Preparation and some biological properties of N-acetylmuramyl-alanyl-D-isoglutamine (MDP) analogues

1982 ◽  
Vol 47 (11) ◽  
pp. 2989-2995 ◽  
Author(s):  
Milan Zaoral ◽  
Jan Ježek ◽  
Jiří Rotta
Keyword(s):  
Biological Properties ◽  
Benzyl Ester ◽  
Protecting Groups

The condensation of 1-α-O-benzyl-4,6-O-benzylidene-N-acetylgalactomuramic acid (I), 1-α-O-benzyl-4,6-O-benzylidene-N-acetylallomuramic acid (VIII), and 1-α-O-benzyl-4,6-O-benzylidene-N-acetylnorallomuramic acid (XI) with alanyl-D-isoglutamine benzyl ester afforded 1-α-O-benzyl-4,6-O-benzylidene-N-acetylgalactomuramyl-alanyl-D-isoglutamine benzyl ester (XII), 1-α-O-benzyl-4,6-O-benzylidene-N-acetylallomuramyl-alanyl-D-isoglutamine benzyl ester (XIII) and 1-α-O-benzyl-4,6-O-benzylidene-N-acetylnorallomuramyl-alanyl-D-isoglutamine benzyl ester (XIV). Protecting groups were removed from XII-XIV and N-acetylgalactomuramyl-alanyl-D-isoglutamine (XV), N-acetylallomuramyl-alanyl-D-isoglutamine (XVI), and N-acetylnorallomuramyl-alanyl-D-isoglutamine (XVII) were obtained. XV-XVII showed lower pyrogenic and immunoadjuvant effect than N-acetylmuramyl-alanyl-D-isoglutamine.

scholarly journals The Efficient Synthesis of Azasugars from Pentoses

2021 ◽  
Author(s):  
◽  
Michael Meijlink
Keyword(s):  
Clinical Trials ◽  
Biological Properties ◽  
Protecting Groups ◽  
Synthetic Route ◽  
Efficient Synthesis ◽  
Atom Economy ◽  
Total Syntheses ◽  
Structural Analogues ◽  
Original Procedure ◽  
Synthetic Routes

<p>Azasugars [e.g., 1-deoxy-aza-xylopyranose (1) Figure 1] are structural analogues of sugars [e.g., α-D-xylopyranose (2)] where the ring oxygen is substituted by a nitrogen atom. The resemblance of azasugars to their carbohydrate counterparts gives them various biological properties, such as the inhibition of glycosidase and glycosyltransferase enzymes, and as such, these compounds have been in clinical trials for the treatment of AIDS, diabetes,and cancer. Synthetic routes to azasugars have often involved the use of protecting groups, and therefore have generally reduced efficiency by requiring additional steps to apply or remove protecting groups or requiring adjustment of stereochemistry during the synthesis. This thesis presents the first example of a synthesis of four sterochemically different piperidine triols through a four-step methodology minimising the use of protecting groups starting from pentoses. The synthesis of D-xylose derived (3R,4r,5S)-piperidine triol was previously obtained in 40% yield over five steps, but was afforded in 45% overall yield over four steps using the methodology described within this thesis. Next, D-ribose derived (3R,4s,5S)-piperidine triol was obtained in 40% overall yield over four steps, which afforded a vast improvement on the previous most efficient synthetic route obtaining the azasugar in 24% yield over four steps. This four-step three-pot methodology has thus allowed for the synthesis of these piperidine triols in overall yields ranging from 4-69%, surpassing previous total syntheses in efficiency and improving overall atom economy. To further probe the applicability of the methodology, N-alkyl analogues (such as butyl-, phenylethyl-, and hydroxyethyl-analogues) of all four different piperidine triols were synthesised in comparable or greater overall yields compared to literature reports without any required adaptation to the original procedure. Included in these N-alkyl analogues are seven novel azasugars which were obtained in overall yields ranging from 6-35%.</p>

scholarly journals Syntheses of penicillin N, [6 α-3H]penicillin N and [10-14C,6 α-3H]penicillin N

1980 ◽  
Vol 186 (3) ◽  
pp. 881-887 ◽  
Author(s):  
J E Baldwin ◽  
S R Herchen ◽  
P D Singh
Keyword(s):  
Glutamic Acid ◽  
Benzyl Ester ◽  
Protecting Groups ◽  
Acid Salt ◽  
Schiff’S Base ◽  
Free Amine ◽  
Penicillanic Acid ◽  
Base Derivative

1. Penicillin N was synthesized by coupling alpha-amino-alpha-p-nitrobenzyl-N-p-nitro-benzyloxycarbonyl-D-adipate with 6-aminopenicillanic acid benzyl ester, followed by removal of the protecting groups through hydrogenolysis. 2. alpha-Amino-alpha-p-nitrobenzyl-N-p-nitrobenzyloxycarbonyl-D-[5-14C]adipate was prepared by treating alpha-p-nitrobenzyl-N-p-nitrobenzyloxycarbonyl-D-glutamic acid with [14C]diazomethane followed by rearrangement with silver trifluoromethanesulphonate. 3. Coupling of alpha-amino-alpha-p-nitrobenzyl-N-p-nitrobenzyloxycarbonyl-D-[5-14C]adipate with 6-aminopenicillanic acid benzyl ester gave triprotected [10-14C]penicillin N. 4. 3H was introduced at C-6 of the Schiff's base derivative (10) by oxidation followed by reduction with NaB3H4. 5. The so-derived (6 alpha-3H)-labelled Schiff's base was hydrolysed to give 6-amino [6 alpha-3H]penicillanic acid benzyl ester p-toluenesulphonic acid salt, which after coupling as the free amine with alpha-amino-alpha-p-nitrobenzyl-N-pnitrobenzyloxycarbonyl-D-adipate and then hydrogenolysis, yielded [6alpha-3H]penicillin N. 6. Triprotected [10-14C]penicillin N and triprotected [6alpha-3H]penicillin N in admixture were hydrogenolysed to give [10-14C,6alpha-3H]penicillin N.

Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates

1982 ◽  
Vol 60 (8) ◽  
pp. 976-980 ◽  
Author(s):  
Alenka Paquet
Keyword(s):  
Benzyl Ester ◽  
Protecting Groups ◽  
Efficient Conversion ◽  
Hydroxyamino Acids ◽  
High Yields ◽  
Derivatives Of ◽  
Acid Esters ◽  
Efficient Reagent

9-Fluorenylmethyl succinimidyl, pentachlorophenyl, and benzotriazole-1-yl carbonates were prepared and their reactivity with L-serine and L-serine benzyl ester was compared. The most efficient reagent, 9-fluorenylmethyl succinimidyl carbonate, was used for the preparation of 9-fluorenylmethyloxycarbonyl derivatives of other hydroxyamino acids and hydroxyamino acid esters in high yields. The use of trichloroethyl and benzyl succinimidyl carbonates for an efficient conversion of hydroxyamino acids and their esters into the corresponding N-trichloroethoxycarbonyl and benzyloxycarbonyl derivatives is described.

scholarly journals Aminated Graphene-Graft-Oligo(Glutamic Acid) /Poly(ε-Caprolactone) Composites: Preparation, Characterization and Biological Evaluation

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2628
Author(s):  
Mariia Stepanova ◽  
Olga Solomakha ◽  
Maxim Rabchinskii ◽  
Ilia Averianov ◽  
Iosif Gofman ◽  
...  
Keyword(s):  
Composite Materials ◽  
Glutamic Acid ◽  
Polymer Matrix ◽  
Photoelectron Spectroscopy ◽  
Ring Opening ◽  
Soft Tissues ◽  
Biological Properties ◽  
Biological Evaluation ◽  
Benzyl Ester ◽  
X Ray

Biodegradable and biocompatible composites are of great interest as biomedical materials for various regeneration processes such as the regeneration of bones, cartilage and soft tissues. Modification of the filler surface can improve its compatibility with the polymer matrix, and, as a result, the characteristics and properties of composite materials. This work is devoted to the synthesis and modification of aminated graphene with oligomers of glutamic acid and their use for the preparation of composite materials based on poly(ε-caprolactone). Ring-opening polymerization of N-carboxyanhydride of glutamic acid γ-benzyl ester was used to graft oligomers of glutamic acid from the surface of aminated graphene. The success of the modification was confirmed by Fourier-transform infrared and X-ray photoelectron spectroscopy as well as thermogravimetric analysis. In addition, the dispersions of neat and modified aminated graphene were analyzed by dynamic and electrophoretic light scattering to monitor changes in the characteristics due to modification. The poly(ε-caprolactone) films filled with neat and modified aminated graphene were manufactured and carefully characterized for their mechanical and biological properties. Grafting of glutamic acid oligomers from the surface of aminated graphene improved the distribution of the filler in the polymer matrix that, in turn, positively affected the mechanical properties of composite materials in comparison to ones containing the unmodified filler. Moreover, the modification improved the biocompatibility of the filler with human MG-63 osteoblast-like cells.

scholarly journals Crystal structure of Boc-(S)-ABOC-(S)-Ala-(S)-ABOC-(S)-Phe-OBn chloroform monosolvate

2015 ◽  
Vol 71 (10) ◽  
pp. 1193-1195
Author(s):  
Emmanuel Wenger ◽  
Laure Moulat ◽  
Baptiste Legrand ◽  
Muriel Amblard ◽  
Monique Calmès ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Carboxylic Acid ◽  
Hydrogen Bonds ◽  
Benzyl Ester ◽  
Protecting Groups ◽  
Amino Acid Residues ◽  
Hybrid Peptide ◽  
Proteinogenic Amino Acid ◽  
Solvent Molecules

In the title compound, phenyl (S)-2-[(S)-(1-{2-[(S)-(1-{[(tert-butoxy)carbonyl]amino}bicyclo[2.2.2]octan-2-yl)formamido]propanamido}bicyclo[2.2.2]octan-2-yl)formamido]-3-phenylpropanoate chloroform monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S)-1-aminobicyclo[2.2.2]octane-2-carboxylic acid [(S)-ABOC], two amino acid residues of (S)-2-aminopropanoic acid [(S)-Ala] and (S)-2-amino-3-phenylpropanoic acid [(S)-Phe], and protecting groups oftert-butoxycarbonyl (Boc) and benzyl ester (OBn). The tetramer folds into a right-handed mixed 11/9 helix stabilized by intramoleculari,i + 3 andi,i − 1 C=O...H—N hydrogen bonds. In the crystal, the oligomers are linked by N—H...O=C hydrogen bonds into chains along thea-axis direction. The chloroform solvent molecules are intercalated between the folded chainsviaC—H...O=C interactions.

A convenient preparative method for tryptophan benzyl esters

1975 ◽  
Vol 28 (9) ◽  
pp. 2065 ◽  
Author(s):  
K Williams ◽  
B Halpern
Keyword(s):  
Amino Acid ◽  
Catalytic Hydrogenation ◽  
Synthetic Peptide ◽  
Preparative Method ◽  
Benzyl Ester ◽  
Protecting Groups ◽  
Benzyl Esters

The utilization of amino acid benzyl esters in synthetic peptide procedures offers advantages over the corresponding methyl or ethyl derivatives. Whereas the latter groups must by cleaved by alkaline saponification, the benzyl ester function can be removed by acidolysis or by catalytic hydrogenation under conditions which permit the simultaneous cleavage of N-acyl-protecting groups such as t-Boc or CBzl.*

scholarly journals Synergy of Hydeal-D® and Hyaluronic Acid for Protecting and Restoring Urothelium: In Vitro Characterization

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1450
Author(s):  
Marco Ruggeri ◽  
Mauro Pavan ◽  
Matteo Soato ◽  
Susi Panfilo ◽  
Carlo Barbera ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Ex Vivo ◽  
Active Role ◽  
Biological Properties ◽  
Benzyl Ester ◽  
Bladder Pain ◽  
In Vitro Characterization ◽  
Painful Bladder ◽  
Anti Inflammatory

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim of this work was the in vitro characterization of biological properties (mucoadhesion and anti-inflammatory activity) of a commercial product (HydealCyst–HydC) based on hyaluronic acid (HA) and the benzyl ester of HA (Hydeal-D®) intended for bladder instillation to restore and/or protect the urothelial layer of glycosamino glycans (GAGs). The in vitro characterization demonstrated that an interaction product is formed between HA and Hydeal-D® that has a role in the rheological behavior and mucoadhesive properties. HA was identified as a key component to form the mucoadhesive joint, while the interaction of HA with Hydeal-D® improved polysaccharide stability and prolonged the activity ex vivo. Moreover, HydC is cytocompatible with urothelial cells (HTB-4) and possesses an anti-inflammatory effect towards these cells by decreasing the secretion of IL-6 and IL-8, which were both increased in patients with IC, and by increasing the secretion of sulfated GAGs. These two findings, along with the resilience properties of the formulation due to mucoadhesion, suggest the active role of HydC in protecting and restoring urothelium homeostasis.

Pd/charcoal-catalysed cleavage of benzyl ester protecting groups in poly(benzyl acrylate) and poly(benzyl methacrylate)

Polymer ◽  
1991 ◽  
Vol 32 (14) ◽  
pp. 2659-2665 ◽  
Author(s):  
A. Caron ◽  
C. Bunel ◽  
C. Braud ◽  
M. Vert
Keyword(s):  
Benzyl Ester ◽  
Protecting Groups

scholarly journals The Efficient Synthesis of Azasugars from Pentoses

2021 ◽  
Author(s):  
◽  
Michael Meijlink
Keyword(s):  
Clinical Trials ◽  
Biological Properties ◽  
Protecting Groups ◽  
Synthetic Route ◽  
Efficient Synthesis ◽  
Atom Economy ◽  
Total Syntheses ◽  
Structural Analogues ◽  
Original Procedure ◽  
Synthetic Routes

<p>Azasugars [e.g., 1-deoxy-aza-xylopyranose (1) Figure 1] are structural analogues of sugars [e.g., α-D-xylopyranose (2)] where the ring oxygen is substituted by a nitrogen atom. The resemblance of azasugars to their carbohydrate counterparts gives them various biological properties, such as the inhibition of glycosidase and glycosyltransferase enzymes, and as such, these compounds have been in clinical trials for the treatment of AIDS, diabetes,and cancer. Synthetic routes to azasugars have often involved the use of protecting groups, and therefore have generally reduced efficiency by requiring additional steps to apply or remove protecting groups or requiring adjustment of stereochemistry during the synthesis. This thesis presents the first example of a synthesis of four sterochemically different piperidine triols through a four-step methodology minimising the use of protecting groups starting from pentoses. The synthesis of D-xylose derived (3R,4r,5S)-piperidine triol was previously obtained in 40% yield over five steps, but was afforded in 45% overall yield over four steps using the methodology described within this thesis. Next, D-ribose derived (3R,4s,5S)-piperidine triol was obtained in 40% overall yield over four steps, which afforded a vast improvement on the previous most efficient synthetic route obtaining the azasugar in 24% yield over four steps. This four-step three-pot methodology has thus allowed for the synthesis of these piperidine triols in overall yields ranging from 4-69%, surpassing previous total syntheses in efficiency and improving overall atom economy. To further probe the applicability of the methodology, N-alkyl analogues (such as butyl-, phenylethyl-, and hydroxyethyl-analogues) of all four different piperidine triols were synthesised in comparable or greater overall yields compared to literature reports without any required adaptation to the original procedure. Included in these N-alkyl analogues are seven novel azasugars which were obtained in overall yields ranging from 6-35%.</p>

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