γ-Lactam analogues of carbapenems

Boyd, Donald B.; Foster, B. J.; Hatfield, Lowell D.; Hornback, William J.; Jones, Noel D.; Munroe, John E.; Swartzendruber, John K.

doi:10.1016/s0040-4039(00)84821-2

Cited by 53 publications

(18 citation statements)

References 8 publications

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“…Both lactivicin and phenoxyacetyl-lactivicin are active against clinically isolated penicillin-resistant Streptococcus pneumoniae strains [107]. Recent efforts to [85], 5.2 [86], 5.3 [87], 5.4 [88], 5.5 [89], 5.6 [90], 5.7 [91] and 5.8 [92]). (B) Examples of inactive compounds (5.9 [93,94], 5.10 [93,94], 5.11 [88], 5.12 [95,96], 5.13 [97], 5.14 [98], 5.15 [99] and 5.16 [100]).…”

Section: Lactivicinmentioning

confidence: 99%

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

et al. 2016

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Avibactam, which is the first non-β-lactam β-lactamase inhibitor to be introduced for clinical use, is a broad-spectrum serine β-lactamase inhibitor with activity against class A, class C, and, some, class D β-lactamases. We provide an overview of efforts, which extend to the period soon after the discovery of the penicillins, to develop clinically useful non-β-lactam compounds as antibacterials, and, subsequently, penicillin-binding protein and β-lactamase inhibitors. Like the β-lactam inhibitors, avibactam works via a mechanism involving covalent modification of a catalytically important nucleophilic serine residue. However, unlike the β-lactam inhibitors, avibactam reacts reversibly with its β-lactamase targets. We discuss chemical factors that may account for the apparently special nature of β-lactams and related compounds as antibacterials and β-lactamase inhibitors, including with respect to resistance. Avenues for future research including non-β-lactam antibacterials acting similarly to β-lactams are discussed.

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Section: Lactivicinmentioning

confidence: 99%

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

et al. 2016

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“…The stereocontrol is often unremarkable; however, compared with the more popular benzylidene analog 1a , the acetonide-protected variant 1b enhances the preference for functionalization from the convex face. 1,8,15 Given the potential importance of these synthons, surprisingly few variants of the hemiaminal linkage have been reported. 1 …”

Section: Introductionmentioning

confidence: 99%

Lithium Enolates Derived from Pyroglutaminol: Aggregation, Solvation, and Atropisomerism

et al. 2016

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Lithium enolates derived from protected pyroglutaminols were characterized by using 6Li, 13C, and 19F NMR spectroscopies in conjunction with the method of continuous variation. A mixture of tetrasolvated dimers and tetrasolvated tetramers in proportions depend on the steric demands of the hemiaminal protecting group, tetrahydrofuran concentration, and the presence or absence of an α-fluoro moiety. The high steric demands of the substituted bicyclo[3.3.0] ring system promote dimers to an unusual extent and allow solvents and atropisomers in cubic tetramers to be observed in the slow-exchange limit. Pyridine used as a 6Li chemical shift reagent proved useful in assigning solvation numbers.

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“…Air- and moisture-sensitive materials were manipulated under argon with standard glovebox, vacuum line, and syringe techniques. Pyroglutaminol derivatives 1a and 1b were prepared by using literature methods …”

Section: Methodsmentioning

confidence: 99%

Lithium Enolates Derived from Pyroglutaminol: Mechanism and Stereoselectivity of an Azaaldol Addition

et al. 2016

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A lithium enolate derived from an acetonide-protected pyroglutaminol undergoes a highly selective azaaldol addition with (E)–N–phenyl–1–[2–(trifluoromethyl)phenyl]methanimine. The selectivity is sensitive to THF concentration, temperature, and the presence of excess lithium diisopropylamide base. Rate studies show that the observable tetrasolvated dimeric enolate undergoes reversible deaggregation, with the reaction proceeding via a disolvated-monomer-based transition structure. Limited stereochemical erosion stems from the intervention of a trisolvated-monomer-based pathway, which is suppressed at low THF concentrations and elevated temperature. Endofacial selectivity observed with excess lithium diisopropylamide (LDA) is traced to an intermediate dianion formed by subsequent lithiation of the monomeric azaaldol adduct, which is characterized as both a dilithio form and a trilithio dianion–LDA mixed aggregate.

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γ-Lactam analogues of carbapenems

Cited by 53 publications

References 8 publications

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

The Road to Avibactam: The First Clinically Useful Non-β-Lactam Working Somewhat Like a β-Lactam

Lithium Enolates Derived from Pyroglutaminol: Aggregation, Solvation, and Atropisomerism

Lithium Enolates Derived from Pyroglutaminol: Mechanism and Stereoselectivity of an Azaaldol Addition

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