Synthesis of new phosphonamidate and phosphinamide desmuramyldipeptide analogs

Gobec, Stanislav; Urleb, U.

doi:10.1007/bf02443449

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…N -Acetylmuramic acid can also be replaced by various N -phthaloylated amino acids or phthalimido substituted aminoethoxyacetic acid (Figure 7) 128, 129 .…”

Section: Synthetic Approach Of Mdp Analogsmentioning

confidence: 99%

Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

Ogawa

Liu²,

Kobayashi³

2011

CBC

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Muramyl dipeptide (MDP) is a synthetic immunoreactive peptide consisting of N-acetyl muramic acid attached to a short amino acid chain of L-Ala-D-isoGln. It was first identified in bacterial cell wall peptidoglycan as an active component in Freund’s complete adjuvant. In the cell, MDP is detected by NOD2, a cytoplasmic receptor belonging to the human innate immune system. NOD2 mutations are frequently observed in patients with Crohn’s disease, an autoimmune disorder, suggesting the significance of the MDP-NOD2 pathway in activating immunity. For this reason, structural modifications of MDP and its derivatives have been extensively studied in an attempt to increase adjuvant activity and boost the immune response effectively for clinical use in the treatment of cancer and other diseases. This review summarizes the synthetic chemistry of MDP and its derivatives and discusses their pharmacological action and stereoselective synthesis.

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“…N -Acetylmuramic acid can also be replaced by various N -phthaloylated amino acids or phthalimido substituted aminoethoxyacetic acid (Figure 7) 128, 129 .…”

Section: Synthetic Approach Of Mdp Analogsmentioning

confidence: 99%

Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

Ogawa

Liu²,

Kobayashi³

2011

CBC

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“…However, in our hands phosphonamidate methyl ester 9 decomposed even during mild catalytic hydrogenation. We could observe similar decomposition during our efforts to either hydrolytically or acidolytically deprotect closely related phosphonamidate methyl esters, bearing methyl, ethyl or tert -butyl protection on the C-terminal D-Glu residue [ 19 ]. Hence, we can conclude that the stability of phosphonamide bond depends strongly on the chemical structure of phosphonamidate ester pseudopeptide under investigation.…”

Section: Resultsmentioning

confidence: 99%

“…To obtain more information about structure-activity relationships, we modified the peptide backbone of phthalimido desmuramyl dipeptides by introducing various phosphorus-containing species. We replaced the amide bond at the end of the acyclic side chain by phosphonamidate ethyl ester [ 18 ] and by the phosphinamide moiety [ 19 ]. We have also replaced the amide bond between Ala and Glu by phosphonamidate methyl ester [ 19 ], and the γ-carboxylic group of Glu by diethyl phosphonate isostere [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…We replaced the amide bond at the end of the acyclic side chain by phosphonamidate ethyl ester [ 18 ] and by the phosphinamide moiety [ 19 ]. We have also replaced the amide bond between Ala and Glu by phosphonamidate methyl ester [ 19 ], and the γ-carboxylic group of Glu by diethyl phosphonate isostere [ 20 ]. Stimulated by the results of preliminary immunological tests of selected phosphorus MDP analogues [ 17 ], we present the syntheses of three new phosphapeptides related to LK 423, whose amide bonds between L-alanyl and D-glutamate moieties are replaced by phosphonamidate and phosphonate bonds, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of New Lipophilic Phosphonate and Phosphonamidate Analogues of N-Acetylmuramyl-L-alanyl-D-isoglutamine Related to LK 423

Gobec

Urleb

2002

Molecules

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A syntheses of three new muramyl dipeptide (MDP) analogues related to LK 423 as potential immunomodulators are presented. The dipeptide part of the lead compound was modified by introducing a phosphonamide isostere instead of the amide bond between L-alanine and D-glutamic acid (or D-isoglutamine), yielding new MDP analogues 5 and 9. Furthermore, the amide bond between L-Ala and D-Glu was replaced by a phosphonate isostere, giving peptidyl phosphonate 14. The scope and limitations of the synthetic strategies employed are discussed.

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Modulation of cytokine production by some phthalimido-desmuramyl dipeptides and their cytotoxicity

et al. 2004

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Synthesis of new phosphonamidate and phosphinamide desmuramyldipeptide analogs

Abstract: New desmuramyldipeptide analogs with modified peptide backbones were synthesized. The peptide bond between Ala and Glu was replaced by a phosphonamidate methyl ester moiety. The amide bond at the end of the acyclic side chain was replaced by a phosphinamide moiety.

Cited by 3 publications

References 7 publications

Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

Muramyl Dipeptide and its Derivatives: Peptide Adjuvant in Immunological Disorders and Cancer Therapy

Synthesis of New Lipophilic Phosphonate and Phosphonamidate Analogues of N-Acetylmuramyl-L-alanyl-D-isoglutamine Related to LK 423

Modulation of cytokine production by some phthalimido-desmuramyl dipeptides and their cytotoxicity

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