A Novel, Mild, and Facile Method To Prepare 6-Methylidene Penem Derivatives

Abé, Takao; Sato, Chisato; Ushirogochi, Hideki; Sato, Koichi; Takasaki, Tsuyoshi; Isoda, Takeshi; Mihira, Ado; Yamamura, Itsuki; Hayashi, Kazuhiko; Kumagai, Toshio; Tamai, Satoshi; Shiro, Motoo; Venkatesan, and Aranapakam M.; Mansour, Tarek S.

doi:10.1021/jo049880g

Cited by 22 publications

(12 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of particular interest in this study, another amido reagent, the thermally highly stable lithium diphenylamide (LiNPh 2 ), has shown promise in a range of synthetic transformations. As well as regioselective deprotonation reactions, [6][7][8][9][10] it has also been used in catalytic aldol reactions involving silyl enol ethers and aldehydes; [11,12] in elimination applications; [13,14] in metathetical reactions; [15][16][17][18][19][20][21][22][23][24][25][26][27] during the preparation of amino-containing carbenes, [28] and as an initiator in the polymerisation of methyl methacrylate. [29] utilised as the metallating agent.…”

Section: Introductionmentioning

confidence: 99%

Structural Elucidation of tmeda‐Solvated Alkali Metal Diphenylamide Complexes

et al. 2009

View full text Add to dashboard Cite

Lithium, sodium and potassium salts of diphenylamine have been prepared by using a deprotonative route and characterised in both, solid state (by X‐ray crystallography) and solution (by NMR spectroscopic studies). In each case the metal atom's coordination sphere is completed by coordination to the synthetically important co‐ligand N,N,N′,N′‐tetramethylethylenediamine (tmeda). Complexes 1 and 2 [{(tmeda)M(NPh2)}2] (M = Li for 1, Na for 2) can be prepared by treating 1 mol.‐equiv. of the parent amine with an equimolar quantity of nBuM and tmeda in hexane solution. In the solid state, 1 and 2 are essentially isostructural, being dimeric with a four‐atom M–N–M–N framework. The coordination sphere of each M atom is completed by a bidentate tmeda molecule. Complex 3 [{(tmeda)3/2K(NPh2)}2] has been prepared in a similar way to 1 and 2 except that benzylpotassium has been utilised as the metallating agent. In addition, 4 mol‐equiv. of tmeda is required to fully solubilise the heavy alkali metal amide mixture. In the solid state, 3 exists as a polymeric array of dinuclear K–N–K–N rings. Akin to 1 and 2, the K atom is coordinated to a bidentate tmeda molecule; however, each K atom is also bound to another tmeda molecule that acts as a monodentate bridge, thus producing the coordination polymer. Crystalline 1 and 2 are soluble in C6D6; hence, NMR spectroscopic studies could be performed. These show that the solid‐state structure appears to stay intact in arene solution. On the other hand, 3 is not soluble in C6D6; so solution studies have been performed in [D8]thf. These studies reveal that 3 readily looses tmeda during in‐vacuo isolation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

show abstract

Section: Introductionmentioning

confidence: 99%

Structural Elucidation of tmeda‐Solvated Alkali Metal Diphenylamide Complexes

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Indeed our experience has shown that charge and spin densities (q and ρ, respectively) calculated by using the B3LYP method are of sufficiently high quality to explain the reactivity of 2,2′,3,3′-tetraphenylbicyclopropenyl radical cations [restricted B3LYP/6-31G(p)], [63] the molecular geometries and electronic structure of the geminally diphenyl-substituted trimethylenemethane radical cation [64] and 1,4-diphenylcyclohexane-1,4-diyl radical cation (5 •+ ) [65] (UB3LYP/cc-pVDZ), and the classical and nonclassical radical ions derived from 7-benzhydrylidenenorbornene analogs, [66][67][68] in addition to other reactive intermediates of this type. [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84] RESULTS AND DISCUSSION σ*-π* Conjugation of silole…”

Section: Methodsmentioning

confidence: 99%

Density functional theory study of silole‐fused tetramethyleneethane biradicals with orbital interactions

Kano

Mizuno

Ikeda

2011

J of Physical Organic Chem

View full text Add to dashboard Cite

The geometries, energy gap between singlet and triplet states (S–T gap), electronic transitions, and molecular orbitals of the diphenyl derivative of the silole‐fused tetramethyleneethane (TME) (3,4‐dimethylenesilole) biradical 7•• were determined by using the density functional theory method at the unrestricted Becke, three‐parameter, Lee–Yang–Parr/cc‐pVDZ level. In a manner similar to that of the parent TME biradical, the S–T gap of 7•• is small. The wavelengths of electronic transitions of 37•• (λET = 450 nm) are calculated to be different from that of 17•• (λET = 673 nm). These differences are attributed to interactions between orbitals of the two allyl radical moieties, especially, the existence of double σ*–π* conjugation, that is, π*–σ*–π* conjugation, that takes place in the silole subunit. Copyright © 2011 John Wiley & Sons, Ltd.

show abstract

“…Reaction between (5R, 6S)-6-bromo-7-oxo-4-thia-1-azabicycloA C H T U N G T R E N N U N G (3.2.0)hept-2-ene-2-carbocylic acid 4-nitrobenzyl ester 7 and aldehydes 8 a-h followed by a reductive elimination/deprotection step produced penems 9 a-h with Z configuration [23] (Scheme 1). The desired 5,5-bicyclic aldehydes 8 a-h required for these transformations were synthesized by utilizing different methods as described previously.…”

mentioning

confidence: 99%

On the Absolute Configuration in 1,4‐Dihydrothiazepine Covalent Complexes Derived from Inhibition of Class A and C β‐Lactamases with 6‐Methylidene Penems

et al. 2007

Self Cite

View full text Add to dashboard Cite

Serine and metallo b-lactamases catalyze the hydrolysis of blactam rings in all classes of blactam antibiotics which is a major cause of bacterial resistance to b-lactam antibiotics. Bacterial resistance is addressed clinically by combining a b-lactamase inhibitor, such as clavulanic acid, sulbactam, or tazobactam, with a b-lactam antibiotic (amoxicillin or piperacilin). [1][2][3][4][5] Whereas this strategy is effective with the class A b-lactamase inhibitors, there is an urgent need to extend the spectrum of activity to the other classes of serine b-lactamases including the class C enzymes. [6][7][8] Recently, new promising inhibitors of class C b-lactamases such as NXL104, AVE1330A, and diaroylphosphates have been disclosed. [9][10][11] Reports from our laboratories on 6-methylidene penems as mechanism-based inhibitors of serine-reactive class A and C b-lactamases disclosed extensive structure-activity relationships with penems containing monocyclic, [12] [6,5]-bicyclic, [13,14] and [5,5,5]-tricyclic [15,16] heterocycles that adopt the Z configuration at the C6 position.The mode of action of penem inhibitors involves acylation by the catalytic serine residues followed by b-lactam ring opening and a sequence of transformations amounting to a remarkable 7-endo trig rearrangement reaction. Penems 1-3 [16][17][18][19][20][21][22] have been studied by a plethora of methods to establish the formation of the 1,4-dihydrothiazepine acyl-enzyme complex (Figure 1). The complex is stable to hydrolysis because of the displacement of water molecules. However, an issue concerns the absolute stereochemistry of the C7 moiety bearing the heterocyles. In dihydrothiazepine 4 bearing the methyltriazolyl heterocyle, the S-stereochemistry is evidenced by kinetic, [18][19][20] computational, and X-ray crystallographic studies [18,21,22] in class A and C enzymes. The dihydroimidazoA C H T U N G T R E N N U N G [2,1-c]oxazine thiazepine 5 exists as the R-isomer in the crystal structure of both SHV-1 and GC1 enzymes.[13] A novel hydrophobic p-p stacking interaction between the C7 heterocycle with Tyr105 in SHV-1 and Tyr224 in GC1 was revealed. Furthermore, calculated interaction energy differences between C7R and C7S isomers of eight 6-methylidene penems bearing [6,5]-fused bicyclic heterocycles favor the formation of the C7R over the C7S enantiomer in both class A and C enzymes (SHV-1, GC1) respectively. [14] Insights into the binding sites in SHV-1 and GC1 revealed a certain degree of flexibility involving displacement of Tyr105 (SHV-1) and Tyr224 (GC1) residues. In the enzyme complex structure with 5, the hydrophobic p-p stacking interactions with the [6,5]-fused imidazoA C H T U N G T R E N N U N G [2,1-c]oxazine ring was clearly evident, which indeed was the case for the other [6,5]-fused heterocycles that were evaluated by the calculated interaction energy method. [14] The [5,5,5]-tricyclic penem 3 rearranges to thiazepine 6 containing both R and S C7 configurations with 30 % and 70 % crystal occupancy, respectively (Figure 1) as ...

show abstract

A Novel, Mild, and Facile Method To Prepare 6-Methylidene Penem Derivatives

Cited by 22 publications

References 34 publications

Structural Elucidation of tmeda‐Solvated Alkali Metal Diphenylamide Complexes

Structural Elucidation of tmeda‐Solvated Alkali Metal Diphenylamide Complexes

Density functional theory study of silole‐fused tetramethyleneethane biradicals with orbital interactions

On the Absolute Configuration in 1,4‐Dihydrothiazepine Covalent Complexes Derived from Inhibition of Class A and C β‐Lactamases with 6‐Methylidene Penems

Contact Info

Product

Resources

About