Penam

Penam
Names

IUPAC name (5R)-4-thia-1-azabicyclo[3.2.0]heptan-7-one
Other names 1-Aza-7-oxo-4-thiabicyclo[3.2.0]heptane
Identifiers
CAS Number	53908-04-6^{N[ChemSpider]}
3D model (JSmol)	Interactive image
Beilstein Reference	4374479
ChEBI	CHEBI:35991^Y
ChemSpider	7827765
PubChem CID	9548842
InChI InChI=1S/C5H7NOS/c7-4-3-5-6(4)1-2-8-5/h5H,1-3H2/t5-/m1/s1 Key: WSHJJCPTKWSMRR-RXMQYKEDSA-N InChI=1S/C5H7NOS/c7-4-3-5-6(4)1-2-8-5/h5H,1-3H2/t5-/m1/s1 Key: WSHJJCPTKWSMRR-RXMQYKEDSA-N
SMILES C1CSC2N1C(=O)C2
Properties
Chemical formula	C₅H₇NOS
Molar mass	129.18 g·mol⁻¹
Related compounds
Related compounds	clavam
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Chemical compound

Penams are the primary skeleton structures that define the penicillin subclass of the broader β-lactam family of antibiotics and related compounds. They are bicyclic ring systems containing a β-lactam moiety fused with a five-member thiazolidine ring. ^[1] Due to ring strain and limitations on amide resonance, the structure is unstable and highly susceptible to catalytic cleavage at the amide bond.^[2] Benzylpenicillin (penicillin G) is the natural product parent that contains the penam structure.

Structure

Penams have inflexible structures. The structure is locked in a puckered (i.e. bent) shape due to the pyramidal geometry of the bridgehead nitrogen. The pyramidalization (χ = 54°) and twist of the C-N bond (τ = 18°) is caused by the strain from the lone pair's exclusion from planarity with the cyclic rings and electrostatic repulsion effects. As a result, the distorted C-N bond causes misalignment the orbitals of the carbonyl carbon and the nitrogen lone pair that allow for resonance overlap. The amide C-N bond length is 1.406 Å and displays greater single bond character than in noncyclic tertiary amides. The C-O bond length is 1.205 Å which is shorter than C-O bonds in noncyclic tertiary amides.^[3]

Penams are strained due to the angle strain on the four-member β-lactam ring, whose internal bond angles are 90º.^[4]^[3] Consequently, penams are susceptible to acid- and base-catalyzed hydrolysis.^[1]^[4]

References

^ ^a ^b Novak, Igor; Chua, Pei Juan (2006-09-01). "Computational Study of Pharmacophores: β-Lactams". The Journal of Physical Chemistry A. 110 (35): 10521–10524. Bibcode:2006JPCA..11010521N. doi:10.1021/jp063162b. ISSN 1089-5639. PMID 16942059.
^ Patrick, Graham (2017-03-23), "5. Pharmaceuticals and medicinal chemistry", Organic Chemistry: A Very Short Introduction, Oxford University Press, pp. 71–89, doi:10.1093/actrade/9780198759775.003.0005, ISBN 978-0-19-875977-5
^ ^a ^b Glover, Stephen A.; Rosser, Adam A. (2012-06-14). "Reliable Determination of Amidicity in Acyclic Amides and Lactams". The Journal of Organic Chemistry. 77 (13): 5492–5502. doi:10.1021/jo300347k. ISSN 0022-3263. PMID 22646836.
^ ^a ^b Hu, Feng; Lalancette, Roger; Szostak, Michal (2016-03-08). "Structural Characterization of N-Alkylated Twisted Amides: Consequences for Amide Bond Resonance and N−C Cleavage". Angewandte Chemie International Edition. 55 (16): 5062–5066. doi:10.1002/anie.201600919. ISSN 1433-7851. PMID 26953809.

Antibacterials active on the cell wall and envelope (J01C-J01D)

Beta-lactams
(inhibit synthesis
of peptidoglycan
layer of bacterial
cell wall by binding
to and inhibiting
PBPs, a group of
D-alanyl-D-alanine
transpeptidases)

Penicillins (Penams)

Narrow
spectrum

β-lactamase sensitive (1st generation)	Benzylpenicillin (G)^# Benzathine benzylpenicillin^# Procaine benzylpenicillin^# Phenoxymethylpenicillin (V)^# Propicillin^‡ Pheneticillin^‡ Azidocillin^‡ Clometocillin^‡ Penamecillin^‡
β-lactamase resistant (2nd generation)	Cloxacillin^# (Dicloxacillin Flucloxacillin) Oxacillin Nafcillin Methicillin^‡

Extended
spectrum

Aminopenicillins (3rd generation)	Amoxicillin^# Ampicillin^# (Pivampicillin Hetacillin^‡ Bacampicillin^‡ Lenampicillin Metampicillin^‡ Talampicillin^‡) Epicillin^‡
Carboxypenicillins (4th generation)	Ticarcillin Carbenicillin^‡ / Carindacillin^‡ Temocillin^‡
Ureidopenicillins (4th generation)	Piperacillin Azlocillin^‡ Mezlocillin^‡
Other	Mecillinam (Pivmecillinam) Sulbenicillin^‡

Carbapenems / Penems

Cephems
Cephalosporins
Cephamycins
Carbacephems

1st generation	Cefazolin^# Cefalexin ^# Cefadroxil Cefapirin Cefazedone^‡ Cefazaflur^‡ Cefradine^‡ Cefroxadine^‡ Ceftezole^‡ Cefaloglycin^‡ Cefacetrile^‡ Cefalonium^‡ Cefaloridine^‡ Cefalotin Cefatrizine^‡
2nd generation	Cefaclor Cefprozil Cefuroxime Cefuroxime axetil Cefamandole^‡ Cefonicid^‡ Ceforanide^‡ Cefuzonam^‡ Cephamycin (Cefoxitin Cefotetan Cefminox^‡ Cefbuperazone^‡ Cefmetazole^‡) Carbacephem (Loracarbef^‡)
3rd generation	Cefixime^# Ceftriaxone^# Cefotaxime^# Antipseudomonal (Ceftazidime^# Cefoperazone) Cefdinir Cefcapene Cefdaloxime Ceftizoxime Cefmenoxime Cefpiramide Cefpodoxime Ceftibuten Cefditoren Cefotiam^‡ Cefetamet^‡ Cefodizime^‡ Cefpimizole^‡ Cefsulodin^‡ Cefteram^‡ Ceftiolene^‡ Oxacephem (Flomoxef Latamoxef^‡)
4th generation	Cefepime Cefozopran^‡ Cefpirome Cefquinome^‡
5th generation	Ceftaroline fosamil Ceftolozane Ceftobiprole
Siderophore	Cefiderocol^#
Veterinary	Ceftiofur Cefquinome Cefovecin

Monobactams

β-lactamase inhibitors

Combinations

Polypeptides

Glycopeptides Lipoglycopeptides	Inhibit PG chain elongation: Vancomycin^# (Oritavancin Telavancin) Teicoplanin (Dalbavancin) Ristocetin^‡ Avoparcin Inhibit autolysin: Corbomycin (not approved)
Lipopeptides	Insert into bacterial cell wall causing perforation and depolarization: Daptomycin Surfactin
Polymyxins	Bind to LPS in the outer bacterial membrane, acting in detergent-like fashion: Colistin Polymyxin B
Other	Inhibits PG elongation and crosslinking: Ramoplanin^§