Lefamulin acetate

Its structure is based on natural pleuromutilin as the parent nucleus (modified by parent nucleus intermediates such as CAS 31716-01-5), and a chiral piperidine thioether side chain (provided by chiral side chain intermediates such as CAS 1350636-87-1) is introduced via side chain coupling reaction. The 8 chiral centers are precisely locked in configuration, which not only retains the targeted binding ability of the parent nucleus to bacterial ribosomes, but also expands the antibacterial spectrum and improves in vivo metabolic stability through side chain modification.

In terms of mechanism of action, Lefamulin acetate targets the 50S ribosomal subunit of bacteria, specifically inhibits peptidyl transferase activity and blocks the whole process of bacterial protein synthesis. Due to its different target from traditional antibiotics such as β-lactams and quinolones, it has no cross-resistance, and still exhibits potent antibacterial activity against common multidrug-resistant pathogens such as multidrug-resistant Streptococcus pneumoniae, Mycoplasma pneumoniae and Chlamydia pneumoniae.

It is indicated for community-acquired bacterial pneumonia (CABP) in adults, covering typical pathogens (Streptococcus pneumoniae, Haemophilus influenzae) and atypical pathogens (Mycoplasma, Chlamydia, Legionella). Clinically, oral or intravenous administration can be selected according to the patient's condition, with oral bioavailability up to 85% and a short treatment course (5-7 days), which can quickly relieve symptoms.

It has a broad and targeted antibacterial spectrum, with inhibitory effects on core pathogens of community-acquired pneumonia, and also has activity against some methicillin-resistant staphylococci. In terms of safety, adverse reactions are mainly mild gastrointestinal discomfort, without severe hepatorenal toxicity, and the risk of drug-drug interactions is low, suitable for special populations such as the elderly and patients with underlying diseases.

For industrial production and quality control, it requires chemical purity ≥ 99.5% and chiral purity (ee value) ≥ 99.5%. It should be sealed and stored in a refrigerated environment at 0-8℃, protected from light and isolated from air to prevent oxidation of the parent nucleus ketone group or deterioration of the side chain thioether bond, ensuring the stability of efficacy. Meanwhile, it can be used as a reserve drug against drug-resistant bacteria for combating drug resistance in community-acquired pneumonia.