The Total Synthesis of Penicillin V

Sheehan, John C.; Henery-Logan, Kenneth R.

doi:10.1021/ja01521a044

Cited by 157 publications

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“…Our goal was to justify the exclusive formation of the a-epimers 13 and 15. The thermodynamically most stable forms for compounds 13,15,23, and 24 are shown in Figure 1. We found that the distance between the lactam carbonyl oxygen and the carboxyl oxygen atoms in the b-epimer 23 was 3.69 (see Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…It should be noted that our synthetic b-lactams were in a racemic form, whereas natural b-lactam antibiotics are single stereoisomers. [15] Thus, only one half of the minimum inhibitory or protective concentrations would be necessary for each of the desired single enantiomer of 13 ± 16.…”

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confidence: 99%

“…), and Klebsiella pneumoniae (K. p.). These values were obtained by use of an agar dilution method whereby organisms were deposited onto medicated agar plates by the replication device of Steers et al [15] [b] b-Lactamase-producing organism.…”

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Concept of Counterattack Reagents: Intramolecular Counterattack Strategy in the Synthesis of Biologically Active Isopenams

et al. 1999

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A novel strategy was developed for the synthesis of isopenams in high yields. The strategy involves use of the intramolecular counterattack process in the conversions of (AE)-5 3(AE)-11, (AE)-6 3(AE)-12, and (AE)-19 3(AE)-11. Catalytic hydrogenation of (AE)-11 afforded isopenam (AE)-13, which possessed notable antimicrobial activities. Oxidation of (AE)-13 with KMnO 4 gave sulfone (AE)-15, which functioned as a potent inhibitor of various bacterial blactamases. Sulfone (AE)-15 exerted a great synergistic effect on antimicrobial agent (AE)-13. Results from the CVFF calculations of the C-2 b-epimer of isopenam 13 (i.e., 23) and the corresponding sulfone derivative 24 indicate the existence of a severe electronic repulsion between the b-lactam carbonyl and the C-2 carboxyl groups. Steric interaction also exists between the C-6 amide side chain and the C-2 carboxylic acid moiety in 23 and 24. These interactions, however, do not exist in the corresponding a-epimers 13 and 15.

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Section: Resultsmentioning

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Concept of Counterattack Reagents: Intramolecular Counterattack Strategy in the Synthesis of Biologically Active Isopenams

et al. 1999

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“…Deuteriobenzyl-d7-penicillin-The semisynthetic procedure of Sheehan and Henery-Logan (16) was utilized to prepare the isotopically altered penicillin. Phenylacetyl-d7-chloride was prepared by reacting 1.36 g. (9.15 mmoles) deuteriophenylacetic-&acid (98 atom D) with 4.42 g. (37.2 mmoles) thionyl chloride in a 15-ml.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Biological Activity of Deuteriobenzyl-d7-penicillin

Laskar

Mrtek

1970

Journal of Pharmaceutical Sciences

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“…Sheehan published in 1957 the first total synthesis of a natural penicillin, penicillin V (Scheme 24.44) [196]. At the time of this synthesis it was believed that the instability of penicillin was due to the presence of the strained four-membered b-lactam ring.…”

Section: Classical Synthesesmentioning

confidence: 99%

The Chemistry of 2‐Azetidinones (β‐Lactams)

Alcaide¹,

Almendros²,

Luna³

2011

Modern Heterocyclic Chemistry

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The large number of recent reports on b-lactam chemistry demonstrates the increasing interest in this important class of compounds. Monocyclic b-lactams frequently serve as precursors for the synthesis of classical bicyclic b-lactam antibiotics. The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalization of the b-lactam nucleus as a stereocontrolling element. The discovery of nonclassical b-lactam antibiotics, such as monobactams and nocardicins, coupled with ever-growing new applications such as enzyme inhibition has triggered a renewed interest in the building of new monocyclic b-lactam derivatives. Besides the utility of b-lactams as biologically active agents, they are used as intermediates in a-and b-amino acid synthesis, as well as building blocks for alkaloids, heterocycles, taxoids and other types of compounds of biological and medicinal interest. Physicochemical Data Computational ChemistryTheoretical studies show that b-lactams are weaker bases, in the gas phase, than acyclic amides [1]. The attenuation of basicity upon cyclization is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect that is present in b-lactams but not in cyclic ketones. Ab initio calculations indicate that both b-lactams and acyclic amides are oxygen bases, but the gap between the oxygen and nitrogen intrinsic basicities is much smaller in the former due to the aforementioned cyclization effects. This decrease of the oxygen Modern Heterocyclic Chemistry, First Edition. Edited

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The Total Synthesis of Penicillin V

Cited by 157 publications

References 0 publications

Concept of Counterattack Reagents: Intramolecular Counterattack Strategy in the Synthesis of Biologically Active Isopenams

Concept of Counterattack Reagents: Intramolecular Counterattack Strategy in the Synthesis of Biologically Active Isopenams

Synthesis and Biological Activity of Deuteriobenzyl-d7-penicillin

The Chemistry of 2‐Azetidinones (β‐Lactams)

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