Penamecillin is a semisynthetic penicillin derivative and an acetoxymethyl ester prodrug of benzylpenicillin (penicillin G). It belongs to the beta-lactam penicillin class of antibacterial compounds. Penamecillin is chemically classified as a penicillanic acid ester and is converted by esterases to benzylpenicillin, the pharmacologically active antibacterial agent.
Penamecillin has the CAS Number 983-85-7, molecular formula C19H22N2O6S, and molecular weight 406.45 g/mol. FDA GSRS identifies the substance under UNII H0P1YE5581, while ChEBI, ChEMBL and DrugBank provide additional chemical and pharmaceutical identifiers.
The compound is also known by several names, including Penamecillinum, Penamecillina, benzylpenicillin acetoxymethyl ester, acetoxymethyl benzylpenicillinate, and the development code WY-20788. It has been associated with the trade names Havapen and Maripen in historical pharmaceutical literature.
Penamecillin is structurally related to benzylpenicillin. Its chemical structure contains the characteristic beta-lactam ring and thiazolidine ring of penicillin derivatives, together with an acetoxymethyl ester group.
Its systematic chemical name is:
Acetyloxymethyl (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
PubChem confirms three defined stereocenters and the molecular formula C19H22N2O6S.
Penamecillin itself functions primarily as a prodrug of benzylpenicillin. Following administration, esterases hydrolyze the acetoxymethyl ester portion of the molecule, releasing benzylpenicillin. ChEBI specifically defines penamecillin as the acetoxymethyl ester of benzylpenicillin and identifies it as a prodrug for benzylpenicillin.
The resulting benzylpenicillin exerts its antibacterial action by interfering with bacterial cell-wall synthesis. Like other penicillin-class beta-lactam antibiotics, benzylpenicillin acts on bacterial penicillin-binding proteins and disrupts peptidoglycan cross-linking, ultimately compromising bacterial cell-wall integrity.
This prodrug approach was designed to modify the pharmaceutical and absorption characteristics of the parent penicillin.
Penamecillin has been studied as an orally active antibacterial prodrug. Historical pharmacological research investigated its absorption, metabolism and conversion to benzylpenicillin. PubChem classifies it as an antibacterial drug and prodrug, while ChEMBL records pharmaceutical development information for the compound.
Historical literature reports that penamecillin was investigated in relation to oral administration and systemic exposure to benzylpenicillin. It has also been studied in pharmacokinetic research involving the passage of penicillins from mother to fetus.
Because penamecillin is a historical/less commonly used penicillin prodrug rather than a widely marketed contemporary API, its current public regulatory specification information is considerably more limited than that available for major penicillins such as benzylpenicillin, amoxicillin or ampicillin.
Penamecillin is reported as a crystalline solid. Multiple chemical-reference sources report a melting point of approximately 106–108°C.
Historical chemical data also report a specific optical rotation of approximately:
[α]D20 +154°
This value is useful as a physicochemical reference but should not automatically be represented as a current pharmacopoeial acceptance range.
The compound has a calculated XLogP3 value of approximately 2.1, one hydrogen-bond donor, seven hydrogen-bond acceptors and eight rotatable bonds according to PubChem.
Public commercial/research sources provide limited and inconsistent quantitative solubility data for Penamecillin. One research supplier reports solubility of approximately 10 mM in DMSO, while other sources do not provide a validated aqueous solubility value.
For this reason, a universal numerical water-solubility specification should not be invented for the CMS API specification.
Penamecillin is available from research-chemical sources with different batch-specific purity specifications. For example, one commercial research listing reports 99.98% assay/purity, while another commercial source lists material at 96%. These differences demonstrate why commercial research-grade purity should not be presented as a universal pharmaceutical API specification.
Suitable analytical characterization of Penamecillin can include:
A commercial research source specifically provides RP-HPLC, NP-HPLC, LC-MS, MS, IR and other analytical documentation for its Penamecillin material.
For pharmaceutical or analytical development, important Penamecillin quality attributes can include:
However, no current public USP, Ph. Eur. or IP universal Penamecillin API monograph with numerical release limits was verified during this research. Therefore, numerical values such as assay limits, LOD, residue on ignition, heavy-metal limits and impurity limits should not be fabricated.
Penamecillin is directly related to benzylpenicillin. Its role is to act as an esterified prodrug that can release benzylpenicillin after enzymatic hydrolysis. The parent drug benzylpenicillin is an established beta-lactam antibacterial, whereas penamecillin represents an esterified form developed to modify pharmaceutical properties.
This relationship makes Penamecillin relevant to:
Potential applications of Penamecillin API or reference material include:
Because Penamecillin is not supported by a current publicly verified universal pharmacopoeial API specification, its final pharmaceutical quality requirements should be established from the applicable regulatory dossier, validated analytical procedures and approved product-specific specification.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.2% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | ≤ 1.5% |
| Melting Point | 106–108°C |
| Solubility | 106–108°C |