A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

Decuyper, Lena; Piens, Nicola; Mincke, Jens; Bomon, Jeroen; Schrijver, Bert De; Mollet, Karen; Winter, Karel De; Desmet, Tom; D’hooghe, Matthias

doi:10.1039/c6ra08213k

Cited by 7 publications

(3 citation statements)

References 61 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet, convinced by the assets of biocatalysis and its implementation in organic synthesis, as was also demonstrated by our preliminary studies on the chemoenzymatic syntheses of biologically relevant azaheterocyclic compounds, , the enzymatic glucosylation of chemically prepared cis -3-hydroxy-β-lactams 8 , without affecting the sensitive four-membered ring system, is envisioned in the current work. In fact, enzymatic glycosylation of 3-hydroxy-β-lactams as challenging substrates based on their rigidity and steric bulk, has never been described before.…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Approach toward the Synthesis of 3-O-(α/β)-Glucosylated 3-Hydroxy-β-lactams

et al. 2018

Self Cite

View full text Add to dashboard Cite

Glycosylation significantly alters the biological and physicochemical properties of small molecules. β-Lactam alcohols comprise eligible substrates for such a transformation based on their distinct relevance in the chemical and medicinal community. In this framework, the unprecedented enzymatic glycosylation of the rigid and highly strained four-membered β-lactam azaheterocycle was studied. For this purpose, cis-3-hydroxy-β-lactams were efficiently prepared in three steps by means of a classical organic synthesis approach, while a biocatalytic step was implemented for the selective formation of the corresponding 3-O-α- and -β-glucosides, hence overcoming the complexities typically encountered in synthetic glycochemistry and contributing to the increasing demand for sustainable processes in the framework of green chemistry. Two carbohydrate-active enzymes were selected based on their broad acceptor specificity and subsequently applied for the α- or β-selective formation of β-lactam-sugar adducts, using sucrose as a glucosyl donor.

show abstract

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Approach toward the Synthesis of 3-O-(α/β)-Glucosylated 3-Hydroxy-β-lactams

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…β-amino acids and amino alcohols. Thus, the stereoselective synthesis of the β-lactam moiety is an actively studied area [9][10][11][12][13][14][15]; in this paper we present a theoretical investigation on this subject.…”

Section: Introductionmentioning

confidence: 99%

“…There are several examples in the literature for the stereoselective synthesis of β-lactams; our research has been focused on the stereoselective Staudinger synthesis achieved by chiral auxiliaries [8,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. This reaction has been used to synthesize a wide variety of substituted β-lactam derivatives.…”

Section: Introductionmentioning

confidence: 99%

DFT Study of Stereoselective Ketene-imine Cycloadditions, Evaluation of Possible Solvent Effects with IEF-PCM

Komjáti

Szokol

Kováts

et al. 2018

Period. Polytech. Chem. Eng.

View full text Add to dashboard Cite

The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a facile method for the synthesis of biologically important β-lactam derivatives. In this paper two previously reported stereoselective reactions were investigated with computational methods. Our computations support experimental data that a chiral imine, derived from d-glyceraldehyde reacting with ketenes, yields almost exclusively one out of the possible four diastereomers. The reaction proceeds stepwise, first addition of the imine to the ketene yields an intermediate, then the product is formed in a conrotatory electrocyclization. Results indicate that the electrostatic repulsion of the chiral auxiliary group is the main factor of the stereoselectivity, but solvent and substituent effects are not negligible. Calculations were performed at M06-2X/6-31+G** level of theory combined with IEF-PCM solvation, in common solvents such as toluene, THF, dichloromethane, acetonitrile and water. These results provide useful insight for the development of new chiral auxiliaries and optimizing reaction parameters.

show abstract

Asymmetric Synthesis of β‐Lactams by theStaudinger Reaction

et al. 2018

View full text Add to dashboard Cite

In the century since Staudinger first reported the [2 + 2] cycloaddition reaction between a ketene and an imine to produce a β‐lactam, many variants, including highly stereoselective versions, have appeared that demonstrate a reliable and versatile transformation which has become the major synthetic entry to β‐lactams and products derived therefrom. Important advances have been made towards understanding the reaction mechanism, which in most cases is a stepwise process, as well as defining the variables which influence stereoselectivity. Successful diastereocontrol of the reaction can be achieved by using chiral auxiliaries attached at the ketene or the imine component, with diastereomeric ratios often above 95:5. Although most stereoselective methods afford β‐lactams with the 3,4‐ cis relative configuration, procedures to generate both monocyclic and bicyclic β‐lactams possessing the 3,4‐ trans configuration are also available. Whereas most current Staudinger protocols employ preformed imines, ketenes tend to be unstable and therefore are usually prepared in situ through dehydrohalogenation of acid chlorides by treatment with an excess of a tertiary amine base, or by in situ activation of carboxylic acids. Alternatively, stereoselective Staudinger reactions involving ketene generation by photolysis of Fisher chromium–carbene complexes or the Wolff rearrangement of α‐diazo carbonyl compounds are also viable. By this methodology stereoisomerically enriched β‐lactams can be prepared with a range of substitution patterns at the N1, C2, and C3 positions. The majority of the Staudinger reaction variants involve the synthesis of 3‐amino‐ and 3‐oxy‐β‐lactams, with fewer examples of 3‐halo‐, 3‐thio‐, or 3‐carbon‐substituted analogues. This chapter also describes applications of the Staudinger reaction to the synthesis of some important β‐lactam and non‐β‐lactam products.

show abstract

A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

Cited by 7 publications

References 61 publications

Chemoenzymatic Approach toward the Synthesis of 3-O-(α/β)-Glucosylated 3-Hydroxy-β-lactams

Chemoenzymatic Approach toward the Synthesis of 3-O-(α/β)-Glucosylated 3-Hydroxy-β-lactams

DFT Study of Stereoselective Ketene-imine Cycloadditions, Evaluation of Possible Solvent Effects with IEF-PCM

Asymmetric Synthesis of β‐Lactams by theStaudinger Reaction

Contact Info

Product

Resources

About