Synthesis of 3-(3,4-dihydroxyphenyl)-propionic acid derivatives by N-coupling of amines using laccase

Mikolasch, Annett; Hammer, Elke; Jonas, Ulrike; Popowski, Katrin; Stielow, Anne; Schauer, Frieder

doi:10.1016/s0040-4020(02)00872-4

Cited by 82 publications

(53 citation statements)

References 14 publications

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“…Reaction kinetics similar to these findings were described for hybrid dimer formation from 3,4-dichloroaniline and syringic acid 24) or 3-(3,4-dihydroxy-phenyl)-propionic acid and 4-aminobenzoic acid. 25) In contrast, for hybrid dimer formation from 2,5-dihydroxybenzoic acid derivatives with aminopenicillins and aminocephalosporins, 2,3) amino acids, 26) and primary aromatic amines, 27,28) we found straightforward biotransformations. Therefore the amination of 2,5-dihydroxybenzoic acid derivatives with laccase from Trametes sp.…”

Section: Resultsmentioning

confidence: 78%

“…These reactions represent new, low-cost processes, which allow the use of mild reaction conditions, aqueous solvent systems, normal pressure, and room temperature. Further advantage is the specificity of the reaction, which can comprise the amination of para-and ortho-dihydroxylated aromatic compounds 2,3,25,27,28) on one hand and the combination of two antibiotics containing a phenol moiety, 38) the introduction of a phenolic compound into an antibiotic containing a phenolic moiety, 39) and the oxidation of an antibiotic 40) on the other hand. In summary it can be concluded that the laccase has a high potential for the synthesis of new antibiotic substances.…”

Section: 3)mentioning

confidence: 99%

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Novel .BETA.-Lactam Antibiotics Synthesized by Amination of Catechols Using Fungal Laccase

et al. 2008

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In preceding papers, we discussed the laccase-catalyzed amination of 2,5-dihydroxybenzoic acid derivatives with aminopenicillins and aminocephalosporins.2,3) The motive for our work was the global issue with resistant pathogenic bacteria, e.g. Streptococcus pneumoniae strains [4][5][6][7] and Staphylococcus strains, against currently available b-lactam antibiotics. [8][9][10][11] Aminated products like 2-(3,6-dioxocyclohexa-1,4-dienylamino)-2-phenyl-acetylamino-penicillanic acids and 2-(3,6-dioxocyclohexa-1,4-dienylamino)-2-phenyl-acetylamino-cephalosporanic acids 2,3) inhibited the growth of several Gram positive bacterial strains and protected mice against an infection with Staphylococcus aureus. After amination the 2,5-dihydroxybenzoic acid derivatives were units of the C-7 substituent of the b-lactam antibiotics.The possibility of utilizing catechol units as an element of the C-7 substituent of penicillins and cephalosporins was investigated for a long time. [12][13][14][15][16][17] Through the tonB dependent iron transport mechanism, 18) the use of catechol substituted b-lactams was known to increase the drug's penetration into the bacterial cell walls. Thus, several catechol-substituted blactams have been synthesized and showed good antimicrobial activities. [19][20][21][22][23] As a consequence of the promising activity of the catechol substituted b-lactams on one hand and the novel laccase-synthesized b-lactams on the other hand, we got interested in laccase-catalyzed amination of catechols with aminopenicillins and aminocephalosporins.In this study, we have employed laccase from Trametes sp. to derivatize amino-b-lactams and to couple them both with catechol and with substituted catechols. The novel b-lactams were structurally characterized as new coupling products inhibiting the growth of several Gram positive bacterial strains in the agar diffusion assay, among them methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. The cytotoxicity of the new compounds and the effectiveness in a "Staphylococcus-infected, immune suppressed mouse" model are discussed. Results and DiscussionBiotransformation of Amino-b b-lactams by LaccasesLaccase-catalyzed reaction between catechols (substrates 1a to 1c) on one hand and the amino-b-lactams cefadroxil 2a, amoxicillin 2b, ampicillin 2c, and the structurally related carbacephem loracarbef 2d on the other hand led to cross coupled products (Table 1). 3-Methylcatechol and amino-b-lactams were consumed after an incubation time of 1.5 h, and monoaminated products (3a to 3d) were detectable by high-performance liquid chromatography (HPLC). If other catechols or longer reaction times were used, monoaminated products were only obtained in low yields and undesirable side reactions produced a number of by-products. Reaction kinetics similar to these findings were described for hybrid dimer formation from 3,4-dichloroaniline and syringic acid 24) or 3-(3,4-dihydroxy-phenyl)-propionic acid and 4-aminobenzoic acid. 25) In contrast, for hybrid dimer form...

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Section: Resultsmentioning

confidence: 78%

Section: 3)mentioning

confidence: 99%

Novel .BETA.-Lactam Antibiotics Synthesized by Amination of Catechols Using Fungal Laccase

et al. 2008

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“…In contrast to these findings are reaction kinetics which were described for the coupling reaction between 3,4-dichloroaniline and syringic acid 22) and between 3-(3,4-dihydroxy-phenyl)-propionic acid and 4-aminobenzoic acid. 21) In these experiments the formation of byproducts diminished the yield of the coupling product up to 40%. The dihydroxylated compounds used in this study showed fast reactions in the control experiments without a second coupling partner, too.…”

Section: Resultsmentioning

confidence: 83%

“…Some years ago we found comparable straightforward biotransformation providing coupling products between 2,5-dihydroxybenzoic acid derivatives and primary aromatic amines 19,20) or b-lactam antibiotics, 1,2) as well as between 3-(3,4-dihydroxy-phenyl)-propionic acid and 1-hexylamine. 21) In all these reactions transformation rates and product yields are rather high and byproducts could be neglected. In contrast to these findings are reaction kinetics which were described for the coupling reaction between 3,4-dichloroaniline and syringic acid 22) and between 3-(3,4-dihydroxy-phenyl)-propionic acid and 4-aminobenzoic acid.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of New N-Analogous Corollosporine Derivatives with Antibacterial Activity by Laccase-Catalyzed Amination

Mikolasch

Hessel

Salazar

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Corollosporine isolated from the marine fungus Corollospora maritima and N-analogous corollosporines are antimicrobial substances. Owing to the basic structure of the N-analogous corollosporines, they have become an attractive target for laccase-catalyzed derivatisation. In this regard we report on the straightforward laccase-catalyzed amination of dihydroxylated arenes with N-analogous corollosporines. In biological assays the obtained amination products are more active than the parent compounds.

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“…[11][12][13] Recently we reported about our synthetic results on coupling reactions with laccase. [14][15][16][17] Now we have employed laccase to achieve derivatisation of b-lactam antibiotics and to couple them with derivatives of 2,5-dihydroxybenzoic acid. These derivatives are structurally related to the ganomycins, a new chemical class of antibacterial compounds 18) and to other antibacterial active isolates 19,20) therefore interesting as coupling partner for b-lactams using laccase as initiator of the reaction to produce novel hybridantibiotics by biotransformation.…”

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Novel Penicillins Synthesized by Biotransformation Using Laccase from Trametes spec.

et al. 2006

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There is an urgent need to develop new antimicrobial agents due to increasing bacterial resistance to therapeutically used drugs. Most methicillin-resistent Staphylococcus aureus (MRSA) strains are resistent not only to b-lactams, but also to most other antimicrobial agents.1) Penicillin resistance among Streptococcus pneumoniae strains is widely accepted as a global problem. [2][3][4][5] Bacteria have developed several strategies for escaping the lethal action of b-lactams. It may be expected that specific circumstance will make one the more effective stragegy than the other. 6) Much effort has been devoted to the discovery of drugs which would not be cleaved by b-lactamases of pathogenic strains and which have suitable physicochemical and pharmacodynamic profiles. 7,8) The modifications of b-lactam antibiotics could not keep pace with the development of resistance in the pathogenic microorganisms, so that numerous bacteria, among them multidrug resistant Staphylococcus strains, can no longer be treated with the currently available b-lactam antibiotics. 1,9,10) Besides the modification of existing antibiotics by chemical or biochemical methods the coupling of presently used antibiotics with other bioactive compounds or components from them which are not in use till now is a promising way to generate novel molecules with improved therapeutic properties.Laccase (benzenediol:oxygen oxidoreductase, EC 1.10.3.2), classically considered a hydroquinone oxidizing enzyme, is able to oligomerize molecules. Up to now main application fields of this enzyme are waste detoxification, textile dye transformation, biosensors and diagnostic application, where the capability to catalyze polymerization reactions is used. 11-13)Recently we reported about our synthetic results on coupling reactions with laccase.14-17) Now we have employed laccase to achieve derivatisation of b-lactam antibiotics and to couple them with derivatives of 2,5-dihydroxybenzoic acid. These derivatives are structurally related to the ganomycins, a new chemical class of antibacterial compounds 18) and to other antibacterial active isolates 19,20) therefore interesting as coupling partner for b-lactams using laccase as initiator of the reaction to produce novel hybridantibiotics by biotransformation.The use of laccase for the derivatisation of antibiotics is limited to a few examples including the phenolic oxidation of 7-(4-hydroxyphenylacetamido)cephalosporinic acid, 21) the dimerization of penicillin X 22) and the oxidative coupling of hydroquinone and mithramicine. 23) In the examples realized to date, the sought object of enhancement of the bioactive effect has not been achieved. 21-23)The aim of this study was (i) to investigate whether laccase can be used for the synthesis of novel penicillins by heteromolecular coupling of two different compounds, (ii) to characterize the products of the reaction, and (iii) to analyze the biological activity of the novel penicillins. Results and DiscussionBiotransformation of Amoxicillin and Ampicillin by Laccase of Tr...

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Synthesis of 3-(3,4-dihydroxyphenyl)-propionic acid derivatives by N-coupling of amines using laccase

Cited by 82 publications

References 14 publications

Novel .BETA.-Lactam Antibiotics Synthesized by Amination of Catechols Using Fungal Laccase

Novel .BETA.-Lactam Antibiotics Synthesized by Amination of Catechols Using Fungal Laccase

Synthesis of New N-Analogous Corollosporine Derivatives with Antibacterial Activity by Laccase-Catalyzed Amination

Novel Penicillins Synthesized by Biotransformation Using Laccase from Trametes spec.

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