Penam

Penam
	source ↗
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

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.⁴³ Consequently, penams are susceptible to acid- and base-catalyzed hydrolysis.¹⁴

References

Singh, Girija S.; Sudheesh, Siji (2013). "β-Lactams". Natural Lactones and Lactams. pp. 101–145. doi:10.1002/9783527666911.ch3. ISBN 978-3-527-33414-8.
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
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.
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. Bibcode:2016ACIE...55.5062H. doi:10.1002/anie.201600919. ISSN 1433-7851. PMID 26953809.

[:0-1] Singh, Girija S.; Sudheesh, Siji (2013). "β-Lactams". Natural Lactones and Lactams. pp. 101–145. doi:10.1002/9783527666911.ch3. ISBN 978-3-527-33414-8.

[:1-2] 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

[:2-3] 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.

[:3-4] 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. Bibcode:2016ACIE...55.5062H. doi:10.1002/anie.201600919. ISSN 1433-7851. PMID 26953809.

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