%; (ii) [Ir(COD)Cl]₂, dppb, pinacolborane, CH₂Cl₂, 96%; (iii) (+)-pinanediol, THF; (iv) n-BuLi, CH₂Cl₂, -95 °C, THF; (v) LiHMDS, THF, -78 °C to rt; 2-thiopheneacetic acid, EDCI, HOBT, NMM, CH₂Cl₂, 70%; (vi) 3 M HCl, 1,4-dioxane, Δ, 64%.

Scheme 3. Synthesis of doripenem hydrate. (i) DIPEA, DMF, EtOAc, rt, 88%; (ii) H₂, 10% Pd/C, MgCl₂•6H₂O; crystallisation; sterilisation; crystallisation, 64%.

Figure 1. Antibacterial coniferous diterpenes and their nanocellulose surfaces.

Table 1. Pathogenic bacteria and their CAs, as well as infectious disease they can cause.

Pathogen	CA class	Disease	Infectious
Brucella suis	β and γ	Brucellosis	contagious zoonosis (ingestion of unpasteurised milk or undercooked meat
Vibrio cholerae	α, β and γ	Cholera	severe diarrhoea.
Helicobacter pylori	α, β and γ	Gastritis and gastric ulcers	inflammation of the stomach lining, may lead to gastric cancer
Francisella tularensis	β and γ	Tularemia	debilitating febrile illness
Mycobacterium tuberculosis	β and γ	Tuberculosis	infectious attacking the lungs or other parts of the body.
Clostridium perfringens	β and γ	Food poisoning	death as a result of food poisoning.
Streptococcus pneumoniae	β and γ	Pneumonia	inflammatory condition of the lung
Streptococcus mutans	β and γ	Dental caries	infectious of the dental hard tissues
Salmonella enterica	β	Salmonellosis	diarrhoea, fever, vomiting, and abdominal cramps
Haemophilus influenzae	β	Influenza	nausea, vomiting, gastroenteritis
Porphyromonas gingivalis	β and γ	Periodontitis, rheumatoid arthritis	inflammatory diseases affecting the tissues around teeth; rheumatoid arthritis
Legionella pneumophila	β	Legionellosis	pneumonia
Pseudomonas aeruginosa	β	No particular name	infections in cystic fibrosis patients
Escherichia coli	β and γ	No particular name	diarrhoea (for some pathogenic strains)
Neisseria gonorrhoeae	α	gonorrhoeae	sexually transmitted disease
Enterococcus spp.	β and γ	No particular name	vancomycin resistant enterococci (VRE) involved in nosocomial infections

Figure 2. The nanoparticulate drug delivery systems being explored in antimicrobial therapy.